Abstract 1050P
Background
Immune checkpoint inhibitors (ICI) have become a standard of care in oncology. However, little is known about their influence on the outcomes of subsequent treatment lines. We investigated the impact of prior exposure to ICI on the safety and efficacy of early-phase trial therapies.
Methods
Patients (pts) from phase I/II trials, treated for melanoma, lung, head and neck, urothelial bladder, and renal cell cancer were included. Group A pts were immuno-naïve whereas group B pts had received at least one prior line of ICI-based therapy. Phase I/II trials included treatments based on ICI (IO) and non-immunologic therapies (NON-IO). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and the advent of immune-related adverse events (irAE). We further assessed the prognostic value of the Royal Marsden Hospital (RMH) Score, Neutrophil/lymphocyte ratio (NLR) and Gustave Roussy Immune (GRIm) score.
Results
A total of 322 pts were included from 32 trials: 184 in group A and 138 in group B. The median number of prior lines was 1 [1-2] in group A and 3 [2-4] in group B. Administered therapies were classified as IO in 214 pts (132 in group A, 82 in group B) and NON-IO in 108 pts (52 in group A, 56 in group B). Pts from group B had a significantly shorter PFS (median [95%CI]: 82 days [61 – 91] vs. 156 days [117 – 193], HR: 1.75 [1.35 – 2.26], p<0.0001) and OS (338 [281 – 391] vs. 558 [397 – 806] days, HR: 1.78 [1.41 – 2.56], p <0.0001) than group A. PFS benefit in group B was confirmed in multivariate analysis (HR: 1.42 [1.06 – 1.91], p=0.02). Among pts treated with NON-IO, PFS was similar between groups A and B (p = 0.17). In pts treated with IO, PFS was shorter in group B than in group A, but similar to that of NON-IO therapies (p=0.95). Rate of IrAE was 14.6% in group B, 36.4% in group A (OR: 0.30 [0.15 – 0.60], p = 0.0005). The RMH score, NLR (median cut-off) and GRIm score significantly correlated with PFS in group A (p = 0.014, 0.004, and 0.0002, respectively) but not in group B (p = 0.18, 0.17, 0.17).
Conclusions
In this study, pre-exposure to ICI was associated with reduced efficacy of early-phase trial immune therapies although comparable to non-immunologic therapies benefit in our series of patients. Additionally, pre-exposed patients were less likely to develop irAE.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Gustave Roussy.
Funding
Has not received any funding.
Disclosure
R. Sun: Travel/Accommodation/Expenses: AstraZeneca. S. Champiat: Honoraria (self): Amgen, AstraZeneca, BMS, Janssen, MSD, Novartis, and Roche; Non-remunerated activity/ies, Sub investigator of clinical trials: for AbbVie, Aduro biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, AstraZeneca Ab, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines,; Research grant/Funding (institution): AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-remunerated activity/ies, Drug supply: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Lilly, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. J-M. Michot: Non-remunerated activity/ies, Principal/Sub investigator of clinical trials: AbbVie, Agios, Amgen, Argen-x, Astex, AstraZeneca, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Genentech, Janssen, Kyowa, Lilly, Lysarc, Lytix Biopharma, MedImmune, Roche, Sanofi, Xencor; Travel/Accommodation/Expenses: Celgene, Bristol-Myers Squibb, AstraZeneca, Janssen; Non-remunerated activity/ies, Drug supplied: AstraZeneca, Roche, Novartis, Gilead, Celgene, Bristol-Myers Squibb. C. Baldini: Advisory/Consultancy: BMS, AbbVie, AstraZeneca. A. Gazzah: Travel/Accommodation/Expenses: Boehringer Ingelheim, Novartis, Pfizer, Roche; Advisory/Consultancy: Novartis; Non-remunerated activity/ies, Principal/subinvestigator of clinical trials: Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boehringer Ingelheim, Bristol; Research grant/Funding (self): AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-remunerated activity/ies, Drug supplied: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Lilly, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. R. Bahleda: Non-remunerated activity/ies, Principal/Sub investigator of clinical trials: AbbVie, Aduro biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, AstraZeneca Ab, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boeh; Research grant/Funding (self): from AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi.; Non-remunerated activity/ies, Drug Supply: from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Lilly, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. P. Martin-Romano: Non-remunerated activity/ies, Principal/Sub investigator of clinical trials: AbbVie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Blueprint Medicine; Non-remunerated activity/ies, Drug supplied: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. A. Hollebecque: Honoraria (self): Amgen, Eisai, Servier; Advisory/Consultancy: AstraZeneca, Incyte, Debiopharm; Research grant/Funding (self): Incyte. A. Varga: Non-remunerated activity/ies, Principal/Sub investigator of clinical trials: AbbVie, Aduro biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, AstraZeneca Ab, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boeh; Research grant/Funding (self): AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-remunerated activity/ies, Drug supply: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Lilly, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche; Travel/Accommodation/Expenses: AstraZeneca, Boehringer Ingelheim. A. Marabelle: Non-remunerated activity/ies, Principal/Sub investigator of clinical trials: AbbVie, Aduro biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, AstraZeneca Ab, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boeh; Non-remunerated activity/ies, Drug supplied: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Lilly, MedImmune, Merck serono, NH TherAGuiX, Pfizer, Roche.; Research grant/Funding (institution): Merus, BMS, Boehringer Ingelheim, Transgene, Fondation MSD Avenir; Speaker Bureau/Expert testimony: Roche/Genentech, BMS, Merck (MSD), Merck Serono, AstraZeneca/MedImmune, Amgen, Sanofi. Scientific & Medical Consulting for Roche, Pierre Fabre, Onxeo, Eisai, Bayer, Genticel, Rigontec, Daichii Sankyo, Sanofi, BioNTech, Corvus, GLG, Deerfield, Guidepoint. C. Massard: Advisory/Consultancy: Amgen, Astellas, AstraZeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion; Non-remunerated activity/ies, Principal/sub-Investigator of ClinicalTrials: for AbbVie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveopharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boehringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 bi. All other authors have declared no conflicts of interest.