2015-04-22
2015-04-21
Fertilidad después de cáncer: opción o temeridad?
Conferencia impartida en el Hotel InterContinental de Medellín en el marco de los 20 años de InSER, en 16/04/2015.
2015-02-04
2015-01-25
Highlights of the 2015 ASCO GI Cancer Symposium
Based on CancerNetwork.
MM-398 (A Liposomal Irinotecan) + 5-FU/Leucovorin improves survival in patients with pancreatic cancer previously treated with gemcitabine.
1. MM-398 Combo Shows Benefit in Metastatic Pancreatic Cancer: Li-Tzong Chen, MD, PhD, presenting results from the phase III NAPOLI-1 trial, which found that combining MM-398 with 5-FU/leucovorin chemotherapy in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy resulted in improved survival compared with 5-FU/leucovorin alone. The overall survival analysis showed an advantage for patients taking the combination MM-398 plus 5-FU/leucovorin (6.1 months vs 4.2 months; stratified hazard ratio [HR] = 0.57; P = .0009). There was no significant survival advantage for patients assigned MM-398 alone compared with 5-FU/leucovorin alone.
Some patients with stage I-III rectal cancer MAY avoid surgery
2. Low-Risk Group Can Avoid Surgery for Locally Advanced Rectal Cancer: A retrospective analysis of 145 stage I–III rectal cancer patients shows that those patients who have a complete response after chemoradiotherapy and chemotherapy had a similar 4-year survival rate regardless of whether they had surgery or opted for surveillance. In general, about 40% of patients with stage I–III disease have disappearance of their tumors after systemic therapy. The 4-year overall survival rate was 91% and 95% in the no surgery and standard surgery groups, respectively. There was no difference in the rate of distant recurrences between the two groups. “These data continue to suggest that non-operative management does not compromise oncologic outcome, and that preservation of the rectum is achieved in a majority of patients,” concluded the authors.
Second-line Ramucirumab benefit restricted to elevated AFP levels in patients with hepato-cellular carcinoma
3. Baseline AFP Levels Affect Ramucirumab Benefit in HCC: Andrew X. Zhu, MD, PhD, of Massachusetts General Hospital Cancer Center, presenting results from the phase III REACH study, which found that alpha-fetoprotein (AFP) levels could serve as a prognostic indicator in advanced hepatocellular carcinoma (HCC) patients treated with second-line ramucirumab. Treatment with ramucirumab resulted in a significant survival advantage for patients with a baseline AFP level of 400 ng/mL or greater (7.8 months vs 4.2 months; HR = 0.674; P = .0059). The drug did not confer a survival advantage among patients with lower baseline AFP levels (10.1 months vs 11.8 months).
AMG-337, a MET Inhibitor, highly active in patients with MET-amplified gastroesophageal tumors
4. Small Molecule MET Inhibitor Active in Gastroesophageal Cancer: Of the 13 patients with MET-amplified tumors treated once daily with AMG-337, a small molecule MET inhibitor, 8 had a partial or near complete response. AMG-337 is a potent and selective inhibitor that targets both wild-type and some mutant forms of MET. The subset of patients with MET-amplified gastroesophageal junction, gastric, and esophageal cancers responded to treatment. One responder had tumor shrinkage of more than 90%. Based on these phase I results, a phase II trial in MET-amplified gastroesophageal junction, gastric, and esophageal cancers is currently ongoing.
Minimally invasive esophagectomy affords less short-term morbidity in phase III trial
5. Minimally Invasive vs Open Esophagectomy in Esophageal Cancer: Christophe Mariette, MD, PhD, of the department of digestive and oncologic surgery, Claude Huriez University Hospital, presenting data from the phase III MIRO study that compared hybrid minimally invasive esophagectomy with open esophagectomy in 207 patients with esophageal cancer. There was a lower rate of postoperative morbidity in the minimally invasive arm compared with the open esophagectomy arm (35.9% vs 64.4%; P = .0001) and fewer pulmonary complications (17.7% vs 30.1%; P = .037). There was no difference in 30-day mortality (4.9% in each arm of the trial). The findings provide evidence for the short-term benefits of minimally invasive surgery for patients with resectable esophageal cancer.
Bevacizumab + FOLFOXIRI arm doubles 5-year survival compared to Bevacizumab + FOLFIRI in metastatic colorectal cancer trial
6. Adding Bevacizumab to Aggressive Chemo Regimen Doubles 5-Year Colorectal Cancer Survival: Frontline treatment with FOLFOXIRI chemotherapy plus bevacizumab in patients with metastatic colorectal cancer improved survival over FOLFIRI chemotherapy with bevacizumab by 4 months. The median overall survival was 29.8 months in the FOLFOXIRI group compared with 25.8 months in the standard FOLFIRI treatment group (P = .030). Patients in the FOLFOXIRI treatment arm were 20% less likely to die of their disease compared with those in the control arm. The more intensive chemotherapy regimen also doubled the 5-year overall survival rate from 12.4% in the FOLFIRI treatment arm to 24.9% in the FOLFOXIRI treatment arm.
Anti-PD-1 therapy active in gastric cancer
7. Immunotherapy Produces Response in Gastric Cancer: Of the 39 advanced gastric cancer patients treated with the anti-PD-1 monoclonal antibody pembrolizumab, 22.2% had an objective response. The median time to response was 8 weeks. Five patients (13.9%) had stable disease. The median duration of response was 24 weeks and ranged from 8 to more than 33 weeks. The 6-month progression-free survival rate was 24% and the 6-month overall survival rate was 69%. The median follow-up was 8.8 months.
Radiation therapy as effective and less toxic than chemoradiation for palliation of dysphagia
8. Radiation Therapy as Effective as Chemoradiotherapy at Reducing Dysphagia in Esophageal Cancer: Michael Gordon Penniment, MBBS, FRANZCR, MBA, of the Royal Adelaide Hospital, presenting results of a multinational phase III study that compared radiotherapy with chemoradiotherapy for the palliation of dysphagia in patients with advanced esophageal cancer. In patients treated with radiation therapy alone, 41% achieved a maintained improvement in swallowing; in patients treated with chemoradiotherapy, 47% achieved an improvement (P = .4163). Bowel toxicity was worse in patients who received chemoradiotherapy.
Higher Vitamine D Levels correlate with better colorrectal cancer outcomes
9. Higher Vitamin D Levels, Better Colorectal Cancer Outcomes: Newly diagnosed metastatic colorectal cancer patients with higher vitamin D levels had better outcomes after treatment with a combination of chemotherapy and targeted therapy. The difference in median overall survival between the patients in the highest and lowest quintile of vitamin D levels was 8.1 months. The median overall survival was 32.6 months among patients with the highest vitamin D levels compared with 24.5 months for patients with the lowest vitamin D levels (P = .002). Patients with higher concentrations of circulating vitamin D were 20% less likely to have disease progression compared with those with low circulating vitamin D levels (P = .02).
Lanreotide delays disease progression in pancreatic neuroendocrine tumors
10. Lanreotide Delays Disease Progression in PNETs: Alexandria T. Phan, MD, presenting results of the CLARINET study, which found that lanreotide autogel/depot delayed disease progression in patients with metastatic pancreatic neuroendocrine tumors (PNETs). The trial randomized 91 patients to receive either lanreotide (n = 42) or placebo (n = 49). Median progression-free survival was not reached at study end in patients who received lanreotide vs 12.1 months in those who received placebo. The evidence of lanreotide’s antitumor effects along with favorable long-term safety data support the drug’s use as a first-line treatment for PNETs.
Me too, Ramucirumab increases some breaths to a near breathlessness in second-line colorectal cancer...
11. Another Angiogenesis-Targeting Antibody Active in Advanced Colorectal Cancer: The combination of ramucirumab, an antiangiogenesis antibody, and second-line FOLFIRI chemotherapy delayed disease progression and increased survival slightly in patients with metastatic colorectal cancer who had previously progressed on first-line therapy. Patients treated with ramucirumab plus FOLFIRI were 16% less likely to die of their disease compared with those treated with FOLFIRI alone (P = .0219).
References
MM-398 (A Liposomal Irinotecan) + 5-FU/Leucovorin improves survival in patients with pancreatic cancer previously treated with gemcitabine.
