1124P - Adjuvant treatment of patients with stage III melanoma: 4-year follow-up time of multicenter real-world study

Background

Adjuvant treatment with immune checkpoint inhibition (PD1) and targeted therapy (TT) with BRAF+MEK inhibitors has significantly improved recurrence-free survival (RFS) of stage III melanoma patients in clinical trials. We investigated adjuvant therapy in melanoma patients under real-world conditions.

Methods

In a prior analysis of this multicenter cohort study, we reported the treatment course, recurrence characteristics, subsequent management and outcomes of stage III melanoma patients receiving adjuvant therapy at 2 years of follow-up (FU) (Lodde et al, EJC 2023). Updated data at 4 years of FU are now presented with a focus on patients with BRAF-mutated melanoma.

Results

FU data of 589 stage III melanoma patients was available (41 stage IIIA, 218 IIIB, 309 IIIC, 21 IIID; 232 BRAF-mutated). 479 patients had received PD1 (81%), and 110 TT (19%; 47% of all BRAF-mutated patients). At a median FU of 48.1 months, 55% of PD1-treated patients (265/479; 53% of BRAF-mutated patients [65/122]) and 45% of TT-treated patients (49/110) had disease recurrence. Median RFS was 24.7 months for all PD1 patients (95% confidence interval [95% CI] 18.4−41.1) and was not reached for TT patients (95% CI 34.8-NR). 4-year RFS was 43% (95% CI 38.5-47.8) for PD1 patients and 53% (95% CI 43.6-63.3) for TT patients. Death from melanoma occurred in 21% (100/479) of PD1 patients and 13% (14/110) of TT patients. Among the BRAF-mutated patient cohort, risk of recurrence was greater for PD1 than TT (hazard ratio HR crude 1.57, 95% CI 1.09-2.26; HR adjusted for age, sex, and tumor stage, 1.73, 95% CI 1.20−2.50). No clinically meaningful difference was detected for melanoma-specific survival (HR crude 1.36, 95% CI 0.69-2.68; HR adjusted for age, sex, and tumor stage 1.49, 95% CI 0.75−2.95). Second recurrence-/progression-free survival (RPFS2) from start of first adjuvant treatment to second relapse/death was 27.6 months for BRAF-mutated PD1-treated patients (95% CI 16.5-not reached) and 31.7 months for TT patients (95% CI 24.0-NR).

Conclusions

RFS at 4 years was clearly better in TT-treated patients compared to all PD1-treated patients. Patients with BRAF-mutated melanoma had a significantly higher risk of relapse when treated with adjuvant PD1 than when treated with TT.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

E. Livingstone, G. Lodde.

Funding

Research funding from Novartis; German Research Foundation, RTG 2535, Knowledge- and data-driven personalization of medicine at the point of care.

