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Clinical Trial
. 2021 Feb;27(2):256-263.
doi: 10.1038/s41591-020-01211-7. Epub 2021 Feb 8.

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

E A Rozeman  1 , E P Hoefsmit #  2 , I L M Reijers #  1 , R P M Saw  3   4   5 , J M Versluis  1 , O Krijgsman  2   6 , P Dimitriadis  2 , K Sikorska  7 , B A van de Wiel  8 , H Eriksson  9   10 , M Gonzalez  3 , A Torres Acosta  7 , L G Grijpink-Ongering  7 , K Shannon  3   5 , J B A G Haanen  1   2 , J Stretch  3   4   5 , S Ch'ng  3   4   5 , O E Nieweg  3   4   5 , H A Mallo  1 , S Adriaansz  1 , R M Kerkhoven  11 , S Cornelissen  12 , A Broeks  12 , W M C Klop  13 , C L Zuur  13 , W J van Houdt  13 , D S Peeper  2   6 , A J Spillane  3   4   14 , A C J van Akkooi  13 , R A Scolyer  3   15 , T N M Schumacher  2   6 , A M Menzies  3   16 , G V Long  3   16 , C U Blank  17   18
Affiliations
Clinical Trial

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

E A Rozeman et al. Nat Med. 2021 Feb.

Abstract

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.

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References

    1. Blank, C. U. et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nat. Med. 24, 1655–1661 (2018). - DOI
    1. Rozeman, E. A. et al. Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial. Lancet Oncol. 20, 948–960 (2019). - DOI
    1. Hauschild, A. et al. Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAFV600-mutant stage III melanoma. J. Clin. Oncol. https://doi.org/10.1200/JCO.18.01219 (2018).
    1. Eggermont, A. M. M. et al. Longer follow-up confirms recurrence-free survival benefit of adjuvant pembrolizumab in high-risk stage III Melanoma: updated results from the EORTC 1325-MG/KEYNOTE-054 Trial. J. Clin. Oncol. https://doi.org/10.1200/jco.20.02110 (2020).
    1. Ascierto, P. A. et al. Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. https://doi.org/10.1016/s1470-2045(20)30494-0 (2020).

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