1. MM-398 Combo Shows Benefit in Metastatic Pancreatic Cancer: Li-Tzong Chen, MD, PhD, presenting results from the phase III NAPOLI-1 trial, which found that combining MM-398 with 5-FU/leucovorin chemotherapy in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy resulted in improved survival compared with 5-FU/leucovorin alone. The overall survival analysis showed an advantage for patients taking the combination MM-398 plus 5-FU/leucovorin (6.1 months vs 4.2 months; stratified hazard ratio [HR] = 0.57; P = .0009). There was no significant survival advantage for patients assigned MM-398 alone compared with 5-FU/leucovorin alone.
Some patients with stage I-III rectal cancer MAY avoid surgery
2. Low-Risk Group Can Avoid Surgery for Locally Advanced Rectal Cancer: A retrospective analysis of 145 stage I–III rectal cancer patients shows that those patients who have a complete response after chemoradiotherapy and chemotherapy had a similar 4-year survival rate regardless of whether they had surgery or opted for surveillance. In general, about 40% of patients with stage I–III disease have disappearance of their tumors after systemic therapy. The 4-year overall survival rate was 91% and 95% in the no surgery and standard surgery groups, respectively. There was no difference in the rate of distant recurrences between the two groups. “These data continue to suggest that non-operative management does not compromise oncologic outcome, and that preservation of the rectum is achieved in a majority of patients,” concluded the authors.
Second-line Ramucirumab benefit restricted to elevated AFP levels in patients with hepato-cellular carcinoma
3. Baseline AFP Levels Affect Ramucirumab Benefit in HCC: Andrew X. Zhu, MD, PhD, of Massachusetts General Hospital Cancer Center, presenting results from the phase III REACH study, which found that alpha-fetoprotein (AFP) levels could serve as a prognostic indicator in advanced hepatocellular carcinoma (HCC) patients treated with second-line ramucirumab. Treatment with ramucirumab resulted in a significant survival advantage for patients with a baseline AFP level of 400 ng/mL or greater (7.8 months vs 4.2 months; HR = 0.674; P = .0059). The drug did not confer a survival advantage among patients with lower baseline AFP levels (10.1 months vs 11.8 months).
AMG-337, a MET Inhibitor, highly active in patients with MET-amplified gastroesophageal tumors
4. Small Molecule MET Inhibitor Active in Gastroesophageal Cancer: Of the 13 patients with MET-amplified tumors treated once daily with AMG-337, a small molecule MET inhibitor, 8 had a partial or near complete response. AMG-337 is a potent and selective inhibitor that targets both wild-type and some mutant forms of MET. The subset of patients with MET-amplified gastroesophageal junction, gastric, and esophageal cancers responded to treatment. One responder had tumor shrinkage of more than 90%. Based on these phase I results, a phase II trial in MET-amplified gastroesophageal junction, gastric, and esophageal cancers is currently ongoing.
Minimally invasive esophagectomy affords less short-term morbidity in phase III trial
5. Minimally Invasive vs Open Esophagectomy in Esophageal Cancer: Christophe Mariette, MD, PhD, of the department of digestive and oncologic surgery, Claude Huriez University Hospital, presenting data from the phase III MIRO study that compared hybrid minimally invasive esophagectomy with open esophagectomy in 207 patients with esophageal cancer. There was a lower rate of postoperative morbidity in the minimally invasive arm compared with the open esophagectomy arm (35.9% vs 64.4%; P = .0001) and fewer pulmonary complications (17.7% vs 30.1%; P = .037). There was no difference in 30-day mortality (4.9% in each arm of the trial). The findings provide evidence for the short-term benefits of minimally invasive surgery for patients with resectable esophageal cancer.
Bevacizumab + FOLFOXIRI arm doubles 5-year survival compared to Bevacizumab + FOLFIRI in metastatic colorectal cancer trial
6. Adding Bevacizumab to Aggressive Chemo Regimen Doubles 5-Year Colorectal Cancer Survival: Frontline treatment with FOLFOXIRI chemotherapy plus bevacizumab in patients with metastatic colorectal cancer improved survival over FOLFIRI chemotherapy with bevacizumab by 4 months. The median overall survival was 29.8 months in the FOLFOXIRI group compared with 25.8 months in the standard FOLFIRI treatment group (P = .030). Patients in the FOLFOXIRI treatment arm were 20% less likely to die of their disease compared with those in the control arm. The more intensive chemotherapy regimen also doubled the 5-year overall survival rate from 12.4% in the FOLFIRI treatment arm to 24.9% in the FOLFOXIRI treatment arm.
Anti-PD-1 therapy active in gastric cancer
7. Immunotherapy Produces Response in Gastric Cancer: Of the 39 advanced gastric cancer patients treated with the anti-PD-1 monoclonal antibody pembrolizumab, 22.2% had an objective response. The median time to response was 8 weeks. Five patients (13.9%) had stable disease. The median duration of response was 24 weeks and ranged from 8 to more than 33 weeks. The 6-month progression-free survival rate was 24% and the 6-month overall survival rate was 69%. The median follow-up was 8.8 months.
Radiation therapy as effective and less toxic than chemoradiation for palliation of dysphagia
8. Radiation Therapy as Effective as Chemoradiotherapy at Reducing Dysphagia in Esophageal Cancer: Michael Gordon Penniment, MBBS, FRANZCR, MBA, of the Royal Adelaide Hospital, presenting results of a multinational phase III study that compared radiotherapy with chemoradiotherapy for the palliation of dysphagia in patients with advanced esophageal cancer. In patients treated with radiation therapy alone, 41% achieved a maintained improvement in swallowing; in patients treated with chemoradiotherapy, 47% achieved an improvement (P = .4163). Bowel toxicity was worse in patients who received chemoradiotherapy.
Higher Vitamine D Levels correlate with better colorrectal cancer outcomes
9. Higher Vitamin D Levels, Better Colorectal Cancer Outcomes: Newly diagnosed metastatic colorectal cancer patients with higher vitamin D levels had better outcomes after treatment with a combination of chemotherapy and targeted therapy. The difference in median overall survival between the patients in the highest and lowest quintile of vitamin D levels was 8.1 months. The median overall survival was 32.6 months among patients with the highest vitamin D levels compared with 24.5 months for patients with the lowest vitamin D levels (P = .002). Patients with higher concentrations of circulating vitamin D were 20% less likely to have disease progression compared with those with low circulating vitamin D levels (P = .02).
Lanreotide delays disease progression in pancreatic neuroendocrine tumors
10. Lanreotide Delays Disease Progression in PNETs: Alexandria T. Phan, MD, presenting results of the CLARINET study, which found that lanreotide autogel/depot delayed disease progression in patients with metastatic pancreatic neuroendocrine tumors (PNETs). The trial randomized 91 patients to receive either lanreotide (n = 42) or placebo (n = 49). Median progression-free survival was not reached at study end in patients who received lanreotide vs 12.1 months in those who received placebo. The evidence of lanreotide’s antitumor effects along with favorable long-term safety data support the drug’s use as a first-line treatment for PNETs.
Me too, Ramucirumab increases some breaths to a near breathlessness in second-line colorectal cancer...
11. Another Angiogenesis-Targeting Antibody Active in Advanced Colorectal Cancer: The combination of ramucirumab, an antiangiogenesis antibody, and second-line FOLFIRI chemotherapy delayed disease progression and increased survival slightly in patients with metastatic colorectal cancer who had previously progressed on first-line therapy. Patients treated with ramucirumab plus FOLFIRI were 16% less likely to die of their disease compared with those treated with FOLFIRI alone (P = .0219).
References
1. Chen L-T, Von Hoff DD, Li C-P, et al. Expanded analyses of napoli-1: Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 234.
2. Smith JJ, Chow OS, Eaton A, et al. Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 509.
3. Zhu AX, Ryoo B-Y, Yen C-J, et al. Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): Analysis of patients with elevated α-fetoprotein (AFP) from the randomized phase III REACH study. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 232.
4. Kwak EL, LoRusso P, Hamid O, et al. Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 1.
5. Mariette C, Meunier B, Pezet D, et al. Hybrid minimally invasive versus open oesophagectomy for patients with oesophageal cancer: A multicenter, open-label, randomized phase III controlled trial, the MIRO trial. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 5.
