Revisiones, conceptos, análisis de casos, staffs médicos y otros documentos relacionados con hematología benigna, hematología maligna y oncología clínica.


ASCO 2015 - CheckMate 067: Improved PFS with Nivolumab (N) + Ipilimumab (I) vs N vs I in metastatic melanoma (in 2 slides)

ASCO 2015
The results of the CheckMate 067 trial were presented. In this trial patients with metastatic melanoma enrolled in the Nivolumab + Ipilimumab arm displayed superior PFS compared to Nivolumab and to Ipilimumab arms. The greatest benefit was observed in the low-PD-L1 expression (publication in the NEJM)


ASCO 2015 - COMBI-d: Improved OS with Dabrafenib + Trametinib vs Dabrafenib + Placebo in mutated BRAF in Metastatic Melanoma (in 3 slides)

COMBI-d: Study design
COMBI-d: Improved OS with Dabrafenib + Trametinib vs Dabrafenib + Placebo
Selected side effects of anti BRAF and anti MEK agents

ASCO 2015
Dr. Long presented the results of the COMBI-d trial with an mOS benefit of 25.1 mo vs 18.7m (HR: 0.71), favoring the combination of Dabrafenib + Trametinib vs Dabrafenib + Placebo. The combination of an anti BRAF + anti MEK is highly superior to single-agent anti BRAF. These results are reinforced by the presentation, at the same meeting, of the coBRIM trial with improved PFS with another anti BRAF + antiMEK combination in the same group of patients (see blog entry).

ASCO 2015 - Update on coBRIM: 1st-line Cobimetinib + Vemurafenib in mutated BRAF metastatic cutaneous melanoma (in 3 slides)

coBRIM: Study design

coBRIM updated PFS at the ASCO 2015 in Chicago

The majority of significant toxicity occurs during the first few weeks of therapy

1. Single-agent Vemurafenib (V) (an oral anti BRAF agent) improves survival in mutated BRAF metastatic melanoma (mMel), based on the BRIM3 trial.
2. Disease control with single-agent anti BRAF is transient.
3. Paradoxical activation of the MAPK pathway appears to be an important mechanism of resistance.
4. MEK (a downstream to BRAC MAPK element) is activated.
5. Single-agent Trimetinib (an oral anti MEK agent) improves PFS in BRAF mutated mMel.
6. coBRIM is a phase III trial comparing V to Cobimetinib (co) (an oral anti MEK agent) + V as 1st-line therapy for mBRAF mMel patients. Initial results have been published in the NEJM in 2014. The study was positive meeting the primary endpoint (see image 1).
7. The toxicity profile of the combination was slightly different to the single-agent V with less proliferative skin neoplasms, slightly more chorioretinitis, CPK and diarrhea. Co-V exhibited similar (high) rate of skin toxicity.
8. Most of the toxicity occurs the first few weeks, and resolves thereafter (see image 3).

ASCO 2015
Dr. Larkin uptdated the results of the coBRIM with a definitive PFS of 12.5 vs 7.2 months (HR: 0.58), favoring the combination of Cobimetinib + Vemurafenib vs Vemurafenib. To date, this is the first study with PFS longer than 1 year in mMel. The combination of an anti BRAF + anti MEK is highly superior to single-agent anti BRAF.

Brief editorial
At the same ASCO, the positive OS results of the COMBI-D trial were presented (see blog entry). In the COMBI-D a different anti BRAF + anti MEK combination were compared to single-agent anti BRAF. Both COMBI-D and coBRIM reinforce the same concept: dual BRAF and MEK pathway blockage appears to be more effective in mBRAF mMel patients. Other relevant trials in the field presented at ASCO 2015 include those with anti PD1 + Ipilimumab (published at the NEJM) This trial was also a positive trial with excellent results. Considering these options (when available to us in Colombia), how should we choose the optimal first line therapy for mBRAF mMel patients: targeted (anti BRAF + anti MEK agents) or immunotherapy (ie, Anti PD1 + Anti CTLA4 agents)? There is no clear-cut answer. Both strategies are very effective, so I will give a tentative answer based on a few considerations.

