Abstract 807P
Background
Although anti-programmed cell death receptor-1 (PD-1) monotherapy is a standard adjuvant treatment for melanoma patients underwent definitive surgery, their efficacy is evaluated mostly in Caucasians and cutaneous melanoma, it remains unclear in other ethnic groups and melanoma subtypes.
Methods
Clinical data for patients (pts) with resected stage II/III/IV melanoma treated with anti-PD-1 monotherapy both in and outside clinical trial settings between 2015 and 2021 was collected retrospectively from 6 independent institutions in the US, Australia, Japan and China. Survival outcomes (both recurrence free survival [RFS] and overall survival [OS]) were compared by ethnicity (Caucasian versus East-Asian/African) and by different melanoma subtypes (non-acral-cutaneous[NAC]/unknown primary[UP], acral and mucosal).
Results
In total 537 pts were included. Caucasians had significantly longer RFS and OS. Among different melanoma subtypes, NAC/UP had the best RFS and OS, followed by acral. Mucosal melanoma had the poorest survival outcomes. In NAC/UP subtypes, Caucasians had longer RFS (with significance) and OS (with marginal significance) than East Asian/African. In the multivariate analysis incorporating ethnicity, melanoma subtype, age, sex, stage, LDH, and BRAF mutation status, Caucasian ethnicity was independently correlated with significantly better RFS (HR 0.59; 95%CI 0.41-0.84; P=.004) and a trend towards better OS (HR 0.59, 95%CI 0.34-1.02; P=.06), while mucosal subtype independently associated with both poorer RFS (HR 2.43; 95%CI 1.55-3.80; P<.001) and OS (HR 2.97; 95%CI, 1.53-5.78; P=.001). Table: 807P
| Entire Cohort | NAC/UP subtypes | ||||||
| Ethnicity | Mel Subtype | Ethnicity | |||||
| Caucasian | East-Asian /African | NAC/UP | Acral | Mucosal | Caucasian | East-Asian /African | |
| (n=262) | (n=275) | (n=352) | (n=83) | (n=102) | (n=246) | (n=106) | |
| RFS | |||||||
| 1-y rate (%, 95% CI) | 80 (76-86) | 67 (62-73) | 77 (73-82) | 79 (70-88) | 58 (49-69) | 81 (76-86) | 68 (60-78) |
| 2-y rate (%, 95% CI) | 70 (64-76) | 49 (44-56) | 66 (61-71) | 57 (46-70) | 40 (32-52) | 71 (65-77) | 53 (44-64) |
| P value | <.001 | <.001 | <.001 | ||||
| OS | |||||||
| 2-y rate (%, 95% CI) | 92 (88-95) | 80 (75-86) | 90 (87-94) | 83 (74-92) | 75 (67-85) | 92 (89-96) | 85 (78-93) |
| 4-y rate (%, 95% CI) | 83 (78-89) | 55 (46-66) | 82 (77-87) | 57 (38-86) | 46 (36-60) | 84 (78-90) | 78 (69-88) |
| P value | <.001 | <.001 | .07 |
Conclusions
Ethnicity and melanoma subtype both contribute to survival discrepancies in melanoma patients undergoing adjuvant anti-PD-1 monotherapy. The somatic genetic and immunologic underpinning of these differences remain unclear and warrants further investigation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Natural Science Foundation of China, Beijing Municipal Natural Science Foundation.
Disclosure
L. Si: Financial Interests, Personal, Invited Speaker: MSD, Roche, Novartis, Shanghai Junshi Biosciences, Oriengene. K. Flaherty: Financial Interests, Personal, Leadership Role: Clovis Oncology, Strata Oncology, Kinnate, Checkmate Pharmaceuticals, and Scorpion Therapeutics; Financial Interests, Personal, Advisory Role: PIC Therapeutics, Apricity, Tvardi, ALX Oncology, xCures, Monopteros, Vibliome, and Soley Therapeutics; consultant to Takeda, Novartis and Transcode Therapeutics. Y. Nakamura: Financial Interests, Personal, Invited Speaker: Bristol Myers-Squibb, Ono Pharmaceutical, Novartis Pharma, Merck Sharp & Dohme, Maruho, Kyowa Kirin, Tanabe Mitsubishi Pharma, Novartis Pharma; Financial Interests, Personal, Advisory Board: Novartis Pharma; Financial Interests, Institutional, Funding: Ono Pharmaceutical, Kaken Pharma, Torii, POLA Pharma. K. Namikawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Novartis Pharma, MSD, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Novartis Pharma, MSD; Financial Interests, Institutional, Invited Speaker: Ono Pharmaceutical. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Merck Sharpe & Dohme (Australia) Pty Limited, Novartis Pharma AG, OncoSec Medical Australia, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Board, Consultant Advisor: Highlight Therapeutics S.L. A.M. Menzies: Financial Interests, Personal, Advisory Board, advisory board: BMS, MSD, Novartis, Roche, Pierre-Fabre, QBiotics. D.B. Johnson: Financial Interests, Personal, Advisory Board: Array Biopharma, BMS, Incyte, Merck, Novartis; Financial Interests, Personal and Institutional, Research Grant: BMS and Incyte; Financial Interests, Personal, Other, Travel grant: Genentech. R.J. Sullivan: Financial Interests, Personal, Advisory Board: Merck, Novartis, Bristol Myers Squibb, Eisai, Iovance, Oncosec, Pfizer, Replimune; Financial Interests, Personal, Royalties: Up-to-date; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Invited Speaker: GlaxoSmithKline, Pfizer, Sanofi, Moderna, Roche-Genentech, BiomedValley DIscoveries, Astex, Compugen, BeiGene, Novartis, Rubius, Alkermes, Simcha Therapeutics, OnKure. G. Boland: Financial Interests, Personal and Institutional, Research Grant: Takeda Oncology, Palleon Pharmaceuticals, InterVenn Biosciences, and Olink Proteomics; Financial Interests, Personal, Advisory Role: Merck, InterVenn Biosciences, and Ankyra Therapeutics; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Nektar Therapeutics. J. Guo: Financial Interests, Personal, Advisory Board: MSD, Roche, Bayer, Novartis, Simcere Pharmaceutical Group, Shanghai Junshi Biosciences, Oriengene; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Leadership Role: CSCO. All other authors have declared no conflicts of interest.