Abstract 871P
Background
An elevated NLR is associated with poor survival in pts with a variety of solid cancers, including those treated with immunotherapies. Based on literature, NLR ≥5 was identified as a cutoff for NLR elevation in the metastatic setting. This post hoc exploratory analysis from COMBI-i trial aimed at evaluating the potential predictive role of NLR in pts with BRAFV600–mutant advanced melanoma who received spartalizumab + dabrafenib + trametinib (Sparta-DabTram) versus (vs) placebo + dabrafenib + trametinib (placebo-DabTram).
Methods
All pts enrolled in COMBI-i trial (NCT02967692) were included in this analysis (Sparta-DabTram, n=267; placebo-DabTram, n=264). NLR values at baseline and subsequent treatment (Tx) cycles (up to cycle 7) were calculated and analyzed, along with other variables, and correlated with progression-free survival (PFS) using Kaplan–Meier curve.
Results
Baseline NLR values ranged from 2 to 4 for most of the pts in either of the Tx arms that reduced to 1-3 upon Tx. Survival tree analysis indicated that in pts receiving placebo-DabTram, the threshold NLR value obtained through mathematical model was associated with poor PFS outcome in pts with baseline NLR ≥1.693 (n=114) vs <1.693 (n=19). In pts with NLR ≥1.693, those with sum of the longest diameter (mm) ≥61 (n=43) had worst PFS outcome. Baseline NLR ≥1.693 was associated with poor PFS outcome in placebo-DabTram arm vs Sparta-DabTram arm. Literature-based cutoff for baseline NLR ≥5 was associated with shorter mPFS in placebo-DabTram arm (n=37) vs Sparta-DabTram arm (n=40; hazard ratio, 0.642 [95% confidence interval, 0.377-1.1]).
Conclusions
The findings from this study suggest that NLR is an independent factor predicting poor PFS outcome in pts with metastatic melanoma treated with the combination of immune checkpoint inhibitors and targeted therapy. Sparta-DabTram showed benefit in pts with poor prognostic factors, such as increased NLR and sum of target lesions compared to placebo-DabTram arm. The predictive value of NLR and the selected threshold will have to be validated in future studies.
Clinical trial identification
NCT02967692.
Editorial acknowledgement
Medical writing support/ editorial support was provided by Dr Moon Jain (Novartis Healthcare Pvt. Ltd.) which was funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, Novartis, MSD, Roche, Merck Serono, Sanofi, Merck, Novartis, BMS, MSD, 4SC, Nektar; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Roche, Merck Serono, Immunocore, 4SC, Pierre Fabre, Sanofi/Regeneron, Array Biopharma, Pfizer, Philogen, NEKTAR, Sandoz, Neracare; Financial Interests, Institutional, Research Grant: Novartis, BMS, MSD, Array/Pfizer; Financial Interests, Institutional, Invited Speaker: Novartis, BMS, MSD, Pierre Fabre, Sanofi, Roche, Philogen, 4SC, Nektar; Non-Financial Interests, Invited Speaker: EORTC-MG. K.T. Flaherty: Financial Interests, Personal, Other, Consultant: Takeda, Transcode Therapeutics, Novartis; Financial Interests, Personal, Invited Speaker: Clovis Oncology, Strata Oncology, Checkmate Pharmaceuticals, Kinnate BioPharma, Scorpion Therapeutics; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Strata Oncology, Checkmate Pharmaceuticals, Kinnate BioPharma, Scorpion Therapeutics, PIC Therapeutics, Apricity, Tvardi, xCures, Monopteros, Vibliome, ALX Oncology, Fog Pharma, Soley Therapeutics; Financial Interests, Personal, Ownership Interest: Nextech; Financial Interests, Institutional, Invited Speaker: Novartis, Pfizer. H.A. Tawbi: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Novartis, Genentech, Eisai, Karyopharm, Iovance, Pfizer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Merck, Novartis, Genentech; Financial Interests, Institutional, Funding: GSK, Eisai. C. Robert: Financial Interests, Personal, Advisory Board: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, AstraZeneca, Pfizer. P. Nathan: Financial Interests, Personal, Advisory Board: BMS, Immunocore, Novartis, Merck, Pfizer, 4SC; Financial Interests, Institutional, Other, research support: Immunocore; Financial Interests, Personal, Invited Speaker: novartis, 4SC; Financial Interests, Institutional, Invited Speaker: BMS, Novartis, Ipsen, Immunocore, Merck, Pfizer. 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. 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. 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, Personal, Advisory Board, Consultant and Advisory Role: Dohme, iTeos; 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. M. Mandala: Financial Interests, Personal, Advisory Board: MSD, Novartis, Sanofi, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sun Pharma. 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: Merck, Pfizer; Financial Interests, Institutional, Invited Speaker: BMS, MSD, Pierre Fabre, Amgen, Regeneron, Roche, Novartis. 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. R. Shah: Financial Interests, Institutional, Full or part-time Employment: Novartis; Financial Interests, Institutional, Stocks/Shares: Novartis. B. Gopal Sahoo: Financial Interests, Personal, Full or part-time Employment: Novartis. M.R. Lau: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. A. Ribas: Financial Interests, Personal, Advisory Board, Honoraria for consulting: Amgen, Apexigen, AstraZeneca, Merck, Novartis, Sanofi, Vedanta; Financial Interests, Personal, Advisory Board, Member of the Scientific Advisory Board: 4C Biomed, Apricity, Appia, Arcus, Compugen, Highlight, Immpact, ImaginAb, Immunesensor, Inspirna, Lutris, MapKure, Merus, PACT Pharma, Pluto, Synthekine, Tango; Financial Interests, Personal, Invited Speaker, Member of the Board of Directors: Arcus, Lutris, PACT Pharma; Financial Interests, Personal, Stocks/Shares, Stock ownership: 4C Biomed, Apricity, Appia, Arcus, Compugen, Highlight, ImaginAb, Immpact, Immunesensor, Inspirna, Isoplexis, Lutris, MapKure, Merus, Pluto, Synthekine, PACT Pharma, Tango, Advaxis, CytomX, RAPT, Kite-Gilead; Financial Interests, Personal, Invited Speaker: Arsenal Bio; Financial Interests, Institutional, Funding: Agilent, Bristol Myers Squibb.