6. Cremolini C, Loupakis F, Masi G, et al. FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (mCRC): Updated survival results of the phase III TRIBE trial by the GONO group. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 657.
7. Muro K, Bang Y-J, Shankaran V, et al. Relationship between PD-L1 expression and clinical outcomes in patients (Pts) with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (Pembro; MK-3475) in KEYNOTE-012. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 3.
8. Penniment MG. Full report of the TROG 03.01, NCIC CTG ES2 multinational phase III study in advanced esophageal cancer comparing palliation of dysphagia and quality of life in patients treated with radiotherapy or chemoradiotherapy. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 6.
9. Ng K, Venook AP, Sato K, et al. Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance). 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 507.
10. Phan AT, Caplin ME, Pavel ME, et al. Effects of lanreotide autogel/depot (LAN) in pancreatic neuroendocrine tumors (pNETs): A subgroup analysis from the CLARINET study. 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 233.
11. Tabernero J, Cohn AL, Obermannova R, et al. RAISE: A randomized, double-blind, multicenter phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab (RAM) or placebo (PBO) in patients (pts) with metastatic colorectal carcinoma (CRC) progressive during or following first-line combination therapy with bevacizumab (bev), oxaliplatin (ox), and a fluoropyrimidine (fp). 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 512.
12. Shah MA, Cho JY, Tan IB, et al. Randomized phase II study of FOLFOX +/- MET inhibitor, onartuzumab (O), in advanced gastroesophageal adenocarcinoma (GEC). 2015 ASCO Gastrointestinal Cancers Symposium. Abstract 2.
- See more at: http://www.cancernetwork.com/conference-report/top-highlights-2015-asco-gi-cancers-symposium?GUID=55E68B2A-A7AF-4582-936D-065FF6175374&XGUID=&rememberme=1&ts=24012015#sthash.NBpzx60O.dpuf2015-01-21
Curso de Oncología CES 2015 - 01
Página web del curso
Programa definitivo curso de Oncología CES 2015-01 (28/01/2015)
Descripción de los cambios:
Sustituciones: José Julián Acevedo (no puede asumir las clases porque lo aceptaron en una rotación de oncología en la Mayo Clinic en Rochester). Mateo Mejía se encarga de sus clases. Fernando Herazo se encarga de la clase de cirugía oncológica.
Cambios de horarios: Mauricio Luján (oncología gastrointestinal) cambia de hora con David Gómez (radioterapia). Se consolida el bloque de ginecología oncológica para la mañana del viernes después de radioterapia, y se traslada carcinoma metastásico de primario desconocido a la tarde del jueves, todas a cargo de Milena Roldán.
Introducción y generalidades (Mauricio Lema)
Lunes
2015.02.02.14:00 Bienvenida, Introducción a la oncología (Mauricio Lema)
2015.02.02.15:00 Qué es el cáncer, conceptos básicos (Mauricio Lema)
2015.02.02.16:00 El problema del cáncer, en el Mundo, en Colombia, para el médico (Mauricio Lema)
Ciencias básicas, factores de riesgo, tamizaje, detección precoz y principios terapéuticos en oncología.
Martes
2015.02.03.07:00 Biología del cáncer - 1: Conceptos fundamentales (Mauricio Lema).
2015.02.03.08:30 Biología del cáncer - 2: Vías de señalización críticas en oncología y oncohematología (90 min) (Mauricio Lema)
2015.02.03.14:00 Factores de riesgo en oncología - cómo intervenirlos? (Mateo Mejía)
2015.02.03.15:30 Emergencias oncológicas (90 min) (Mateo Mejía)
Miércoles
2015.02.04.07:00 Tamizaje oncológico (Milena Roldán)
2015.02.04.09:00 Detección precoz del cáncer (Milena Roldán)
2015.02.04.11:00 Principios de tratamiento oncológico 1: Conceptos básicos de cirugía oncológica (90 minutos) (Fernando Herazo) (NUEVO)
2015.02.04.14:00 Cáncer de colon, recto y estómago (120 minutos) (Mauricio Luján)
2015.02.04.16:00 Principios de tratamiento oncológico 2: Conceptos básicos de terapia sistémica (120 minutos) (Mauricio Lema) (NUEVO)
Algunos tumores sólidos seleccionados
Jueves
2015.02.05.06:00 Cáncer de próstata (Mauricio Lema)
2015.02.05.08:00 Cáncer de mama (Rubén Darío Salazar)
2015.02.05.14:00 Cáncer de pulmón (Diego Morán)
2015.02.05.16:00 Carcinoma metastásico de primario desconocido (90 minutos) (Milena Roldán)
Viernes
2015.02.06.07:00 Principios de tratamiento oncológico 3: Conceptos básicos de radioterapia oncológica (90 minutos) (David Gómez)
2015.02.06.08:30 Cáncer de cérvix uterino (Milena Roldán)
2015.02.06.10:30 Carcinoma de ovario (90 minutos) (Milena Roldán)
Bloque de hemato-oncología
2015.02.06.13:30 Enfoque de pacientes con tumores hematológicos (90 min) (Mauricio Lema)
2015.02.06.15:00 Conceptos generales de leucemias agudas y crónicas (90 min) (Mauricio Lema)
2015.02.06.16:30 Conceptos generales de neoplasias linfoides (linfomas y mieloma) (120 min) (Rubén Darío Salazar)
-----------------
Programa preliminar inicial (como fue inicialmente pensado)
Introducción y generalidades (Mauricio Lema)
2015.02.02.14:00 Bienvenida, Introducción a la oncología (Mauricio Lema)
2015.02.02.15:00 Qué es el cáncer, conceptos básicos (Mauricio Lema)
2015.02.02.16:00 El problema del cáncer, en el Mundo, en Colombia, para el médico (Mauricio Lema)
Ciencias básicas, factores de riesgo, tamizaje, detección precoz y principios terapéuticos en oncología.
2015.02.03.07:00 Biología del cáncer - 1: Conceptos fundamentales (Mauricio Lema).
2015.02.03.08:30 Biología del cáncer - 2: Vías de señalización críticas en oncología y oncohematología (90 min) (Mauricio Lema)
2015.02.03.14:00 Factores de riesgo en oncología - cómo intervenirlos? (José Julián Acevedo)
2015.02.03.15:30 Emergencias oncológicas (90 min) (José Julián Acevedo)
2015.02.04.07:00 Tamizaje oncológico (Milena Roldán)
2015.02.04.09:00 Detección precoz del cáncer (Milena Roldán)
2015.02.04.11:00 Principios de tratamiento oncológico 1: Conceptos básicos de cirugía oncológica (90 minutos) (Dr. Díaz) (NUEVO)
2015.02.04.14:00 Principios de tratamiento oncológico 2: Conceptos básicos de radioterapia oncológica (90 minutos) (David Gómez)
2015.02.04.16:00 Principios de tratamiento oncológico 3: Conceptos básicos de terapia sistémica (120 minutos) (Mauricio Lema) (NUEVO)
Algunos tumores sólidos seleccionados
2015.02.05.06:00 Cáncer de próstata (Mauricio Lema)
2015.02.05.08:00 Cáncer de mama (Rubén Darío Salazar)
2015.02.05.14:00 Cáncer de pulmón (Diego Morán)
2015.02.05.16:00 Cáncer de cérvix (Milena Roldán)
2015.02.05.17:00 Cáncer de ovario (Milena Roldán) - EN DISCUSIÓN (Posible toxicidad de información para el estudiante)
2015.02.06.07:00 Cáncer de colon (Mauricio Luján)
2015.02.06.09:00 Cáncer de estómago (60 min) (Mauricio Luján)
2015.02.06.11:00 Carcinoma metastásico de primario desconocido (90 minutos) (Milena Roldán)
Bloque de hemato-oncología
2015.02.06.13:30 Enfoque de pacientes con tumores hematológicos (90 min) (Mauricio Lema)
2015.02.06.15:00 Conceptos generales de leucemias agudas y crónicas (90 min) (Mauricio Lema)
2015.02.06.16:30 Conceptos generales de neoplasias linfoides (linfomas y mieloma) (120 min) (Rubén Darío Salazar)
Programa definitivo curso de Oncología CES 2015-01 (28/01/2015)
Descripción de los cambios:
Sustituciones: José Julián Acevedo (no puede asumir las clases porque lo aceptaron en una rotación de oncología en la Mayo Clinic en Rochester). Mateo Mejía se encarga de sus clases. Fernando Herazo se encarga de la clase de cirugía oncológica.
