Artigo Acesso aberto Revisado por pares

Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma

2021; Nature Portfolio; Volume: 27; Issue: 2 Linguagem: Inglês

10.1038/s41591-020-01211-7

ISSN

1546-170X

Autores

Elisa A. Rozeman, Esmée P. Hoefsmit, Irene L. M. Reijers, Robyn P.M. Saw, Judith M. Versluis, Oscar Krijgsman, Petros Dimitriadis, Karolina Sikorska, Bart A. van de Wiel, Hanna Eriksson, Maria Gonzalez, A. Torres Acosta, Lindsay G. Grijpink-Ongering, Kerwin F. Shannon, John B.A.G. Haanen, Jonathan R. Stretch, Sydney Ch’ng, Omgo E. Nieweg, Henk Mallo, S. Adriaansz, Ron Kerkhoven, Sten Cornelissen, Annegien Broeks, W. Martin C. Klop, Charlotte L. Zuur, Winan J. van Houdt, Daniel S. Peeper, Andrew J. Spillane, Alexander C.J. van Akkooi, Richard A. Scolyer, Ton N. Schumacher, Alexander M. Menzies, Georgina V. Long, Christian U. Blank,

Tópico(s)

Cancer Immunotherapy and Biomarkers

Resumo

Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN ( NCT02437279 ) and phase 2 OpACIN-neo ( NCT02977052 ) studies1,2. While the results are promising, data on the durability of these pathologic responses and baseline biomarkers for response and survival were lacking. After a median follow-up of 4 years, none of the patients with a pathologic response (n = 7/9 patients) in the OpACIN study had relapsed. In OpACIN-neo (n = 86), the 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (P < 0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-γ score) were associated with pathologic response and low risk of relapse; pRR was 100% in patients with high IFN-γ score/high TMB; patients with high IFN-γ score/low TMB or low IFN-γ score/high TMB had pRRs of 91% and 88%; while patients with low IFN-γ score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-γ score. Our findings provide a strong rationale for a randomized phase 3 study comparing neoadjuvant ipilimumab plus nivolumab versus standard adjuvant therapy with antibodies against the programmed cell death protein-1 (anti-PD-1) in macroscopic stage III melanoma. Long-term outcomes and biomarker analyses of two neoadjuvant immunotherapy clinical trials in melanoma patients support the clinical benefit of this treatment approach and uncover prognostic correlates of response.

Referência(s)