1104P - Efficacy of immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD1 treatment: A EUMelareg real-world evidence study

Background

Adjuvant immune checkpoint inhibition (ICI) with anti-PD1 antibodies in high-risk resected melanoma has been shown to improve recurrence-free survival by about 50 percent. It is unclear, whether adjuvant pre-treatment with anti-PD1 antibodies would impair response to ICI in metastatic patients with recurrence after adjuvant ICI.

Methods

From the adjuvant study platform of the European Melanoma Treatment Registry (EUMelaReg) we analysed cases with recurrence following adjuvant anti-PD1 ICI. In those, receiving ICI in the first-line setting, response rates and progression-free survival were compared to patients selected from the EMelaReg database by matching for relevant prognostic factors in the first-line non-adjuvant setting.

Results

A total of 389 melanoma patients with first-line ICI after failure from adjuvant anti-PD1 antibody treatment could be matched 1:1 for several prognostic covariates to first-line ICI cases without adjuvant pre-treatment. Overall response rate was significantly lower after adjuvant anti-PD1 treatment failure (32.9% vs. 40.0%) and progression free survival was 4.6 months for patients with adjuvant pre-treatment as compared to 10.1 months for PD1-naive patients (p<0.0001). This contrast was independent from usage of single agent anti-PD1 or combined ICI with anti-PD1 and anti-CTLAE4 in the first-line setting.

Conclusions

Adjuvant pre-treatment with anti-PD1 antibodies was related to an inferior response and progression-free survival in patients with metastatic or non-resectable melanoma receiving ICI in the first-line setting.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The European Melanoma Treatment Registry.

Funding

Merck/MSD, BMS, Novartis.

Disclosure

M. Weichenthal: Financial Interests, Personal, Advisory Board: MSD. D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, Novartis, MSD, Roche, Merck Serono, Sanofi; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Immunocore, Pierre Fabre, Sanofi/Regeneron, Pfizer, Philogen, NeraCare; 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. L. Bastholt: Non-Financial Interests, Advisory Role, Scientific committee under Danish Medicines Agency regarding new treatments of melanoma, skin cancer and thyroid cancer: Danish Medicines Agency. I. Gavrilova: Financial Interests, Advisory Board: MSD, Roche, Merck, Novartis, BMS, Sanofi. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, Ipsen, Merck Sharp & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Immunocore, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Scenic; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharp & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Editor-in-Chief IOTECH: ESMO; Other, Editorial Board ESMO Open: ESMO; Other, Editorial Board: Kidney Cancer. J. Mangana: Financial Interests, Advisory Board: Merck, Pfizer, MSD, Novartis, Roche, Pierre Fabre, Amgen, BMS. E. Espinosa: Financial Interests, Personal, Advisory Board: BMS, MSD; Financial Interests, Personal, Invited Speaker: BMS, MSD, Pierre Fabre, Novartis. I. Svane: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: MSD, Pierre Fabre, Novartis, Roche, BMS; Financial Interests, Personal, Writing Engagement: MSD; Financial Interests, Personal, Stocks/Shares, Cofounder and Founder warrents: IO Biotech; Financial Interests, Institutional, Research Grant: Adaptimmune, Enara Bio, Lytix Biopharma, TILT Biotherapeutics; Financial Interests, Institutional, Funding: Evaxion; Non-Financial Interests, Principal Investigator: BMS, Roche, TILT Biotherapeutics, Lytix Biopharma, Novartis. E. Ellebæk: Financial Interests, Personal, Invited Speaker: Pierre Fabre, BMS, Novartis, MSD, Pfizer; Other, Travel and conference expenses: MSD, Pierre Fabre. P. Mohr: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck Sharp & Dohme, Merck Sharp & Dohme, Novartis, GSK, Pierre Fabre, Sanofi; Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Merck 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. N. Asher: Financial Interests, Advisory Board: Medison, BMS, MSD, Novartis, NucleAI, Teva, OncoHost. R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, CatalYm, Second Genome, Regeneron, Alligator, MaviVAX SA, touchIME, T3 Pharma, Pfizer, Simcere. C. Gaudy Marqueste: Financial Interests, Advisory Board: Pierre Fabre, BMS, MSD. F. Aya: Financial Interests, Advisory Board: Novartis, MSD. H. Gogas: Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Sanofi; Financial Interests, Personal, Invited Speaker: MSD, BMS, Novartis, Pierre Fabre, Sanofi; Financial Interests, Steering Committee Member: Amgen, Replimune; Financial Interests, Institutional, Local PI: Amgen, MSD, BMS, Replimune, Iovance, Bayer; Financial Interests, Institutional, Research Grant: BMS, Pfizer, Lilly, Pierre Fabre. C. Lebbe: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre; Financial Interests, Personal, Funding: Roche, Bristol Myers Squibb; Non-Financial Interests, Advisory Role: Bristol Myers Squibb, MSD, Novartis, Amgen, Roche, Merck Serono, Sanofi, Pierre Fabre; Other, Honoraria, Speaker's Bureau, Research funding: Roche; Other, Honoraria, Speaker's bureau, Travel, Accommodation, Expenses, Research funding, Board: Bristol Myers Squibb; Other, Honoraria, Speaker's bureau, Travel, Accommodations, Expenses, Board: Novartis, MSD; Other, Honoraria, Speaker's bureau: Amgen; Other, Honoraria, Travel, Accommodations, Expenses, Board: Pierre Fabre; Other, Honoraria: Pfizer; Other, Honoraria: Incyte; Other, Travel, accommodations, Expenses, Board: Sanofi; Other, Board: Avantis Medical Systems, Jazz Pharmaceuticals; Other, Participation on a Data Safety Monitoring Board or Advisory Board: InflaRx. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfizer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Member of Board of Directors: Polish Society of Surgical Oncology; Non-Financial Interests, Member of Board of Directors, President: Polish Oncological Society. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant and Advisory Role, Travel support: Pfizer/Array; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna; Financial Interests, Personal, Other, Consultant role and travel support: Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory Role: iTeos; Financial Interests, Personal, Advisory Board, Consultant and Advisory role: ValoTx; Financial Interests, Personal, Advisory Board, Consultant and Advisor role. Travel support: Replimune; Financial Interests, Personal, Advisory Board, Advisor role: Bayer; Financial Interests, Institutional, Funding, Clinical Trial: Pfizer/Array, Roche Genentech, Sanofi; Financial Interests, Personal, Advisory Board: Erasca; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Member of Board of Directors, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, SMR, AIOM. All other authors have declared no conflicts of interest.