LBA41 - Long-term survival with neoadjuvant therapy in melanoma: Updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC)

Background

Neoadjuvant therapy is the standard of care for resectable stage ≥IIIB melanoma. In 2021, the International Neoadjuvant Melanoma Consortium published a pooled analysis of 196 melanoma pts treated with neoadjuvant immunotherapy (ICI) or BRAF/MEK targeted therapy. Here, we provide a survival update of an expanded cohort.

Methods

Clinical, radiographic, histopathological, and survival data were collated for pts with resectable stage ≥IIIB melanoma who received neoadjuvant therapy in a clinical trial or routine care. Outcomes included major pathological response (MPR) rate, event-free survival (EFS; progression prior to surgery, recurrence post-surgery or death), and recurrence-free survival (RFS).

Results

Data was retrieved from 818 pts with stage ≥IIIB melanoma; 633 (77%) trial pts and 185 (23%) real-world pts. Median age 59 yrs (range, 18–92), 38% females, 45% IIIB, 38% IIIC, 2% IIID, 11% IIIB–D undefined, and 2% IV. Median follow-up was 3.0 yrs (range, 0.05–11). Pts received neoadjuvant ICI (N=610; 169 PD1 alone, 351 PD1+CTLA4, 59 PD1+LAG3, 27 PD1+other IO, 4 CTLA4 alone), BRAF/MEK (N=88), or ICI + Target Therapy (TT) (N=120). The MPR and RFS rates (for pts who underwent TLND or index node resection), and EFS rates (for total population) differed by treatment regimen (Table); OS data is still maturing. Within the ICI cohort, 3-yr EFS was 64% (95% CI 55–7367) with PD1 alone, 76% (95% CI 72–81) with PD1+CTLA4, and 82% (95% CI 70–95) with PD1+LAG3. For pts with PD1+other IO (median follow-up, 1.7 yrs [range, 0.7–3.2]), 1.5-yr EFS was 95% (95% CI 86–100). Additional correlations will be presented. Table: LBA41

* ICI, 562 (92%); BRAF/MEK, 88 (100%); ICI + TT, 118 (98%).

Conclusions

Neoadjuvant combination ICI provides an unprecedented and lasting survival benefit to pts with resectable stage ≥IIIB melanoma, particularly those who achieve MPR. Those with pNR, and likely pPR, will need alternative approaches.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Melanoma Institute Australia.

Funding

Has not received any funding.

Disclosure

G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, BioNTech SE, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG, Highlight Therapeutics S.L., IOBiotech, Immunocore Ireland Limited, Innovent Bioilogics USA Inc, Merck Sharp & Dohme, Novartis Pharma AG, PHMR Limited, Pierre Fabre, Regeneron Pharmaceuticals Inc, Scancell Limited, SkylineDX B.V.; Non-Financial Interests, Principal Investigator, GL is PI on over 30 clinical trials: GL is PI on over 30 clinical trials. R.N. Amaria: Financial Interests, Institutional, Coordinating PI: Merck, Bristol Myers Squibb, OnKure, Erasca, KSQ; Financial Interests, Institutional, Local PI: Roche; Financial Interests, Institutional, Trial Chair: Obsidian. I.V. Samoylenko: Financial Interests, Personal, Invited Speaker: Roche, PierreFarbre, Novartis, Biocad, R-pharm, Swixx. 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: Pfzer; 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. I. Pires da Silva: Financial Interests, Personal, Invited Speaker: BMS, MSD, Roche, Novartis; Financial Interests, Personal, Other, Travel Support: BMS, Roche; Financial Interests, Personal, Advisory Board: MSD. H.A. Tawbi: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Novartis, Genentech, Eisai, Karyopharm, Iovance, Pfizer, Jazz Pharmaceuticals; Financial Interests, Institutional, Trial Chair: Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Merck, RAPT Pharmaceuticals; Financial Interests, Institutional, Steering Committee Member: Novartis, Genentech; Financial Interests, Institutional, Funding: GSK, Eisai. M.S. Block: Financial Interests, Institutional, Research Grant: Alkermes, Bristol Myers Squibb, Genentech, Merck, nFerence, Pharmacyclics, Regeneron, Sorrento Therapeutics, TILT Biotherapeutics, Transgene, Viewpoint Molecular Therapeutics; Non-Financial Interests, Advisory Role: Sorrento Therapeutics, TILT Biotherapeutics, Viewpoint Molecular Therapeutics. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, Novartis, Merck Serono, Sun Pharma, Sanofi, Sandoz, Immunocore, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant, Advisory Role and Travel support: MSD, Pierre Fabre; Financial Interests, Personal, Other, Consultant and Advisory Role.Travel support: Pfizer/Array; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Consultant Role: Pfizer, 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: ValoTx; Financial Interests, Personal, Advisory Board, Consultant and Advisor role.Travel support: Replimmune; Financial Interests, Personal, Advisory Board, Advisor role: Bayer; Financial Interests, Personal, Other, Consultant and Advisory: Erasca; Financial Interests, Personal, Other, Consultant: Philogen; Financial Interests, Personal, Advisory Board: BionTech, Anaveon; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; 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, AIOM, SMR. A.C.J. van Akkooi: Financial Interests, Institutional, Advisory Board: Amgen, Bristol Myers Squibb, Novartis, MSD - Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC, Provectus; Financial Interests, Personal, Advisory Board: Neracare, SkylineDx; Financial Interests, Institutional, Research Grant, NIVEC study: Amgen; Financial Interests, Institutional, Research Grant: Merck-Pfizer. A.M. Menzies: Financial Interests, Personal, Advisory Board, advisory board: BMS, MSD, Novartis, Roche, Pierre-Fabre, QBiotics. All other authors have declared no conflicts of interest.