Abstract 63P
Background
TFS, a novel endpoint that can capture time periods of disease control and durability of clinical benefit following treatment (tx) discontinuation. TFS may be particularly appropriate in immunotherapy where some pts have shown continued benefit following a defined course of tx. Here we present TFS analysis with 4 y of follow-up in pts with mNSCLC treated with 1L NIVO + IPI + chemo or chemo alone in CM 9LA. As previously reported, CM 9LA significantly improved OS with NIVO + IPI + chemo vs chemo (HR 0.69 [96.71% CI 0.55-0.87]).
Methods
Analysis included all randomized pts who received NIVO + IPI (up to 2 y) + chemo (2 cycles; n = 361) or chemo (4 cycles; n = 358) up to 48 mo. TFS was defined as the restricted mean (r-mean) between Kaplan-Meier (KM) curves for time to tx cessation and time to subsequent tx/death. TFS was also divided into periods with/without ongoing grade ≥ 3 tx-related adverse events and estimated over 24-, and 48-mo periods from randomization.
Results
At 4 y, an estimated 21% of pts treated with NIVO + IPI + chemo were alive, and an estimated 17% were alive without any subsequent systemic tx. Of pts treated with chemo, OS rate of 16% was observed at 4 y, and 8% for those that were alive without any subsequent tx. Over the 48-mo period since randomization, for pts treated with NIVO + IPI + chemo vs chemo, r-mean OS was 22.2 vs 17.6 mo (difference 4.6 mo; 95% CI 2.19-7.01), and r-mean TFS was 7.5 vs 5.0 mo (difference 2.6 mo; 95% CI 1.05-4.16), which was 16% vs 10% of 48-mo period spent in TFS. Mean TFS with toxicity constituted a small proportion of the 48-mo period for both tx arms, resulting in r-mean TFS without toxicity of 6.8 vs 4.5 mo (difference 2.3 mo; 95% CI 0.76-3.79). Similar results were shown by tumor PD-L1 expression levels and will be presented. The proportion of mean time spent in TFS increased from 11% of 24-mo to 16% of 48-mo period in the NIVO + IPI + chemo arm, while decreased from 14% to 10% in the chemo arm.
Conclusions
In this CM 9LA analysis, 1L NIVO + IPI + chemo demonstrated an improvement in TFS with and without toxicity, regardless of tumor PD-L1 expression level, over 48 mo compared with chemo. These data reflect durable clinical benefit of NIVO + IPI + chemo following tx cessation.
Clinical trial identification
NCT03215706.
Legal entity responsible for the study
BristolMyers Squibb.
Funding
BristolMyers Squibb.
Disclosure
M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Merck, Novartis, Regeneron, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Biontech, Boehringer Ingelheim, Daiichi Sankyo, Gilead, MSD, Mirati, Pfizer, Regeneron, Roche, Sanofi; Financial Interests, Personal, Other, Member of DMSB: Daiichi Sankyo. M. Regan: Financial Interests, Personal, Advisory Board, Also invited speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Includes consulting.: Tolmar Pharmaceuticals; Financial Interests, Personal, Advisory Board: AstraZeneca, Tersera Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Bayer; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trial supported by company: Novartis; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials supported by company: Pfizer, Ipsen, TerSera; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trial drug supply from company: Roche; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials supported or drug supply from company: AstraZeneca; Financial Interests, Institutional, Other, Director of IBCSG Statistical and Data Management Center for IBCSG investigator-initiated clinical trials with funding from company: Debiopharm; Financial Interests, Institutional, Funding, IBCSG translational research collaboration: Biotheranostics; Non-Financial Interests, Personal, Advisory Role: Bristol Myers Squibb. D.P. Carbone: Financial Interests, Personal and Institutional, Research Grant, Grants or contracts from any entity: Merck to OSU.; Financial Interests, Personal and Institutional, Other, Consulting Fees: AbbVie, Arcus Biosciences, BMS, BMS Brazil, BMS Israel, BMS KK, Boehringer Ingelheim, Curio Science, Daiichi Sankyo Inc, Flame Biosciences, Genentech/Roche, GI Therapeutics (Intellisphere), GSK, InThought, Iovance Biotherapeutics, Janssen, JNJ, Merck, Mer; Financial Interests, Personal and Institutional, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal, Other, DSMBs: EORTC, AbbVie, Lilly; Financial Interests, Personal, Other, Adv Boards: AbbVie, Amgen, Arcus Biosciences, AstraZeneca, Cantargia (PPD), Daiichi Sankyo Inc, EMD Serono, Flame Biosciences, Iovance Biotherapeutics, Genentech, G1 Therapeutics, GSK, Gritstone Oncology, Janssen/JNJ, Jazz, Lilly, Merck, Merck KGgA, MSD, Mirati, Novo. S. Lu: Financial Interests, Institutional, Invited Speaker: Hansoh, AstraZeneca, Roche, Hengrui; Financial Interests, Institutional, Advisory Board: AdtraZeneca, Prizer, Boehringerlngelheim, Hutchison MediPharma, ZaiLab, GenomiCare, Yuhan Corporation, Menarini, InventisBio Co.Ltd, Roche, Simcere Zaiming Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui, Roche, Hansoh, BeiGene, Lilly Suzhou Pharmaceutical Co.Ltd; Financial Interests, Personal, Invited Speaker: FibroGen. T. John: Financial Interests, Personal, Invited Speaker, Speaker tour Vietnam: AstraZeneca; Financial Interests, Personal, Invited Speaker, CTIO: Merck Sharp Dohme; Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Bayer, Specialised Therapeutics; Financial Interests, Institutional, Advisory Board: Roche, Novartis, Pfizer, Amgen, Takeda, PharmaMar; Financial Interests, Personal, Other, Speaker/Chair: ACE Oncology. J. Penrod: Financial Interests, Personal and Institutional, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Full or part-time Employment: Bristol Myers Squibb. J. Li: Financial Interests, Personal and Institutional, Full or part-time Employment, BMS GBDS Market Access biostatistician: Bristol-Myers Squibb. Y. Yuan, J. Mahmood: Financial Interests, Personal and Institutional, Full or part-time Employment: Bristol Myers Squibb. A. Lee, L. Eccles, S. Ray: Financial Interests, Personal and Institutional, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Full or part-time Employment: Bristol Myers Squibb. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President. ASEICA (Spanish Association of Cancer Research): ASEICA; Financial Interests, Personal, Other, Foundation president: ONCOSUR; Financial Interests, Personal, Other, member: Small Lung Cancer Group.