2O - Health-related quality of life (HRQoL) with first-line (1L) nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC):

Background

NIVO + IPI showed superior progression-free survival vs chemo in pts with centrally confirmed MSI-H/dMMR mCRC in the 1L setting at 31.5-mo median follow-up (HR 0.21; 97.91% CI: 0.13, 0.35; P < 0.0001). We present the first HRQoL results from this follow-up.

Methods

HRQoL was assessed in all treated pts with centrally confirmed MSI-H/dMMR status using the EORTC QLQ-C30, QLQ-CR29, and EQ-5D-3L. Mixed-effects model for repeated measures provided least squares (LS) means and 95% CI estimates of change from baseline (BL); week (wk) 21 was prespecified as the primary timepoint of interest. Time to confirmed deterioration (TTCD) was estimated using Kaplan-Meier product limit methods.

Results

Of 245 pts treated with NIVO + IPI (n = 170) or chemo (n = 75), 94–96% had BL HRQoL data. Global Health Status (GHS) differences between the NIVO + IPI and chemo groups exceeded the prespecified minimally important difference (MID) of 5.0 starting at wk 13 (LS mean difference [MD], 9.7; 95% CI: 3.6, 15.9). At wk 21, clinically meaningful HRQoL improvement (GHS and functional scales) and decrease in symptoms with NIVO + IPI vs chemo was noted (Table), indicating HRQoL benefits with NIVO + IPI vs chemo. There was a decreased risk of HRQoL deterioration with NIVO + IPI vs chemo (TTCD in GHS, HR 0.32; 95% CI: 0.18, 0.57). Additional data will be shared. Table: 2O

aPositive change = improvement

bNegative change = improvement

cPrespecified MID was reached

Conclusions

In pts with centrally confirmed MSI-H/dMMR mCRC, 1L NIVO + IPI improved HRQoL and reduced symptoms, with a decreased risk of HRQoL deterioration vs chemo.

Clinical trial identification

NCT04008030.

Editorial acknowledgement

Writing and editorial assistance were provided by Dhivya Ramalingam, PhD, of Parexel, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

S. Lonardi: Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, Lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi Sankyo, Bristol Myers Squibb, Astellas, GSK, Takeda, Bayer; Financial Interests, Personal, Invited Speaker: Pierre Fabre, GSK, Roche, Servier, Amgen, Bristol Myers Squibb, Incyte, Lilly, Merck Serono, MSD; Financial Interests, Institutional, Invited Speaker: Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, Bristol Myers Squibb; Non-Financial Interests, Member of Board of Directors, Italian No-Profit Oncology Research Foundation supporting academic Clinical trials: GONO Foundation. T. André: Financial Interests, Personal, Advisory Board, Advisory Board on February 12, 2021: Astellas pharma; Financial Interests, Personal, Advisory Board, Advisory Board on February 2021: Kaleido Biosciences; Financial Interests, Personal, Invited Speaker, and advisory board 2021: Amgen; Financial Interests, Personal, Invited Speaker, symposium December 2020: AstraZeneca; Financial Interests, Personal, Advisory Board, and consultant fees and consultant contract 2021 and 2022: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Advisory board in January 2020: Clovis; Financial Interests, Personal, Advisory Board, Advisory board in January 2020: Gritstone Oncology; Financial Interests, Personal, Advisory Board, Advisory board 2020: HalioDX; Financial Interests, Personal, Advisory Board, and consultant fees/consultant contract and invited speaker: MSD Oncology; Financial Interests, Personal, Invited Speaker, and other: Pierre Fabre; Financial Interests, Personal, Invited Speaker, in an symposium in 2020: Roche; Financial Interests, Personal, Invited Speaker, in a meeting in 2019: Ventana; Financial Interests, Personal, Invited Speaker, In an educational meeting in 2019: Sanofi; Financial Interests, Personal, Advisory Board, in a symposium in 2020: Servier; Financial Interests, Personal, Expert Testimony, Consultant with personal fees and invited speaker: Servier; Financial Interests, Personal, Advisory Board, in 2019: GSK; Financial Interests, Personal, Invited Speaker, in 2020 and 2021: GSK; Financial Interests, Personal, Invited Speaker, Virtual symposium, Lecture 1, MSI-H CRC: Implementation of Immunotherapy in clinical practice (on July 2, 2021): MSD Oncology; Financial Interests, Personal, Invited Speaker, June 2022: Sanofi; Financial Interests, Personal, Advisory Board, Contract 2021, 2022, 2023: Merck & Co., Inc; Financial Interests, Personal, Advisory Board, Contract 2019, 2020, 2021, 2022: BMS; Financial Interests, Personal, Advisory Board, Contract 2021: Gritstone Oncologie; Financial Interests, Personal, Invited Speaker, June 2022 and June 2023 during ESMO GI meeting: Seagen; Financial Interests, Personal, Invited Speaker, Contract of consulting 2021 and 2022 and 2023: MSD Oncology; Financial Interests, Personal, Advisory Board, September 2022: GSK, Seagen; Financial Interests, Personal, Invited Speaker, Contract of consulting 2022 and 2023: GSK; Financial Interests, Personal, Invited Speaker, Contract of consulting 2022: Nordic Pharma; Financial Interests, Personal, Invited Speaker, October 2022: Merck Serono; Financial Interests, Personal, Other, Educational in 2022: Roche; Financial Interests, Personal, Other, Contract of consulting 2020, 2021, 2022,2023: Servier; Financial Interests, Personal, Advisory Board, Gilead Sciences Global GI Advisory Board on January 18, 2023: Aptitude Health, Gilead; Financial Interests, Personal, Other, Consultant like member of the SGNTUC-029 Steering Committee (the “Steering Committee”) Services related to the Company’s Study titled “An Open-label Randomized Phase 3 Study of Tucatinib in Combination with Trastuzumab and mFOLFOX6 versus mFOLFOX6 given with or without either Cetuximab or Bevacizumab as First-line Treatment for Subjects with HER2+ Metastatic Colorectal Cancer” (collectively, the “Services”). 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Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd., Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., Falco Biosystems Ltd. M. Dixon: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S.I. Blum: Financial Interests, Personal, Other, Employee: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Sims: Financial Interests, Personal, Invited Speaker, Funded Adelphi Values Ltd (my employer) to complete statistical analysis work relating to this abstract: Bristol Myers Squibb. R. Lawrance: Financial Interests, Personal, Funding, Funded Adelphi Values Ltd. (my employer) to complete statistical analysis work relating to this abstract: Adelphi Values Ltd.; Non-Financial Interests, Personal, Advisory Board, Director, PSI (Statisticians in Pharmaceutical Industry)Unpaid. Director June 2019- June 2023. This work is not related to this role: PSI. F. Taylor: Financial Interests, Personal, Full or part-time Employment: Adelphi. T. Chen, E. Cela, L. Jin: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. E. 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