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Immunotherapy, BRAF inhibitor sequence affected outcomes in metastatic melanoma
Prior treatment with immunotherapy did not limit response to BRAF inhibitors among patients with metastatic melanoma, according to results of a retrospective study.
However, patients who underwent initial treatment with BRAF inhibitors and subsequently received immunotherapy with ipilimumab (Yervoy, Bristol-Myers Squibb) demonstrated poorer outcomes, results showed.
Patients with BRAF-positive metastatic melanoma have several treatment options, including BRAF inhibitors vemurafenib (Zelboraf, Hoffmann-La Roche) and dabrafenib (Taflinar, GlaxoSmithKline), the MEK inhibitor trametinib (Mekinist, GlaxoSmithKline), and the immunotherapy agents ipilimumab and interleukin-2. Yet, there are limited data with regard to optimal sequencing, according to researchers.
The analysis included 32 patients who had received immunotherapy before a BRAF inhibitor, and 242 patients who received the BRAF inhibitor first.
The overall response rate was higher among patients who received a BRAF inhibitor prior to immunotherapy (66% vs. 57%). Patients treated with immunotherapy first demonstrated longer median PFS (6.7 months vs. 5.6 months) and median OS (19.6 months vs. 13.4 months).
Response rates, PFS and OS were similar between groups after researchers controlled for prognostic variables.
Of the patients who received a BRAF inhibitor first, 193 discontinued treatment. OS was 2.9 months (range, 1.8-4.4) from the day of discontinuation.
Forty patients who underwent BRAF inhibitor treatment first went on to receive ipilimumab. Only half of these patients completed four doses of immunotherapy, according to researchers. Among ipilimumab-treated patients, PFS was 2.7 months (95% CI, 1.8-3.1) and OS was 5 months (95% CI, 3-8.8).
“In this retrospective analysis, prior treatment with immunotherapy does not appear to negatively influence response to BRAF inhibitors,” the researchers wrote. “Outcomes for immunotherapy with ipilimumab following BRAF inhibitor discontinuation are poor. Randomized controlled trials are needed to define if sequencing immunotherapy prior to BRAF inhibitor therapy is superior to sequencing BRAF inhibitor prior to immunotherapy.”
Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.