Key Melanoma Trials at ASCO Yield Encouraging Survival Data

Jeffrey S. Weber, MD, PhD


June 22, 2018

Hello. I am Dr Jeffrey Weber, deputy director of the Perlmutter Cancer Center at New York University Langone Health in New York City and co-director of its melanoma research program. Welcome to Medscape Oncology Insights.

Today I will briefly discuss some of the emerging data on melanoma treatment that was presented at the 2018 meeting of the American Society of Clinical Oncology (ASCO). We have heard about a number of interesting new trials and seen follow-ups of old trials.

CheckMate 238

The CheckMate 238 adjuvant trial[1] was a large randomized, blinded trial with an active control arm. Patients with resected stage IIIB/C or IV melanoma were randomly allocated to receive either adjuvant nivolumab or adjuvant ipilimumab for 1 year. This was a large trial that included 906 patients and an even 1:1 randomization. With now more than 24 months of follow-up, the updated data suggest that for the primary endpoint of recurrence-free survival, there continues to be a clear benefit for nivolumab compared with ipilimumab. The rate of relapse-free survival at 24 months is 63% for patients on nivolumab versus 50% for those on ipilimumab, a clear benefit. The toxicity profile, of course, has not changed, because those data—which I presented 8 months ago at the European Society for Medical Oncology (ESMO) meeting in Madrid [2]—only went out to 100 days from finishing treatment.

In terms of breaking it down by subgroups, whether PD-L1 positive or negative, BRAF mutated, stage III or stage IV, all of the benefit continues to be maintained with very healthy hazard ratios and very good P values.

Again, the major message is that as the follow-up gets longer, both the recurrence-free survival and the distant metastases–free survival continue to be superior over time for nivolumab compared with the ipilimumab active control. We do not have mature survival data; however, no patients in the nivolumab arm have died, whereas five patients in the ipilimumab arm have died, suggesting that with more time we may begin to see a survival advantage. Again, those data are immature and we will see how that plays out.


The follow-up on the KEYNOTE-006 trial[3] (pembrolizumab vs ipilimumab) includes some very nice data looking at the more than 100 patients (19% of the total) who completed 2 years of treatment on schedule. Currently we have about 2 years of follow-up after finishing treatment in that population, and it suggests that 82%-86% of those patients will actually stay in remission 2 years from finishing 2 years of treatment [with pembrolizumab]—that is, 4 years from initiation of therapy. No median duration of response has been reached in the pembrolizumab group. These are quite impressive data.

Of eight patients who relapsed among the group that finished 2 years of treatment successfully, either in complete remission, partial remission, or even stable, two of those eight went back into remission [after a second course of treatment], including one partial and one complete response; five were stable and only one subsequently progressed. These are small numbers, but they suggest that perhaps you could re-treat patients who finished 2 years [of pembrolizumab], go off, and then relapse at some point in the future—that it may be possible to re-treat those patients with the same drug and achieve some benefit. We will be hearing more about that trial as the data mature.


Finally, we heard about survival data for the first time from the COLUMBUS trial,[4] the three-arm trial of encorafenib plus binimetinib, the BRAF/MEK drugs, versus encorafenib alone or vemurafenib alone as the control arms. These are very interesting data, suggesting a median survival in the combination treatment arm of 33 or more months, which is almost unprecedented in a large BRAF/MEK trial.

The COLUMBUS trial included a total of 577, and 192 patients received the combination of encorafenib and binimetinib; nonetheless, you can't argue with a 33.6-month median survival, a 14.9-month median progression-free survival, and an excellent response rate, which matches what we see with other BRAF/MEK combinations.

[In terms of toxicity,] about 15% of patients suffered retinal detachment.[5] I would question whether this was clinically significant. Was it reversible? Did it need to be treated? The toxicity profiles of all the BRAF/MEK drugs vary, so it's "pick your poison" when choosing among the regimens. But if that survival advantage and progression-free survival advantage hold up, that would be unprecedented in the targeted-therapy field in melanoma.

Thank you for joining me. This is Dr Jeffrey Weber for Medscape.


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