Abstract 838P
Background
PD1 has become 1st line therapy for advanced cSCC however most pts have innate resistance (IR; upfront PD or PD after <6 months (mo) of stable disease [SD]) or acquired resistance (AR; PD after complete/partial response [CR/PR] or SD>6 mo). We aim to: (1) evaluate patterns of response/PD to PD1 therapy; (2) define a clinical predictive model of upfront PD; (3) study the management following PD to PD1.
Methods
Advanced cSCC pts treated with PD1 therapy at 8 international centres were included. Demographics, disease characteristics, full blood count, nature of PD, subsequent treatments and outcomes were examined. Multivariate analysis and backward elimination technique were used to build a model to predict upfront PD.
Results
115 advanced cSCC pts were included; 89 (77%) were male, median (med) age was 79 years (range 42 - 94). 25 pts (22%) had a history of a malignancy other than complex skin cancer and 10 (9%) pts were immunosuppressed. 33 (29%) pts had visceral metastases (mets); 19 (17%) lung, 17 (15%) bone and 3 (3%) liver mets. With a med follow-up of 17 mo (95% CI, 15 -20), the response rate was 66% (n=76; 36% [n=41] CR). 17 pts (15%) had upfront PD, and the combination of clinical features (age, immunosuppression, primary site, white cell count, neutrophils, and monocytes) accurately identified these pts (AUC 73.6; 95% CI, 60.1 – 87.0). Site-specific CR/PR was most common in subcutaneous (subcut; 67%) and lymph node (LN; 67%) mets, while site-specific PD was most common in bone (18%) mets. 24-mo PFS and OS were 62% (95% CI, 52-74%) and 68% (95% CI, 59-80%), respectively. From 34 (30%) progressing pts, 20 (59%) had IR and 14 (41%) had AR. 22 (65%) had further therapy, from which 16 (73%) had systemic +/- local therapy. Cetuximab was the most common systemic therapy (31%; n=5) and 4 pts responded. 4 pts (25%) were re-challenged PD1 and only 1 patient responded.
Conclusions
PD-1 demonstrated high subcut/LN response but poor response in bone cSCC mets. The combination of clinical features accurately predicted upfront PD, and although numbers were low, cetuximab demonstrated activity as subsequent therapy for these pts following PD1.
Clinical trial identification
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Bohne: Financial Interests, Personal, Funding, Travel grant: Sun Pharma, Pierre Fabre, BMS. C. Gaudy Marqueste: Financial Interests, Personal, Other, Travel support: BMS, MSD; Financial Interests, Personal, Advisory Board: BMS, MSD; Non-Financial Interests, Personal, Principal Investigator: BMS, MSD, Sanofi, Regeneron, Incyte, Pierre Fabre, Kartos, Replimune, InflaRx. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Pfizer/Array, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; 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, Bio-AI Health; 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, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR; Other, Travel Support: MSD. R. Ladwa: Financial Interests, Personal, Funding, Honoraria: MSD, BMS, AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting: Roche, AstraZeneca; Financial Interests, Personal, Other, Travel/accommodation: MSD. W. Xu: Financial Interests, Personal, Invited Speaker: Merck Serono, MSD, AZD; Financial Interests, Personal, Advisory Board: Merck Serono, MSD, Novartis; Financial Interests, Personal, Research Grant: Merck Serono; Financial Interests, Personal, Other, Conference Support: AZD. J.J. Grob: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Roche, Pierre Fabre, Novartis, Pfizer, Sanofi, Philogen, Iteos Therapeutics, Sunpharma; Financial Interests, Personal, Invited Speaker: BMS, Novartis, Pierre Fabre, Sanofi, Novartis; Financial Interests, Institutional, Research Grant: Pierre Fabre. A. Hauschild: Financial Interests, Personal, Advisory Board: BMS, MSD, Philogen, Pierre Fabre, Regereron, Roche, Sanofi, Novartis, Eisai, Immunocore, Replimune, Seagen; Financial Interests, Personal, Invited Speaker: MerckPfizer; Financial Interests, Institutional, Invited Speaker: BMS, MSD, Pierre Fabre, Amgen, Regeneron, Roche, Novartis. A.M. Menzies: Financial Interests, Personal, Advisory Board, advisory board: BMS, MSD, Novartis, Roche, Pierre-Fabre, QBiotics. 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. M.S. Carlino: Financial Interests, Personal, Advisory Role: Amgen, BMS, Eisai, Ideaya, MSD, Nektar, Novartis, Oncosec, Pierre Fabre, Qbiotics, Regeneron, Roche; Financial Interests, Personal, Funding, Honoraria: BMS, MSD, Novartis. I. Pires da Silva: Financial Interests, Personal, Funding, Travel Support: BMS; Financial Interests, Personal, Funding, Travel support: MSD; Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Novartis. All other authors have declared no conflicts of interest.