Disclosure

E. Livingstone: Financial Interests, Personal, Advisory Board: Novartis, BMS, Sanofi, Sun Pharma, Recordati, MSD; Financial Interests, Personal, Invited Speaker: Novartis, BMS; Financial Interests, Personal, Other, Innvator´s Circle: Pierre Fabre; Non-Financial Interests, Principal Investigator: BMS, Novartis, Regeneron, MSD, Philogen, 4SC, Biontech, Immatics, Immunocore; Non-Financial Interests, Member: DeCOG, DKG; Other, Other, Travel expenses: Pierre Fabre, Sun Pharma. A. Forschner: Financial Interests, Institutional, Advisory Board: Novartis, MSD, BMS, Pierre Fabre, Immunocore; Financial Interests, Institutional, Invited Speaker: Immunocore, Novarits, BMS, Pierre Fabre; Financial Interests, Institutional, Research Grant: BMS Immunoncology; Non-Financial Interests, Member: ADO, DKG, PSO, DDG; Non-Financial Interests, Leadership Role: ADO Komitee Survivorship; Other, Other, congress participation including travel and hotel: Pierre Fabre. J.C. Hassel: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Sanofi, MSD, SunPharma, Amgen, GSK, Pierre Fabre, Immunocore, Delcath; Financial Interests, Institutional, Advisory Board: MSD, Novartis, BMS, Immunocore, Philogen, Sanofi; Financial Interests, Personal, Advisory Board: Pierre Fabre, SunPharma, GSK, Onkowissen, Pierre Fabre; Financial Interests, Institutional, Writing Engagement: BMS; Financial Interests, Institutional, Research Grant: BMS, SunPharma, Sanofi; Financial Interests, Institutional, Local PI: Philogen, Genentech, 4SC, BioNTech, Iovance, Pierre Fabre, Regeneron, Sanofi, Replimune, Immatics, MSD, Pfizer, Agenus; Financial Interests, Institutional, Coordinating PI: BMS, Immunocore, Novartis, Genmab, Seagan; Financial Interests, Personal, Steering Committee Member: Immunocore, IO Biotech; Non-Financial Interests, Leadership Role: DeCOG; Non-Financial Interests, Member: ASCO. I. von Wasielewski: Financial Interests, Personal, Advisory Board: BMS, MSD, Sanofi; Financial Interests, Personal, Invited Speaker: Stemline, Kyowa Kirin; Financial Interests, Personal, Other, Travel und Accomodation assist: Pierre Fabre. F. Meier: Financial Interests, Personal, Advisory Board: Bristol Myers Sqibb, Novartis, MSD, Sanofi, Philogen, Immunocore; Financial Interests, Personal, Invited Speaker: Sanofi, Immunocore. P. Mohr: Financial Interests, Personal, Advisory Board: Bristol Myers SquibbMerck Sharp & Dohme, Merck Sharp & Dohme, Novartis, GSK, Pierre Fabre, Sanofi; Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers SquibbMerck Sharp & Dohme, Merck Sharp & Dohme, Novartis, Roche, Pierre Fabre, Sanofi, Sun Pharma; Financial Interests, Institutional, Funding: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis; Non-Financial Interests, Principal Investigator: Bristol Myers Squibb, Merck Sharp & Dohme, Regeneron, Sanofi, Novartis, Sun Pharma. K.C. Kähler: Financial Interests, Advisory Board: BMS, MSD, Pierre Fabre, Roche, Immunocore, Regeneron, Sanofi-Aventis; Financial Interests, Local PI: MSD, Immunocore, BMS, Huya Biosciences, Roche, Sanofi-Aventis, Pierre Fabre. B. Schilling: Financial Interests, Personal, Invited Speaker: SUN Pharma; Financial Interests, Personal, Advisory Board: Sanofi, Pierre Fabre Pharma, Immunocore; Financial Interests, Institutional, Coordinating PI: Novartis. M. Erdmann: Financial Interests, Personal, Advisory Board, Clinical case presentation: Immunocore; Financial Interests, Personal, Invited Speaker, Presentation at workshop for nurses: Novartis; Financial Interests, Personal, Invited Speaker, Presentation at workshop as well as travel/meeting expenses: Pierre Fabre; Financial Interests, Personal, Other, travel expenses: Sanofi. C. Berking: Financial Interests, Personal, Advisory Board: BMS, MSD, InflaRx, Sanofi, Regeneron, Novartis, Pierre Fabre, Delcath, Immunocore; Financial Interests, Personal, Invited Speaker: BMS, Almirall, MSD, Immunocore, Pierre Fabre, Leo Pharma; Financial Interests, Institutional, Coordinating PI: Almirall; Financial Interests, Institutional, Local PI: InflaRx, Immunocore, IOBiotech, Kartos, MSD, Regeneron. S. Huning: Financial Interests, Personal, Advisory Board: Kyowa Kirin, BMS; Financial Interests, Personal, Invited Speaker: MSD, Novartis. H. Stege: Financial Interests, Advisory Board: BMS, MSD, Sun Pharma, Pierre Fabre. R. Gutzmer: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Pierre Fabre, Novartis, MSD, Merck Serono, Almirall, Immunocore, Delcath, KyowaKirin, Sanofi/Regeneron, SUN Pharma; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Pierre Fabre, Novartis, MSD, Merck Serono, Almirall, Sanofi/Regeneron, SUN Pharma; Financial Interests, Institutional, Research Grant: KyowaKirin, Almirall, SUN Pharma, Amgen, Sanofi/Regeneron, Merck Serono; Non-Financial Interests, Member of Board of Directors: DeCOG; Other, Other, Travel and meeting support: Pierre Fabre, SUN Pharma. A. Stang: Financial Interests, Invited Speaker: MedKom-Akademie GmbH 2021, OnkoUpdate 2023. A. Hauschild: Financial Interests, Personal, Advisory Board: BMS, MSD, Philogen, Pierre Fabre, Regeneron, Roche, Sanofi, Novartis, Eisai, Immunocore, Replimune, Seagen, Dermagnostix, Neracare, IO Biotech, Incyte, Highlight Therapeutics, Agenus, Xenthera; Financial Interests, Personal, Invited Speaker: Merck Pfizer; Financial Interests, Institutional, Local PI: BMS, MSD, Pierre Fabre, Amgen, Roche, Agenus; Financial Interests, Institutional, Coordinating PI: Regeneron, Novartis. L. Zimmer: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, MSD, SunPharma, Pierre Fabre, Sanofi; Financial Interests, Personal, Other, Travel Support: Bristol Myers Squibb, MSD, SunPharma, Pierre Fabre, Sanofi, Novartis, Amgen; Financial Interests, Personal, Invited Speaker: Novartis, MSD, Pierre Fabre, Roche; Financial Interests, Personal and Institutional, Research Grant: Novartis; Non-Financial Interests, Member: German Cancer Society, Dermatologic Cooperative Oncology Group. D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, MSD, Merck Serono, Sanofi, Neracare, SunPharma; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Immunocore, Pierre Fabre, Sanofi/Regeneron, Pfizer, Philogen, Neracare, InFlarX, BioAlta, Daiichi Sanyko, NoviGenix, Anaveon, AstraZeneca, PamGene, BioNTech, Immatics, CureVac, Erasca, Formycon, Replimune, Seagen, SunPharma, Ultimovacs; Financial Interests, Personal, Steering Committee Member: Novartis, BMS, MSD; Financial Interests, Institutional, Coordinating PI: Novartis, BMS, MSD, Pierre Fabre; Financial Interests, Institutional, Research Grant: BMS, MSD; Financial Interests, Institutional, Local PI: Sanofi, Philogen; Non-Financial Interests, Member of Board of Directors: EORTC-MG; Non-Financial Interests, Leadership Role, Founding member and SC chair: European Melanoma Registry (EuMelaReg). G.C. Lodde: Financial Interests, Advisory Board: Sun Pharma; Financial Interests, Sponsor/Funding: Pierre Fabre, Novartis, BMS; Financial Interests, Local PI: German Research Foundation. All other authors have declared no conflicts of interest.