Cambios de horarios: Mauricio Luján (oncología gastrointestinal) cambia de hora con David Gómez (radioterapia). Se consolida el bloque de ginecología oncológica para la mañana del viernes después de radioterapia, y se traslada carcinoma metastásico de primario desconocido a la tarde del jueves, todas a cargo de Milena Roldán.
Introducción y generalidades (Mauricio Lema)
Lunes
2015.02.02.14:00 Bienvenida, Introducción a la oncología (Mauricio Lema)
2015.02.02.15:00 Qué es el cáncer, conceptos básicos (Mauricio Lema)
2015.02.02.16:00 El problema del cáncer, en el Mundo, en Colombia, para el médico (Mauricio Lema)
Ciencias básicas, factores de riesgo, tamizaje, detección precoz y principios terapéuticos en oncología.
Martes
2015.02.03.07:00 Biología del cáncer - 1: Conceptos fundamentales (Mauricio Lema).
2015.02.03.08:30 Biología del cáncer - 2: Vías de señalización críticas en oncología y oncohematología (90 min) (Mauricio Lema)
2015.02.03.14:00 Factores de riesgo en oncología - cómo intervenirlos? (Mateo Mejía)
2015.02.03.15:30 Emergencias oncológicas (90 min) (Mateo Mejía)
Miércoles
2015.02.04.07:00 Tamizaje oncológico (Milena Roldán)
2015.02.04.09:00 Detección precoz del cáncer (Milena Roldán)
2015.02.04.11:00 Principios de tratamiento oncológico 1: Conceptos básicos de cirugía oncológica (90 minutos) (Fernando Herazo) (NUEVO)
2015.02.04.14:00 Cáncer de colon, recto y estómago (120 minutos) (Mauricio Luján)
2015.02.04.16:00 Principios de tratamiento oncológico 2: Conceptos básicos de terapia sistémica (120 minutos) (Mauricio Lema) (NUEVO)
Algunos tumores sólidos seleccionados
Jueves
2015.02.05.06:00 Cáncer de próstata (Mauricio Lema)
2015.02.05.08:00 Cáncer de mama (Rubén Darío Salazar)
2015.02.05.14:00 Cáncer de pulmón (Diego Morán)
2015.02.05.16:00 Carcinoma metastásico de primario desconocido (90 minutos) (Milena Roldán)
Viernes
2015.02.06.07:00 Principios de tratamiento oncológico 3: Conceptos básicos de radioterapia oncológica (90 minutos) (David Gómez)
2015.02.06.08:30 Cáncer de cérvix uterino (Milena Roldán)
2015.02.06.10:30 Carcinoma de ovario (90 minutos) (Milena Roldán)
Bloque de hemato-oncología
2015.02.06.13:30 Enfoque de pacientes con tumores hematológicos (90 min) (Mauricio Lema)
2015.02.06.15:00 Conceptos generales de leucemias agudas y crónicas (90 min) (Mauricio Lema)
2015.02.06.16:30 Conceptos generales de neoplasias linfoides (linfomas y mieloma) (120 min) (Rubén Darío Salazar)
-----------------
Programa preliminar inicial (como fue inicialmente pensado)
Introducción y generalidades (Mauricio Lema)
2015.02.02.14:00 Bienvenida, Introducción a la oncología (Mauricio Lema)
2015.02.02.15:00 Qué es el cáncer, conceptos básicos (Mauricio Lema)
2015.02.02.16:00 El problema del cáncer, en el Mundo, en Colombia, para el médico (Mauricio Lema)
Ciencias básicas, factores de riesgo, tamizaje, detección precoz y principios terapéuticos en oncología.
2015.02.03.07:00 Biología del cáncer - 1: Conceptos fundamentales (Mauricio Lema).
2015.02.03.08:30 Biología del cáncer - 2: Vías de señalización críticas en oncología y oncohematología (90 min) (Mauricio Lema)
2015.02.03.14:00 Factores de riesgo en oncología - cómo intervenirlos? (José Julián Acevedo)
2015.02.03.15:30 Emergencias oncológicas (90 min) (José Julián Acevedo)
2015.02.04.07:00 Tamizaje oncológico (Milena Roldán)
2015.02.04.09:00 Detección precoz del cáncer (Milena Roldán)
2015.02.04.11:00 Principios de tratamiento oncológico 1: Conceptos básicos de cirugía oncológica (90 minutos) (Dr. Díaz) (NUEVO)
2015.02.04.14:00 Principios de tratamiento oncológico 2: Conceptos básicos de radioterapia oncológica (90 minutos) (David Gómez)
2015.02.04.16:00 Principios de tratamiento oncológico 3: Conceptos básicos de terapia sistémica (120 minutos) (Mauricio Lema) (NUEVO)
Algunos tumores sólidos seleccionados
2015.02.05.06:00 Cáncer de próstata (Mauricio Lema)
2015.02.05.08:00 Cáncer de mama (Rubén Darío Salazar)
2015.02.05.14:00 Cáncer de pulmón (Diego Morán)
2015.02.05.16:00 Cáncer de cérvix (Milena Roldán)
2015.02.05.17:00 Cáncer de ovario (Milena Roldán) - EN DISCUSIÓN (Posible toxicidad de información para el estudiante)
2015.02.06.07:00 Cáncer de colon (Mauricio Luján)
2015.02.06.09:00 Cáncer de estómago (60 min) (Mauricio Luján)
2015.02.06.11:00 Carcinoma metastásico de primario desconocido (90 minutos) (Milena Roldán)
Bloque de hemato-oncología
2015.02.06.13:30 Enfoque de pacientes con tumores hematológicos (90 min) (Mauricio Lema)
2015.02.06.15:00 Conceptos generales de leucemias agudas y crónicas (90 min) (Mauricio Lema)
2015.02.06.16:30 Conceptos generales de neoplasias linfoides (linfomas y mieloma) (120 min) (Rubén Darío Salazar)
2014-12-30
Criterios de respuesta tumoral
Se presentan aquí los criterios de respuesta de valoración respuesta tumoral en oncología basados en los criterios RECIST. También se mencionan los criterios de Lugano (para linfomas) y los criterios de Choi (para tumores estromales gastrointestinales - GISTs). Presentación por la estudiante de medicina de la Universidad CES, Verónica Posada, 28/12/2014.
2014-12-22
2014-12-19
2014-12-15
SABCS 2014 - Adjuvant chemotherapy
NSABP-B36: Adjuvant FEC100 x6 vs AC x4 in Node Negative BC
After 82 months, there is no difference in DFS in both arms. Slightly more toxicity with FEC100. Conclusion: No need for 6 cycles of anthracyclines in node-negative disease.
ECOG 1199: How to give adjuvant taxanes in the adjuvant setting (the four arm trial)
Node-positive or high-risk node-negative BC patients received adjuvant AC and were randomized to one of four arms: paclitaxel every three weeks (control), paclitaxel every week, docetaxel every three weeks and docetaxel every week. Several years ago, it was reported that weekly paclitaxel and docetaxel every three weeks had superior DFS compared to the control arm. After 12 years, the results hold. There appear to be some refinements: 1. Obesity and black ethnicity are associated with decreased OS, 2. Weekly paclitaxel is associated with increased DFS and OS in TNBC with a HR of 0.69 (p<0 .05="" a="" i="" in="">post-hoc
analysis (the 10-year DFS went from 59% to 69% and the OS from 66% to 75%). 3. Docetaxel every three weeks appears slightly superior in DFS (but no OS) with a HR of 0.76 in ER+/HER2-/Unknown patients.
ICE: Adjuvant Ibandronate and Capecitabine in 65+ years High-Risk BC and with High Charlson Co-morbidity score
Negative trial.
After 82 months, there is no difference in DFS in both arms. Slightly more toxicity with FEC100. Conclusion: No need for 6 cycles of anthracyclines in node-negative disease.
