1106P - Anti-PD-1 (PD1) monotherapy or in combination with anti-CTLA-4 for metastatic melanoma (MM) patients (pts) with liver metastases (mets)

Background

Liver mets have been associated with poor response and survival in pts with MM treated with PD1 alone or in combination with anti-CTLA-4 (ipilimumab; PD1+IPI). Whether these pts benefit from PD1+IPI over PD1 is unknown. In MM pts with liver metastases, we sought to: a) determine objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) to PD1 vs PD1+IPI, and b) identify clinical predictors of response and survival to PD1+/-IPI.

Methods

MM pts with liver mets treated with 1^st line PD1 or PD1+IPI were included. Demographics, patient and disease characteristics, baseline blood parameters and clinical outcomes were examined. Univariate and multivariate (MVA) analyses were performed to identify clinical predictors of response and survival.

Results

Of 533 MM pts treated with 1^st line PD1 or PD1+IPI; 284 (53%) had PD1 and 249 (47%) had PD1+IPI. PD1 group had more ECOG PS ≥1 (53% vs 34%), but less BRAF V600 mutation (15% vs 33%) and stage M1D (15% vs 31%). Median follow-up from commencement of PD1+/-IPI was 47 months (42–51); ORR was 41%, higher in PD1+IPI (47%) vs PD1 (35%) (p=0.0027). PFS and OS at 1 year were 68% and 40%, respectively; non statistically higher with PD1+IPI (69%/43%) vs PD1 (67%/38%) (p>0.05). However, on MVA with multiple imputation for missing values and adjusting for predefined variables including age, gender, melanoma subtype (cutaneous non-acral, acral and mucosal), mutation status, ECOG PS, LDH and M1 substage (M1c versus M1d), PD1+IPI was associated with higher ORR (OR 2.21, 1.46 – 3.36; p<0.001), PFS (HR 0.73, 0.57 – 0.92; p=0.009) and OS (HR 0.71, 0.54 – 0.94; p=0.018) compared to PD1. Age (ORR, PFS), ECOG PS (OS), LDH (PFS, OS), M1 substage (ORR, PFS, OS), mutation status (PFS), melanoma subtype (OS) were also independent predictors of response and/or survival. Most pts ceased treatment due to progression (262 [53%]), and more pts stopped treatment due to toxicity in the PD1+IPI (n=77, 31%) vs PD1 (n=36, 14%) group.

Conclusions

In pts with liver metastases, 1^st line PD1+IPI showed higher ORR and improved survival compared with PD1 alone. These data will help guide treatment selection for pts with melanoma liver metastases.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

I. Pires da Silva: Financial Interests, Personal, Invited Speaker: BMS, MSD, Roche; Financial Interests, Personal, Other, Travel Support: BMS, Roche. S. Ugurel-Becker: Financial Interests, Personal, Research Funding: Bristol Myers Squibb, Merck Serono; Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, Novartis; Financial Interests, Personal, Other, meeting and travel support: Almirall, Bristol Myers Squibb, IGEA Clinical Biophysics, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sun Pharma. M. Carlino: Financial Interests, Personal, Advisory Board: Amgen, BMS, Eisai, IDEAYA, MSD, Nektar, Novartis, OncoSec, Pierre Fabre, QBiotics, Regeneron, Roche, Merck, Sanofi; Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis. A.M. Menzies: Financial Interests, Personal, Advisory Board, advisory board: BMS, MSD, Novartis, Roche, Pierre Fabre, QBiotics. M. Weichenthal: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme, Roche, Novartis, Bristol Myers Squibb, Sanofi; Financial Interests, Personal, Advisory Role: Sun Pharma, Pierre Fabre; Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme, Millennium, Bristol Myers Squibb, Johnson & Johnson, Novartis. P. Mohr: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Merck Sharp & Dohme, Roche/Genentech, Novartis, Amgen, Pierre Fabre, Merck, Sanofi; Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme, Bristol Myers Squibb, Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Amgen, Roche, Sun Pharma, Sanofi. R. Gutzmer: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Merck Sharp & Dohme, Roche/Genentech, Novartis, Merck Serono, Almirall Hermal GmbH, Amgen, Sun Pharma, Pierre Fabre, Sanofi, Immunocore, 4SC; Financial Interests, Institutional, Research Funding: Pfizer, Novartis, Johnson & Johnson, Amgen, Merck Serono, Sun Pharma, Sanofi; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb, Roche, Merck Serono, Pierre Fabre, Sun Pharma. A.M. Arance Fernandez: Financial Interests, Personal, Advisory Board, Consultant /Advisory/Speaker/Travel, Accommodation, Expenses/: Pierre Fabre, Novartis, Roche, BMS, MSD, Merck, Sanofi; Financial Interests, Institutional, Other, Research Funding: Pierre Fabre, Novartis, MSD, BMS, Merck, Roche, Sanofi, Amgen. D. Johnson: Financial Interests, Personal, Advisory Board: BMS, Catalyst Biopharma, Iovance, Jansen, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, OncoSec, Pfizer, Targovax, Teiko; Financial Interests, Personal, Funding: BMS, Incyte. P. Lorigan: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Pierre Fabre, BMS, MSD, Melagenix GmbH, Ultimovacs, MLA Diagnostics; Financial Interests, Personal, Research Funding: BMS, Pierre Fabre. 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. G.V. Long: Financial Interests, Personal, Speaker, Consultant, Advisor: Agenus, Amgen, Array Biopharma, Boehringer Ingelheim, BMS, Evaxion Biotech, Hexal AG, Highlight Therapeutics, Innovent Biologics, MSD, Novartis Pharma, OncoSec, PHMR, Pierre Fabre, Provectus, QBiotics, Regeneron. All other authors have declared no conflicts of interest.