Wednesday, July 22, 2015

Nivo/Opdivo effective no matter BRAF!!!!

Efficacy and safety of Nivolumab in patients with BRAF V600 Mutant and BRAF Wild-type advanced melanoma:  A pooled analysis of 4 clincal trials.  Larkin, Lao, Urba, Wolchok et al.  JAMA Oncol.  2015 July 1.

The anti-PD1 antibody, nivolumab, has demonstrated clinical activity in patients with advanced melanoma.  The activity of nivo in subgroups of patients with tumors which have wild-type BRAF kinase vs patients with tumors having mutant BRAF has not systematically been explored in a large dataset.  This is an analysis of data pooled from 4 clinical trials of nivo in 440 patents with unresectable stage III of stage IV melanoma who had been tested for BRAF mutational status.  Nivo was given IV at doses of 0.1, 0.3, 1.0, 3.0 or 10.0 mg/kg every 2 weeks until disease progression, discontinuation due to adverse effects, withdrawal, or end of study.  Most patients (83%) were given 3 mg/kg.

Of the 440 patients from 4 clinical trials, 334 were BRAF wild-type and 106 were positive for the BRAF V600 mutation.  In patients evaluable for response, the objective response rates were 34.6% for the 217 patients with wild-type BRAF status and 29.7% for the 74 with mutant BRAF status.  The objective response rates did not seem to be affected by prior BRAF inhibitor therapy, prior ipi therapy, or PD-L1 status of the tumor.  The median duration of objective response was 14.8 months for wild-type BRAF and 11.2 months for mutant BRAF.  Median time to objective response was 2.2 months in both patients groups.  Incidence of adverse events were 68% in the wild-type BRAF group and 58% in the mutant BRAF group.  

The results of this retrospective analysis suggest that nivo has similar efficacy and safety outcomes in patients with wild-type or mutant BRAF, regardless of prior BRAFi or ipi treatment.

1.  Suspect that my trial ratties were reviewed given the dosages.
2.  A little surprised that there were so few mutant BRAF patients as the breakdown is about 50/50 BRAF positive vs BRAF wild-type in melanoma patients.  Wonder if trial requirements played a role.
3.  Still getting conflicting info of whether prior ipi and PD-L1 status affect response rates.  Hope that will clear up soon.
4.  Good info for lots of patients!!!  This was reported at ASCO 2014:  Nivo/opdivo effectiveness in melanoma

Hang in there my friends! - c

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