ECOG 1199: How to give adjuvant taxanes in the adjuvant setting (the four arm trial)
Node-positive or high-risk node-negative BC patients received adjuvant AC and were randomized to one of four arms: paclitaxel every three weeks (control), paclitaxel every week, docetaxel every three weeks and docetaxel every week. Several years ago, it was reported that weekly paclitaxel and docetaxel every three weeks had superior DFS compared to the control arm. After 12 years, the results hold. There appear to be some refinements: 1. Obesity and black ethnicity are associated with decreased OS, 2. Weekly paclitaxel is associated with increased DFS and OS in TNBC with a HR of 0.69 (p<0 .05="" a="" i="" in="">post-hoc
analysis (the 10-year DFS went from 59% to 69% and the OS from 66% to 75%). 3. Docetaxel every three weeks appears slightly superior in DFS (but no OS) with a HR of 0.76 in ER+/HER2-/Unknown patients.
ICE: Adjuvant Ibandronate and Capecitabine in 65+ years High-Risk BC and with High Charlson Co-morbidity score
Negative trial.
SABCS 2014 - Hormone Receptor Positive (HR+) BC
Predicting response to hormone therapy in neoadjuvant BC
JM Dixon et al. developed a binary assay that includes: a baseline assessment of mRNA expression of IL-6 related gene and the apoptotic neutral nerve growth factor receptor asociated protein; and also includes two proliferation markers on day 14 on Letrozole. This assay predicts with 96% accuracy the likelihood of response to hormone therapy. The investigators undertook sequential biopsies and subjected them to in-depth genomic analysis. They found that responding patients were losing mutations over time, and the contrary was true in non-responding patients. In Dr. Dixon's view, lack of early biologic effect has ominous implications to the natural history for the BC patient.
OPPORTUNE trial: Pictilisib + Anastrozole vs Anastrozole alone prior to surgery in HR+ BC
The addition of Pictilisib (formerly known as GDC-0941), a pan-PI3k inhibitor, to Anastrozole showed a marked decrease in the Ki67 proliferative index, restricted to the Luminal B cohort or patients. No apparent benefit was seen in the Luminal A patients. The FERGI trial was performed in with the same agent in the metastatic setting, and no clear benefit - so far.
Clinical benefit with 1st-Line hormonal therapy for metastastic breast cancer no different in visceral metastasis to non-visceral metastasis
Disease control of patients with visceral metastasis was carefully assessed in three large randomized trials in the 1st-line metastatic setting in hormone-sensitive breast cancer (Tamoxifen vs Exemestane; Tamoxifen vs Anastrozol; and Tamoxifen vs Fulvestrant). The investigators found that the clinical benefit in this visceral metastasis group was 58% (not unlike the 66% in the soft-tissue/bone metastasis group). Dr. John Robertson concludes that it is unlikely that any 1st-line chemotherapy will afford superior disease control. But he CONTRADICTS himself by stating that if the patient has life-threatening disease she should undergo chemotherapy. If hormone is as good as chemo, why not give it to the sickest?
FIRST trial: Fulvestrant 500 mg vs Anastrozole in 1st-line HR+ mBC
Again, Dr. Robertson, presents the results of this small (205 patient) phase-2 trial with the newer 500 mg formulation of Fulvestrant (a estrogen receptor (ER) inactivator) vs Anastrozole (as the control arm). Fulvestrant has three mechanisms of actions: 1. Blocks the dimerization of ER, 2. Begrades ER and 3. Impairs ER-related pathway cross-talk. The original primary endpoint was clinical benefit rate and it was previously reported. The investigators found a slightly superior, albeit non-statistically significant, clinical benefit rate in favor of the Fulvestrant arm (76% vs 67%). Overall survival was included in a protocol amendment in 2011, the results of which are presented for the first time at this meeting. And the results are impressive: 30% improvement in OS to 54 months median overall survival. We are waiting the results of the phase-3 FALCON trial in 2-3 years. Just a couple of decades ago, the median survival of this group of patients was 24 months.
JM Dixon et al. developed a binary assay that includes: a baseline assessment of mRNA expression of IL-6 related gene and the apoptotic neutral nerve growth factor receptor asociated protein; and also includes two proliferation markers on day 14 on Letrozole. This assay predicts with 96% accuracy the likelihood of response to hormone therapy. The investigators undertook sequential biopsies and subjected them to in-depth genomic analysis. They found that responding patients were losing mutations over time, and the contrary was true in non-responding patients. In Dr. Dixon's view, lack of early biologic effect has ominous implications to the natural history for the BC patient.
OPPORTUNE trial: Pictilisib + Anastrozole vs Anastrozole alone prior to surgery in HR+ BC
The addition of Pictilisib (formerly known as GDC-0941), a pan-PI3k inhibitor, to Anastrozole showed a marked decrease in the Ki67 proliferative index, restricted to the Luminal B cohort or patients. No apparent benefit was seen in the Luminal A patients. The FERGI trial was performed in with the same agent in the metastatic setting, and no clear benefit - so far.
Clinical benefit with 1st-Line hormonal therapy for metastastic breast cancer no different in visceral metastasis to non-visceral metastasis
Disease control of patients with visceral metastasis was carefully assessed in three large randomized trials in the 1st-line metastatic setting in hormone-sensitive breast cancer (Tamoxifen vs Exemestane; Tamoxifen vs Anastrozol; and Tamoxifen vs Fulvestrant). The investigators found that the clinical benefit in this visceral metastasis group was 58% (not unlike the 66% in the soft-tissue/bone metastasis group). Dr. John Robertson concludes that it is unlikely that any 1st-line chemotherapy will afford superior disease control. But he CONTRADICTS himself by stating that if the patient has life-threatening disease she should undergo chemotherapy. If hormone is as good as chemo, why not give it to the sickest?
FIRST trial: Fulvestrant 500 mg vs Anastrozole in 1st-line HR+ mBC
Again, Dr. Robertson, presents the results of this small (205 patient) phase-2 trial with the newer 500 mg formulation of Fulvestrant (a estrogen receptor (ER) inactivator) vs Anastrozole (as the control arm). Fulvestrant has three mechanisms of actions: 1. Blocks the dimerization of ER, 2. Begrades ER and 3. Impairs ER-related pathway cross-talk. The original primary endpoint was clinical benefit rate and it was previously reported. The investigators found a slightly superior, albeit non-statistically significant, clinical benefit rate in favor of the Fulvestrant arm (76% vs 67%). Overall survival was included in a protocol amendment in 2011, the results of which are presented for the first time at this meeting. And the results are impressive: 30% improvement in OS to 54 months median overall survival. We are waiting the results of the phase-3 FALCON trial in 2-3 years. Just a couple of decades ago, the median survival of this group of patients was 24 months.
SABCS 2014 - Triple negative breast cancer (TNBC)
Biomarkers
Myriad-genetics has sponsored two trials on biomarkers in TNBC. The first one in metastatic TNBC comparing Carboplatin to Docetaxel in TNBC (TNT trial). The study showed no difference between Carboplatin and Docetaxel. But, in when the germ-line BRCA+ mTNBC patients were analyzed, the results became quite interesting. The response rate in BRCA+ mTNBC was 68% vs 33% in favor of Carboplatin. The non-basal TNBC (by PAM50) had a remarkable response to Docetaxel (but, it was a small subgroup of patients). The company has also created a genetic test called HRD (Homologous Recombination Deficiency) test to assess the integrity of the DNA repair mechanism in TNBC patients. In a companion trial, patients with early breast cancer had a 52% response rate to platinum if they tested positive to HRD, and only 10% if the results were negative.
Geparsepto: Nab-Paclitaxel in neoadjuvant BC
The germans presented they large Geparsepto trial with about 1200 patients comparing neoadjuvant Paclitaxel followed by EC to nab-Paclitaxel (150 mg/wk) followed by EC. The endpoint was pathologic complete response (pCR). Nab-paclitaxel arm exhibited higher neuropathy and diarrhea. The study met its primary endpoint with an increase in the pCR from 28% to 39% (p=0.001). The results were impressive in the TNBC group with pCR of 48% (25% with the conventional paclitaxel).