1. Response rate with targeted agents is extremely high, in the 70% range. Even the most active immunotherapy has less than 50% response rate.
2. Although very active, duration of disease control with targeted agents is finite. Most patients eventually progress. Whereas 1 out of 5 immunotherapy treated patients display a very long disease control akin to cure.
3. Targeted agents are highly effective in CNS metastasis. Immunotherapy is not.
4. A minority of the patients experience disease pseudoprogression with immunotherapy.
5. Both strategies are highly toxic, and are riddled with unusual side-effects, difficult to spot and treat.

So, first-line targeted therapy is my choice for patients with mBRAF mMel with high disease burden, poor PS, CNS disease, or in a patient that can not afford to experience pseudoprogression (or progression). Most mBRAF patients are in this group, since these tumors tend to be fast growing.

For those patients with low-disease burden that can withstand progression or pseudoprogression, I consider first-line immunotherapy as it can provide long-term disease control in a subgroup of patients. Moreover, targeted therapy can be administered for many of  those who do progress.


Curso de Oncología para estudiantes de medicina CES 2015 - 02

Día 1
2015.07.13.6:00 Bienvenida, Introducción a la oncología (Mauricio Lema) 
2015.07.13.7:00 Qué es el cáncer, conceptos básicos (Mauricio Lema) 
2015.07.13.8:00 El problema del cáncer, en el Mundo, en Colombia, para el médico (Mauricio Lema) 
2015.07.13.9:00 Factores de riesgo en oncología - cómo intervenirlos? (Mateo Mejía) 
2015.07.13.10:00 Emergencias oncológicas (90 min) (Mateo Mejía)

Día 2

2015.07.14.06:00 Biología del cáncer - 1: Conceptos fundamentales (90 min) (Mauricio Lema). 
2015.07.14.07:30 Biología del cáncer - 2: Vías de señalización críticas en oncología y oncohematología (90 min) (Mauricio Lema) 
2015.07.14.09:00 Tamizaje oncológico (90 min) (Milena Roldán)
2015.07.14.10:30 Detección precoz del cáncer (90 min) (Milena Roldán)

2015.07.14.13:00 Principios de tratamiento oncológico 1: Conceptos básicos de cirugía oncológica (90 min) (Fernando Herazo) 
2015.07.14.14:30 Cáncer de mama (120 min) (Rubén Darío Salazar) 

Día 3

2015.07.15.06:00 Principios de tratamiento oncológico 2: Conceptos básicos de terapia sistémica (150 min) (Mauricio Lema) 
2015.07.15.08:30 Cáncer de próstata (120 min) (Mauricio Lema) 
2015.07.15.10:30 Cáncer ginecológico: Cáncer de cérvix uterino y Carcinoma de ovario (120 minutos) (Milena Roldán) 

Día 4

2015.07.16.06:00 Cáncer de colon, recto y estómago (120 minutos) (Mauricio Luján)
2015.07.16.08:00 Cáncer de pulmón, enfoque del nódulo pulmonar solitario (120 min) (Diego Morán) 

2015.07.16.10:00 Carcinoma metastásico de primario desconocido (90 minutos) (Milena Roldán) 

Día 5

2015.07.17.06:00 Enfoque de pacientes con tumores hematológicos (90 min) (Mauricio Lema)
2015.07.17.07:30 Conceptos generales de leucemias agudas y crónicas (120 min) (Mauricio Lema)
2015.07.17.14:00 Principios de tratamiento oncológico 3: Conceptos básicos de radioterapia oncológica (90 minutos) (David Gómez)

Día 6

2015.07.21.06:00 Espacio para clase extra, en caso de necesidad
2015.07.21.08:00 Conceptos generales de neoplasias linfoides (linfomas y mieloma) (150 min) (Rubén Darío Salazar)

Tiempo: 30:30 min

Archivo de documentos

Search Engine