Five-Year OS Nears 40% in BRAF Wild Type Melanoma

Five-Year OS Nears 40% in BRAF Wild Type Melanoma

Almost 40% of patients with advanced BRAF wild type melanoma remained alive at 5 years after treatment with the PD-1 inhibitor nivolumab (Opdivo), follow-up data from a randomized trial showed.

By comparison, fewer than half as many patients randomized to dacarbazine were alive at 5 years. Almost 10 times as many patients treated with nivolumab were alive without disease progression as compared with the dacarbazine group.

Among the 20% of patients who had complete responses (CRs) with nivolumab, 88% were alive at 5 years, Caroline Robert, MD, PhD, of Gustave Roussy Institute in Villejuif, France, and coauthors reported in the Journal of Clinical Oncology.

“The results here show that the probability of being alive at five years depends on the type of response achieved,” the authors wrote. “Those with CR do better than those with PR [partial response] long term, the former making up a near majority of patients alive at five years (47%).”

“The five-year results of CheckMate 066 presented here add to the growing body of evidence supporting long-term survival with PD-1 inhibitors. Such long-term survival seems associated with achieving a durable response to treatment and can be maintained after treatment discontinuation (even without subsequent systemic therapies) and without new long-term safety concerns.”

The first author of a recent analysis of long-term data for 1,500 patients treated with a competing PD-1 inhibitor, pembrolizumab (Keytruda), agreed with nivolumab investigators’ assessment of anti-PD-1 effectiveness in advanced/metastatic melanoma.

“The five-year follow-up of the CheckMate 066 trial by Robert et al confirms the unprecedented benefit from PD-1 inhibitors in patients with metastatic melanoma, regardless of BRAF status,” Igor Puzanov, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, told MedPage Today by email.

“Moreover, the benefits are durable even for the portion of patients who ultimately stop regular dosing, seemingly related to the depth of response,” he continued. “Questions remain on the best approach for patients who do not have complete or near-complete responses and predictors of response. The quest for cure continues for those patients.”

Puzanov and coauthors reported an objective response rate of 35-40% in patients with either BRAF-mutant or wild type melanoma. Progression-free survival (PFS) was about 20% at 4 years, and OS was 35-40%, irrespective of BRAF status.

The CheckMate 066 results also were consistent with several other studies. CheckMate 067 showed 5-year OS and PFS of 43% and 32% in patients with BRAF wild type melanoma treated with nivolumab. The individual trials included in the pooled analysis reported by Puzanov and colleagues yielded similar response and survival data in BRAF wild type melanoma.

CheckMate 066 included 418 patients with untreated, unresectable stage III/IV, BRAF wild type melanoma. They were randomized to standard doses of nivolumab or dacarbazine, and the primary endpoint was OS.

After a minimum follow-up of 60 months from the last randomized patient, the nivolumab arm had a median OS of 37.3 months as compared with 11.2 months for the dacarbazine arm. The 5-year OS was 39% with nivolumab and 17% with dacarbazine, a difference that represented a 50% reduction in the hazard ratio (95% CI 0.40-0.63, P<0.0001). Also at 5 years, the difference in survival time between the two treatment groups averaged 14.3 months (34.8 vs 20.5).

Median PFS was 5.1 months with nivolumab versus 2.2 months with dacarbazine. The 5-year PFS was 28% versus 3%, a 60% reduction in the hazard for disease progression or survival (95% CI 0.33-0.54, P<0.0001). Nivolumab led to superior OS and PFS regardless of PD-L1 expression (<5% vs ≥5%) and in patients with normal or elevated levels of lactate dehydrogenase.

Nivolumab led to an objective response rate (ORR) of 42% versus 14% with dacarbazine. Median duration of response was not reached (lower confidence interval 47.2 months) versus 6 months with dacarbazine. Almost a third of responding patients in the nivolumab arm had response duration of 60 months or longer.

Among patients alive at 5 years, the ORR was 81% in the nivolumab arm and 39% in the dacarbazine arm. In a subgroup of patients who were alive at 5 years and did not receive subsequent therapy, the ORR was 92% with nivolumab (48 of 52 patients), including CR in 56%. In the dacarbazine arm, two patients — both of whom had a CR — were alive at 5 years without subsequent therapy.

  • Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow

Disclosures

The CheckMate 066 trial was supported by Bristol Myers Squibb.

Robert disclosed relationships with Bristol Myers Squibb, Roche, Amgen, Novartis, Pierre Fabre, MSD, Sanofi, Biothera, CureVac, and Merck.

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