Immune checkpoint inhibitors in adjuvant setting after radical resection of melanoma: a meta-analysis of the pivotal trials

ABSTRACT

Beyond the overall relapse-free survival (RFS) advantage demonstrated in randomized trials (RCT) of adjuvant anti-PD-1 immunotherapy in radically resected stage III–IV melanoma, key issues about subgroups of interest have been raised in recent years, with non-conclusive results when considering single studies. In the present meta analysis, we pooled all RCT data in this setting, analyzing, overall, 3043 patients. The RFS benefit of adjuvant immunotherapy over the comparator (placebo or anti-CTLA-4) was strongly confirmed in the pooled analysis, and it was statistically significant in most subgroups, excluding patients with stage IIIA and stage IV M1c melanoma. Nevertheless, the relative benefit was not statistically significantly different when considering their IIIB-IIIC and M1a-M1b counterparts. Future trials in this setting should consider subgroups of interest for tailoring the adjuvant strategy in terms of duration and drug combination in light of literature data.

KEYWORDS:

• Melanoma
• immune checkpoint inhibitors
• anti-PD-1
• immunotherapy
• adjuvant
• perioperative
• ICI
• nivolumab
• pembrolizumab
• ipilimumab

Disclosure of potential conflicts of interest

Melissa Bersanelli received research funding from Seqirus UK, Pfizer, Novartis, BMS, Astra Zeneca, Roche S.p.A., and Sanofi Genzyme; honoraria as speaker at scientific events by Bristol-Myers Squibb (BMS), Novartis, Astra Zeneca, and Pfizer and as consultant for advisory role by Novartis, BMS, and Pfizer; she also received fees for copyright transfer by Sciclone Pharmaceuticals.

Sebastiano Buti received honoraria as speaker at scientific events and advisory role by Bristol-Myers Squibb (BMS), Pfizer; MSD, Ipsen, Roche, Eli-Lilly, AstraZeneca and Novartis; he also received research funding from Novartis.

Ignazio Stanganelli received honoraria as speaker at scientific meetings by BMS, Novartis, MSD.

The other authors have no conflict of interest to declare.