Pembrolizumab in TNBC
A phase 1b trial reported by Rita Nanda with Pembrolizumab 10 mg/kg IV q2wk in 32 heavily pretreated PD-L1+ (by IHC) TNBC patients. There were 5 responses in the 27 evaluable patients (ORR: 18.5%), with 1 CR. The median duration of response was >40 weeks (in responding patients), and 1.9 mo (in the others). Treatment was well tolerated, one patient with rapidly progressive metastatic disease died of disseminated intravascular coagulation.
Myriad-genetics has sponsored two trials on biomarkers in TNBC. The first one in metastatic TNBC comparing Carboplatin to Docetaxel in TNBC (TNT trial). The study showed no difference between Carboplatin and Docetaxel. But, in when the germ-line BRCA+ mTNBC patients were analyzed, the results became quite interesting. The response rate in BRCA+ mTNBC was 68% vs 33% in favor of Carboplatin. The non-basal TNBC (by PAM50) had a remarkable response to Docetaxel (but, it was a small subgroup of patients). The company has also created a genetic test called HRD (Homologous Recombination Deficiency) test to assess the integrity of the DNA repair mechanism in TNBC patients. In a companion trial, patients with early breast cancer had a 52% response rate to platinum if they tested positive to HRD, and only 10% if the results were negative.
Geparsepto: Nab-Paclitaxel in neoadjuvant BC
The germans presented they large Geparsepto trial with about 1200 patients comparing neoadjuvant Paclitaxel followed by EC to nab-Paclitaxel (150 mg/wk) followed by EC. The endpoint was pathologic complete response (pCR). Nab-paclitaxel arm exhibited higher neuropathy and diarrhea. The study met its primary endpoint with an increase in the pCR from 28% to 39% (p=0.001). The results were impressive in the TNBC group with pCR of 48% (25% with the conventional paclitaxel).
Pembrolizumab in TNBC
A phase 1b trial reported by Rita Nanda with Pembrolizumab 10 mg/kg IV q2wk in 32 heavily pretreated PD-L1+ (by IHC) TNBC patients. There were 5 responses in the 27 evaluable patients (ORR: 18.5%), with 1 CR. The median duration of response was >40 weeks (in responding patients), and 1.9 mo (in the others). Treatment was well tolerated, one patient with rapidly progressive metastatic disease died of disseminated intravascular coagulation.
2014-12-10
2014-12-09
2014-12-08
ASH 2014 - Lymphoma & Multiple Myeloma
Hodgkin's Lymphoma
Upfront therapy
1. Brentuximab Vedotin instead of Bleomycin in ABVD (both share pulmonary toxicity): 96% 3-yr failure-free survival in advanced-stage Hodgkin's Lymphoma. Phase III studies are under way.
Relapsed / Refractory disease
1. Brentuximab + Bendamustine in preparation to autologous stem-cell transplantation: Small study, outpatient, ORR in the 90% range, and CR in the 80% range.
2. AETHERA trial shows higher 2-yr PFS in patients receiving consolidation with Brentuximab after Stem-Cell Transplantation for Hodgkin's Lymphoma (65% vs 45%), poised to become a new standard-of-care.
3. Nivolumab (anti PD-1 monoclonal antibody) in post-transplant relapse: Hodgkin's lymphoma is an ideal model for immune checkpoint modulation due to high immunocyte infiltration around the tumor cells. There is a Phase 1 study with up to 80% response rate in heavily pretreated patients (including patients previously treated with Brentuximab Vedotin). This is the most exciting result in lymphoma in this ASH 2014 (NEJM On-line first).
Low-grade lymphomas
1. Ibrutinib in follicular lymphoma: Ibrutinib showed only 30% response rate in relapse follicular lymphoma patients (somewhat disappointing). Whereas Idelalisib (PI3k inhibitor) shows 50% response rate with a median PFS of up to a year in chemo & rituximab refractory follicular lymphoma patients (and is FDA approved in that indication).
2. EFS12 as a prognostic marker in follicular lymphoma: A Mayo clinic dataset has shown that patients who have not had an event at 12 months after either initial treatment or observation have a life expectancy similar to age-matched controls. The converse is true, patients that have events within a year will not do well, and require a more aggressive approach.
Diffuse Large B-cell lymphoma (DLBCL)
1. Double-hit DLBCL: Abnormalities in both c-Myc and bcl-2 genes should be looked in high Ki67/proliferative DLCL. Some studies show that DA-EPOCH is effective with PFS in the 60% at 1-year.
2. Selenexor (a nuclear trafficking inhibitor): some 40% response rate in relapsed DLBCL, with some CRs, in phase-I trials.
Mantle-Cell lymphoma (MCL)
1. Intensive therapy is still disappointing in MCL: The current theme in MCL is highly aggressive upfront chemotherapy (R-CHOP alternating with DHAP, followed by transplant; R-CHOP followed by Bortezomib; Bortezomib + Rituximab + Bendamustine). All these trials are showing some relapses at the 3-year mark.
2. Chemo-free for MCL with Lenalidomide + Rituximab in 1-st line: Small study (38 patients) with median age of 65: 88% went into remission and 2-yr EFS in 80%.
Multiple Myeloma
Upfront therapy
1. Carfilzomib in 1st-line multiple myeloma patients: An italian trial showed very high response rate in the order of >75% in patients receiving high-dose weekly Carfilzomib + Cyclophosphamide + Dexamethasone.
2. Ixazomib, an oral proteasome inhibitor, + Lenalidomide + Dexamethasone: The all oral combination chemotherapy was well tolerated and exhibited high response rate.
Relapsed / Refractory disease
1. ASPIRE trial (Carfilzomib + Lenalidomide + Dexamethasone): Possibly the most outstanding result of the ASH 2014 (NEJM On-line first). Carfilzomib + Lenalidomide + Dexamethasone increases the PFS by 9 months over Lenalidomide + Dexamethasona in relapsed multiple myeloma patiens (26 months vs 17 months). The benefit was also seen in patients with high-risk cytogenetics. Quality-of-life was also superior in the Carfilzomib-based arm.
2. Oral proteasome inhibitors: Several presentations showed that both Ixazomib and Oprozomib are active in heavily-treated myeloma patients. Specifically, Oprozomib showed a single-agent activity with 30% response-rate in Carfilzomib-refractory patients. A change in formulation to tablet, and the use of antiemetic agents decreased its chemotherapy-induced nausea and vomiting. Still, not ready for prime time.
3. Anti CD38 monoclonal antibodies (MoAbs): CD38 is a surface marker in plasmocytes (and other blood cells). Daratumumab and SAR650984 are MoAbs that have shown activity in myeloma patients. In this ASH it was presented a combination of Daratumumab + Lenalidomide + Dexamethasone in relapsed myeloma patients. No added toxicity was found beyond a few infusion reactions.
4. Histone Deacetylase (HDAC) inhibitors (Panobinostat): Some interesting results with Panobinostat in relapsed/refractory myeloma. Further studies are required, especially to deal with its gastrointestinal toxicity.
5. Ibrutinib: The Bruton Tyrosine Kinase inhibitor, Ibrutinib has exhibited high clinical benefit rate of 50% with a median PFS of 6 months in heavily pre-treated myeloma patients. Another interesting agent that merits further investigation in this condition.
Maintenance
The longer exposure to anti-myeloma agents, the better. Post transplant lenalidomide maintenance is highly effective with responses that occur over several months. Some other trials have shown that Bortezomib maintenance is also highly effective.
Pomalidomide
1. Single-agent pomalidomide in heavily pre-treated myeloma: The newer imid Pomalidomide has shown to be effective as a single-agent, with a response rate of about 35%.
2. Pomalidomide in combination with other agents: In this ASH there are reports that show that Pomalidomide can be safely combined with Bortezomib + Dexamethasone, with Cyclophosphamide + Dexamethasone, also with Liposomal Doxorubicine + Dexamethasone with very good safety profile, and response rate in the range of 60-70%.
3. Safety of Pomalidomide in renal insufficiency: Some data were presented that show that Pomalidomide can be safely administered in pretty much any patient with any degree of renal dysfunction, provided they are not in dialysis.
Upfront therapy
1. Brentuximab Vedotin instead of Bleomycin in ABVD (both share pulmonary toxicity): 96% 3-yr failure-free survival in advanced-stage Hodgkin's Lymphoma. Phase III studies are under way.
