medwireNews: People with completely resected Merkel cell carcinoma might benefit from adjuvant treatment with nivolumab, indicate phase 2 trial results.
Adjuvant nivolumab was associated with both an absolute and relative reduction in the risk for recurrence or death compared with observation, but the between-group differences did not reach statistical significance.
The study authors attribute this to a better than expected “spontaneous course of the disease in the study cohort (in which only 27% of patients in the observation group showed progression over 2 years of follow-up).”
And therefore, they caution that “the results reported in this interim analysis remain preliminary.”
The researchers believe that the findings of this “prospective randomized controlled—but still exploratory—study provide a promising signal of efficacy to continue ongoing randomised trials in this area […]; however, the statistical assumptions for the case number calculations in these trials should be critically reconsidered.”
They continue: “ADMEC-O suggests that adjuvant immunotherapy is clinically feasible in this area of unmet medical need.”
As reported in The Lancet, the primary endpoint of disease-free survival (DFS) at 1 year and 2 years was 85% and 84%, respectively, among the 118 participants who were randomly assigned to receive nivolumab 480 mg every 4 weeks for up to a year after undergoing complete resection.
The corresponding rates among their 61 counterparts who instead underwent observation were 77% and 73%, which equated to an absolute risk reduction at 1 year of 9% and at 2 years of 10%.
The relative risk reductions with nivolumab versus observation at the two timepoints were 39% and 38%, respectively.
Overall survival among nivolumab-treated patients was an identical 94% at the 1- and 2-year mark, while among those who underwent observation the rates were 96% and 92%, respectively. But Dirk Schadendorf, from University Hospital Essen in Germany, and co-researchers point out that the data “are not mature enough to draw conclusions.”
Turning to the safety profile, they say: “The observed patterns and frequencies of treatment-related adverse events are in line with the good tolerability and known side-effect profile of PD-1 inhibitors; no new safety signals emerged from our trial and no treatment-related deaths occurred.”
Adverse events of grade 3 or 4 were experienced by 42% of participants in the nivolumab arm, with 20% considered related to treatment, and 11% of those in the observation arm.
A total of 22% of nivolumab-treated patients discontinued the PD-1 inhibitor due to adverse events but the treatment-related rate was 15% and only 5% occurred at grade 3 or 4.
The authors of a related commentary, Philippe Saiag and Astrid Blom, both from Université Paris-Saclay in France, “warmly congratulate the authors for conducting a trial in such a rare cancer and in the adjuvant setting.”
But they add that “multiple issues should be addressed before using this strategy routinely.”
The commentators stress the need to “wait for the maturation of the trial, with longer follow-ups, and for the results of other ongoing trials in this population investigating adjuvant avelumab or pembrolizumab.”
Saiag and Blom also highlight that ADMEC-O “is not a typical superiority trial, but an exploratory phase 2 trial in an area without any reference for efficacy, which included a relatively low number of patients, thus lacking statistical power, and in which the hazard ratios reported originate from a post-hoc analysis.”
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Lancet 2023; doi:10.1016/S0140-6736(23)00769-9
Lancet 2023; doi:10.1016/S0140-6736(23)01041-3
