Survival in adult patients with BRAFV600 mutation-positive advanced melanoma: a noninterventional ambispective study of patients with cobimetinib combined with vemurafenib during the French early access program: MELANIS study.

Cobimetinib combined with vemurafenib was available in France in 2015 through a 'Temporary Authorization for Use' program (TAU, preapproval access pending its marketing on 2016) for patients with v-raf murine sarcoma viral oncogene homolog B1-mutant advanced melanoma. This study aimed to provide real-world outcomes in patients previously registered in this TAU. This noninterventional, ambispective, multicentre French study, conducted in patients previously registered in TAU, aimed to estimate overall survival (OS) and progression-free survival (PFS) and to describe the tolerability of the therapeutic combination. At first cobimetinib intake (in combination with vemurafenib), 88% of the 185 evaluable patients had disease stage IV (brain metastasis: 70% of them), 31% had elevated lactate dehydrogenases, and 10% had an Eastern Cooperative Oncology Group (ECOG) index ≥2. Median OS was 16.1 months (95% CI, 12.5-20.7). Brain metastasis ( P < 0.001), ECOG index ≥2 ( P = 0.007), and hepatic impairment ( P = 0.037) were found as independent factors significantly associated with shorter survival. Median PFS was 7.3 months (95% CI, 5.2-8.4). ECOG index ≥2 ( P = 0.006) was significantly associated with shorter PFS. Between cobimetinib start and inclusion, increased CPK (3% of patients), retinal serous detachment (3%), decreased left ventricular ejection fraction (3%), increased transaminases (3%), and rash (3%) were the most reported serious adverse events. This study provides real-world outcomes in France for the vemurafenib-cobimetinib combination available in patients with BRAF-mutant-advanced melanoma. Our data tend to confirm in the real-life setting that this combination therapy is effective in such patients, with a safety profile consistent with previous interventional studies.

Efficacy and Safety of Bevacizumab Combined With First-Line Chemotherapy in Elderly (≥75 Years) Patients With Metastatic Colorectal Cancer: A Real-World Study.

BACKGROUND: Although elderly patients are the first concerned by colorectal cancer (CRC), they are underrepresented in clinical trials. The real-world CASSIOPEE study was thus conducted in elderly patients treated for metastatic CRC (mCRC). METHODS: This French prospective, multicenter, noninterventional study aimed to estimate 1-year progression-free survival (PFS) and overall survival (OS), and describe treatments, patient autonomy (Instrumental Activities of Daily Living; Balducci scale), and safety over 24 months, in patients older than 75 with mCRC, starting first-line bevacizumab plus chemotherapy (NCT01555762). RESULTS: From 2012 to 2014, 402 patients were included (safety population: n = 383, efficacy population: n = 358). Patient characteristics were as follows: mean age, 81 ± 4 years (<80 years, 46%; 80-85 years, 44%; >85 years, 10%); men, 52%; colon primary tumor, 80%; main metastatic site, liver 66%; Eastern Cooperative Oncology Group performance 0-1, 81%. Median PFS was 9.1 months (95% confidence interval [CI]: 8.3-10.2). It was superior for patients ≤85 years (<80 years: 9.3 months; 80-85 years: 9.5 months) compared with patients >85 years (8.3 months). Median OS was 19.0 months (95% CI, 16.5-21.5) and decreased in the 2 oldest groups (20.6, 17.8, and 13.0 months). Autonomy assessments decreased over time leading to nonconclusive results. Twenty-six percent of patients experienced serious adverse events (SAEs): 7% bevacizumab-related SAEs, and 6% bevacizumab-targeted SAEs. Two fatal bevacizumab-related adverse events were reported (hemorrhagic stroke and intestinal ischemia). CONCLUSIONS: This large French real-world study showed that medically fit older patients with mCRC could have a benefit/risk balance similar to that of younger patients when treated with first-line bevacizumab plus chemotherapy. Improvements in geriatric assessments are needed to better define this population.