Relapsed / Refractory disease
1. Brentuximab + Bendamustine in preparation to autologous stem-cell transplantation: Small study, outpatient, ORR in the 90% range, and CR in the 80% range.
2. AETHERA trial shows higher 2-yr PFS in patients receiving consolidation with Brentuximab after Stem-Cell Transplantation for Hodgkin's Lymphoma (65% vs 45%), poised to become a new standard-of-care.
3. Nivolumab (anti PD-1 monoclonal antibody) in post-transplant relapse: Hodgkin's lymphoma is an ideal model for immune checkpoint modulation due to high immunocyte infiltration around the tumor cells. There is a Phase 1 study with up to 80% response rate in heavily pretreated patients (including patients previously treated with Brentuximab Vedotin). This is the most exciting result in lymphoma in this ASH 2014 (NEJM On-line first).
Low-grade lymphomas
1. Ibrutinib in follicular lymphoma: Ibrutinib showed only 30% response rate in relapse follicular lymphoma patients (somewhat disappointing). Whereas Idelalisib (PI3k inhibitor) shows 50% response rate with a median PFS of up to a year in chemo & rituximab refractory follicular lymphoma patients (and is FDA approved in that indication).
2. EFS12 as a prognostic marker in follicular lymphoma: A Mayo clinic dataset has shown that patients who have not had an event at 12 months after either initial treatment or observation have a life expectancy similar to age-matched controls. The converse is true, patients that have events within a year will not do well, and require a more aggressive approach.
Diffuse Large B-cell lymphoma (DLBCL)
1. Double-hit DLBCL: Abnormalities in both c-Myc and bcl-2 genes should be looked in high Ki67/proliferative DLCL. Some studies show that DA-EPOCH is effective with PFS in the 60% at 1-year.
2. Selenexor (a nuclear trafficking inhibitor): some 40% response rate in relapsed DLBCL, with some CRs, in phase-I trials.
Mantle-Cell lymphoma (MCL)
1. Intensive therapy is still disappointing in MCL: The current theme in MCL is highly aggressive upfront chemotherapy (R-CHOP alternating with DHAP, followed by transplant; R-CHOP followed by Bortezomib; Bortezomib + Rituximab + Bendamustine). All these trials are showing some relapses at the 3-year mark.
2. Chemo-free for MCL with Lenalidomide + Rituximab in 1-st line: Small study (38 patients) with median age of 65: 88% went into remission and 2-yr EFS in 80%.
Multiple Myeloma
Upfront therapy
1. Carfilzomib in 1st-line multiple myeloma patients: An italian trial showed very high response rate in the order of >75% in patients receiving high-dose weekly Carfilzomib + Cyclophosphamide + Dexamethasone.
2. Ixazomib, an oral proteasome inhibitor, + Lenalidomide + Dexamethasone: The all oral combination chemotherapy was well tolerated and exhibited high response rate.
Relapsed / Refractory disease
1. ASPIRE trial (Carfilzomib + Lenalidomide + Dexamethasone): Possibly the most outstanding result of the ASH 2014 (NEJM On-line first). Carfilzomib + Lenalidomide + Dexamethasone increases the PFS by 9 months over Lenalidomide + Dexamethasona in relapsed multiple myeloma patiens (26 months vs 17 months). The benefit was also seen in patients with high-risk cytogenetics. Quality-of-life was also superior in the Carfilzomib-based arm.
2. Oral proteasome inhibitors: Several presentations showed that both Ixazomib and Oprozomib are active in heavily-treated myeloma patients. Specifically, Oprozomib showed a single-agent activity with 30% response-rate in Carfilzomib-refractory patients. A change in formulation to tablet, and the use of antiemetic agents decreased its chemotherapy-induced nausea and vomiting. Still, not ready for prime time.
3. Anti CD38 monoclonal antibodies (MoAbs): CD38 is a surface marker in plasmocytes (and other blood cells). Daratumumab and SAR650984 are MoAbs that have shown activity in myeloma patients. In this ASH it was presented a combination of Daratumumab + Lenalidomide + Dexamethasone in relapsed myeloma patients. No added toxicity was found beyond a few infusion reactions.
4. Histone Deacetylase (HDAC) inhibitors (Panobinostat): Some interesting results with Panobinostat in relapsed/refractory myeloma. Further studies are required, especially to deal with its gastrointestinal toxicity.
5. Ibrutinib: The Bruton Tyrosine Kinase inhibitor, Ibrutinib has exhibited high clinical benefit rate of 50% with a median PFS of 6 months in heavily pre-treated myeloma patients. Another interesting agent that merits further investigation in this condition.
Maintenance
The longer exposure to anti-myeloma agents, the better. Post transplant lenalidomide maintenance is highly effective with responses that occur over several months. Some other trials have shown that Bortezomib maintenance is also highly effective.
Pomalidomide
1. Single-agent pomalidomide in heavily pre-treated myeloma: The newer imid Pomalidomide has shown to be effective as a single-agent, with a response rate of about 35%.
2. Pomalidomide in combination with other agents: In this ASH there are reports that show that Pomalidomide can be safely combined with Bortezomib + Dexamethasone, with Cyclophosphamide + Dexamethasone, also with Liposomal Doxorubicine + Dexamethasone with very good safety profile, and response rate in the range of 60-70%.
3. Safety of Pomalidomide in renal insufficiency: Some data were presented that show that Pomalidomide can be safely administered in pretty much any patient with any degree of renal dysfunction, provided they are not in dialysis.
ASH 2014 - Myeloproliferative neoplasms, Myelodysplasia, Acute lymphocytic leukemia and Acute Myeloid Leukemia
Myelofibrosis
1. From the mutational perspective there are three driver mutations in myelofibrosis: JAK2, MPL and CALR. Nevertheless, there are about 10% of patients that are triple-negative, with worse prognosis. All three mutations activate the JAK2 pathway and respond to JAK2 inhibitors. But, some patients deemed Low-Risk by clinical criteria can move up to High-Risk based on the mutational pattern, therefore transplantations should be offered sooner to them. Several additional passenger mutations have been discovered that reflect clonal evolution and deal mainly with epigenetic phenomena.
2. Currently, there are three new research avenues in myelofibrosis: 1. Addition of another agent to the JAK2 inhibitor: JAK2 inhibitors are good at decreasing inflammation and spleen, but they are not good at improving blood counts. There are studies combining JAK2 inhibitors with PI3k inhibitors, Hedgehog inhibitors, HiDAC inhibitors, Antifibrotic agents. 2. Exploring selective JAK1 inhibitor: it appears that JAK1 inhibitor may provide anti-inflammatory effects, but it is less effective on the splenomegaly. 3. A promising anti-Telomerase agent is under study with some patients achieving complete remission. Will have to see the actual results in this meeting.
Polycythemia vera (PV)
Just 3 days ago, Ruxolitinib was approved by the FDA for 2nd-line therapy in PV in patients resistant or intolerant to Hydrea. (The presenter summarizes what the standard of care of PV is: you treat with phlebotomy, aspirin and probably Hydrea the majority of PV patiens. The goal is to keep the hematocrit below 45% in order to decrease the risk of thrombosis. The actual indication for Hydrea is patient older than 60 or a history of thrombosis). About 25% of patients do not tolerate Hydrea, and they don't do well. Ruxolitinib becomes an option for these patients (it is estimated that about 25.000 patients are going to need it in the US alone). In this ASH there will be a presentation on QoL with Ruxoilitinib, showing a marked improvement in several aspects with Ruxolitinib.
Essential thrombocythemia (ET)
1. ET is the most benign of the myeloproliferative neoplasms, with nearly normal life-expectancy. It can be treated with aspirin, Hydrea or Anagrelide. Ruxolitinib is not as good in ET compared to its results in Myelofibrosis and PV. It affords adequate response in 70-80% High-Risk ET patients; but may cause significant anemia.
2. Pegylated-Interferon (Pegassys) has shown activity in both PV and ET, and appears quite effective in both. In this ASH there is going to be a presentation on the impact of the mutation status and response to pegylated interferon in MPN.
