The biggest news in melanoma treatment from the 2015 American Society of Clinical Oncology (ASCO) annual meeting was undoubtedly the report from a large, phase III, randomized clinical trial that compared a combination of two ‘checkpoint inhibitor’ drugs—nivolumab (Opdivo) and ipilimumab (Yervoy)—with the same drugs given alone.
In the CheckMate-067 trial, 945 previously untreated patients with unresectable stage III or IV melanoma were assigned to Opdivo alone, Opdivo plus Yervoy, or Yervoy alone.
The median progression-free survival (PFS, or the time that passed after treatment without cancer worsening) was 11.5 months with Opdivo plus Yervoy, compared to 2.9 months with Yervoy alone, and 6.9 months with Opdivo alone. In patients whose tumors tested positive for a protein called PD-L1, PFS was even longer in the combination group (14 months). However, in patients with PD-L1-negative tumors, PFS was also longer in the combination group than in the Opdivo-alone group (11.2 vs 5.3 months). This clearly indicates that combination treatment produces superior results, regardless of PD-L1 test results. Unfortunately, this improvement comes with a high rate of adverse effects (side effects)—55.0% in the combination group versus 16.3% in the Opdivo-alone group.
Yervoy is currently a standard-of-care, first-line treatment in metastatic melanoma with normal BRAF. These new results may prompt a change in standard treatment recommendations, based on the findings that even Opdivo given alone, and more so the combination treatment, trump Yervoy. The results reported at ASCO were published almost simultaneously in The New England Journal of Medicine.
The superior activity of the Opdivo plus Yervoy combination treatment was also reported in another presentation at ASCO, in which it was compared to Yervoy alone in melanoma patients with normal BRAF. The competing ‘PD-1 inhibitor’ pembrolizumab (Keytruda) was featured in a presentation that reported a response rate of 34%, and 1- and 2-year overall survival rates of 66% and 49%, respectively. Keytruda is not being tested together with Yervoy for an obvious reason: both Opdivo and Yervoy are drugs made by the company Bristol-Myers Squibb, while Keytruda is made by Merck. Trials of Keytruda combined with radiotherapy or the intralesional drug T-VEC are ongoing, but no results are available yet.