Myelodysplasia (MDS)
1. MDS - Negative results of S117 (Azacytidine vs Azacytidine + Vorinostat vs Azacytidine + Lenalidomide)
Enrolled about 280 patients, no difference in response in the three arms, combination therapy more toxic, more patients came out of the study due to toxicity, some evidence of longer PFS with combination, not powered to detect OS benefit. Does not change practice.
2. Rigosertib not effective in 2nd-Line MDS after hypomethylating agents in a Phase 3 trial
OS increased from 5 to about 8 months, not reaching statistical significance. An oral formulation is still being developed with some encouraging results, but it is not ready for prime-time.
3. New treatment options for Low-Risk (LR) MDS
LR-MDS patients are treated with EPO or Lenalidomide (indicated in del-5q MDS, buy often used "off-label" in other settings). But some patients are refractory to these agents (or have high EPO blood levels predicting a poor response to a pharmacologic EPO formulation).
There are two promising agents in this particular setting, and both share the same mechanism of action as ligand traps to the TGF-Beta receptor superfamily (Sotatercept: an activin type IIA receptor-fusion protein, and ACE-536: a modified activin type IIB receptor-fusion protein). It is known that TGF-Beta mediates anemia and chronic inflammation. Some preliminary results show up to 40% response rate (including transfusion-independence) to Sotatercept, and further results are going to be presented at this ASH with both agents. It is interesting to know that these agents are bone-morphogenetic factors that show promise in osteoporosis, multiple myeloma, thalassemia, and Castleman disease.
Newer agents in Acute Lymphoblastic Leukemia (ALL)
The FDA approved Blinatumumab (CD19-CD3 bi-specific antibody) for refractory and relapsed B-Cell ALL. There are other agents under investigation: a CD-19 conjugated to a toxin, Inotuzumab (CD22 conjugated to ozogamycin), CAR-T-Cells. Inotuzumab also appears very promising and it is now on a Phase III trial.
Acute Myeloid Leukemia (AML)
1. Sorafenib + Anthracycline + Cytarabine in AML: Not quite there.
In the SORAML trial Sorafenib was added to standard induction chemotherapy in AML and was found to increase event-free survival (3-yr EFS 56% vs 38%, with PFS of 21 vs 9 months, in favor of the Sorafenib arm) and relapse-free survival was also superior in the Sorafenib. But no OS advantage was detected (but the study was underpowered to detect it, with only 276 patients). The speaker points out that Sorafenib is used off-label in relapsed FLT3 mutated patients (sometimes in combination with hypomethylating agents) with very good results. Interestingly, the response to sorafenib in the german trial was not restricted to FLT3 mutation+ AML.
2. DH2 inhibitors are promising in IDH2 mutated AML
Isocytrate dehydrogenase-2 (IDH2) is mutated in about 20% of AML. Anti IDH2 agents are clearly EFFECTIVE in this group of patients achieving significant cytoreduction allowing some highly refractory patients to bridge to allo-transplantation.
1. From the mutational perspective there are three driver mutations in myelofibrosis: JAK2, MPL and CALR. Nevertheless, there are about 10% of patients that are triple-negative, with worse prognosis. All three mutations activate the JAK2 pathway and respond to JAK2 inhibitors. But, some patients deemed Low-Risk by clinical criteria can move up to High-Risk based on the mutational pattern, therefore transplantations should be offered sooner to them. Several additional passenger mutations have been discovered that reflect clonal evolution and deal mainly with epigenetic phenomena.
2. Currently, there are three new research avenues in myelofibrosis: 1. Addition of another agent to the JAK2 inhibitor: JAK2 inhibitors are good at decreasing inflammation and spleen, but they are not good at improving blood counts. There are studies combining JAK2 inhibitors with PI3k inhibitors, Hedgehog inhibitors, HiDAC inhibitors, Antifibrotic agents. 2. Exploring selective JAK1 inhibitor: it appears that JAK1 inhibitor may provide anti-inflammatory effects, but it is less effective on the splenomegaly. 3. A promising anti-Telomerase agent is under study with some patients achieving complete remission. Will have to see the actual results in this meeting.
Polycythemia vera (PV)
Just 3 days ago, Ruxolitinib was approved by the FDA for 2nd-line therapy in PV in patients resistant or intolerant to Hydrea. (The presenter summarizes what the standard of care of PV is: you treat with phlebotomy, aspirin and probably Hydrea the majority of PV patiens. The goal is to keep the hematocrit below 45% in order to decrease the risk of thrombosis. The actual indication for Hydrea is patient older than 60 or a history of thrombosis). About 25% of patients do not tolerate Hydrea, and they don't do well. Ruxolitinib becomes an option for these patients (it is estimated that about 25.000 patients are going to need it in the US alone). In this ASH there will be a presentation on QoL with Ruxoilitinib, showing a marked improvement in several aspects with Ruxolitinib.
Essential thrombocythemia (ET)
1. ET is the most benign of the myeloproliferative neoplasms, with nearly normal life-expectancy. It can be treated with aspirin, Hydrea or Anagrelide. Ruxolitinib is not as good in ET compared to its results in Myelofibrosis and PV. It affords adequate response in 70-80% High-Risk ET patients; but may cause significant anemia.
2. Pegylated-Interferon (Pegassys) has shown activity in both PV and ET, and appears quite effective in both. In this ASH there is going to be a presentation on the impact of the mutation status and response to pegylated interferon in MPN.
Myelodysplasia (MDS)
1. MDS - Negative results of S117 (Azacytidine vs Azacytidine + Vorinostat vs Azacytidine + Lenalidomide)
Enrolled about 280 patients, no difference in response in the three arms, combination therapy more toxic, more patients came out of the study due to toxicity, some evidence of longer PFS with combination, not powered to detect OS benefit. Does not change practice.
2. Rigosertib not effective in 2nd-Line MDS after hypomethylating agents in a Phase 3 trial
OS increased from 5 to about 8 months, not reaching statistical significance. An oral formulation is still being developed with some encouraging results, but it is not ready for prime-time.
3. New treatment options for Low-Risk (LR) MDS
LR-MDS patients are treated with EPO or Lenalidomide (indicated in del-5q MDS, buy often used "off-label" in other settings). But some patients are refractory to these agents (or have high EPO blood levels predicting a poor response to a pharmacologic EPO formulation).
There are two promising agents in this particular setting, and both share the same mechanism of action as ligand traps to the TGF-Beta receptor superfamily (Sotatercept: an activin type IIA receptor-fusion protein, and ACE-536: a modified activin type IIB receptor-fusion protein). It is known that TGF-Beta mediates anemia and chronic inflammation. Some preliminary results show up to 40% response rate (including transfusion-independence) to Sotatercept, and further results are going to be presented at this ASH with both agents. It is interesting to know that these agents are bone-morphogenetic factors that show promise in osteoporosis, multiple myeloma, thalassemia, and Castleman disease.
Newer agents in Acute Lymphoblastic Leukemia (ALL)
The FDA approved Blinatumumab (CD19-CD3 bi-specific antibody) for refractory and relapsed B-Cell ALL. There are other agents under investigation: a CD-19 conjugated to a toxin, Inotuzumab (CD22 conjugated to ozogamycin), CAR-T-Cells. Inotuzumab also appears very promising and it is now on a Phase III trial.
Acute Myeloid Leukemia (AML)
1. Sorafenib + Anthracycline + Cytarabine in AML: Not quite there.
In the SORAML trial Sorafenib was added to standard induction chemotherapy in AML and was found to increase event-free survival (3-yr EFS 56% vs 38%, with PFS of 21 vs 9 months, in favor of the Sorafenib arm) and relapse-free survival was also superior in the Sorafenib. But no OS advantage was detected (but the study was underpowered to detect it, with only 276 patients). The speaker points out that Sorafenib is used off-label in relapsed FLT3 mutated patients (sometimes in combination with hypomethylating agents) with very good results. Interestingly, the response to sorafenib in the german trial was not restricted to FLT3 mutation+ AML.
2. DH2 inhibitors are promising in IDH2 mutated AML
Isocytrate dehydrogenase-2 (IDH2) is mutated in about 20% of AML. Anti IDH2 agents are clearly EFFECTIVE in this group of patients achieving significant cytoreduction allowing some highly refractory patients to bridge to allo-transplantation.
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