396O - Health-related quality of life (HRQoL) in patients (pts) treated with pembrolizumab (pembro) vs chemotherapy as first-line treatment in microsatellite instability-high (MSI-H) and/or deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC): Phase III KEYNOTE-177 study

Background

Pembro monotherapy significantly improved PFS vs standard of care (SOC) chemotherapy as first-line treatment in pts with MSI-H or dMMR mCRC in the phase III KEYNOTE-177 (NCT02563002) study. HRQoL results are reported.

Methods

Pts with confirmed MSI-H/dMMR mCRC with no prior systemic therapy for mCRC were randomized 1:1 to pembro 200 mg Q3W for up to 2 y or investigator’s SOC choice of mFOLFOX6 or FOLFIRI Q2W ± bevacizumab or cetuximab. EORTC QLQ-C30, EORTC QLQ-CR29, and EQ-5D-3L were administered at baseline and at various time points up to 1 y or end of treatment, whichever came first, and at 30 days after treatment discontinuation. Data from pts receiving ≥1 dose of study treatment and completing ≥1 HRQoL assessment were analyzed. Least-squares mean (LSM) score change from baseline to prespecified wk 18, 95% CI, and nominal 2-sided P values were calculated. Time to deterioration (TTD; ≥10-point decline from baseline) was assessed by Kaplan-Meier method and Cox regression model. HRs, 95% CIs, and nominal 1-sided P values are provided.

Results

Data for 294 pts (152, pembro; 142 SOC) were available for HRQoL analyses. Compliance at baseline was >90% in pembro and SOC arms for all 3 questionnaires and remained high at wk 18 (>85% and >75%, respectively). LSM change from baseline to wk 18 showed clinically meaningful improvement in QLQ-C30 global health status (GHS)/QoL (LSM difference: 8.96; 95% CI, 4.24-13.69; P=0.0002) and EQ-5D VAS (LSM difference: 7.38; 95% CI, 2.82-11.93; P=0.0016) for pts receiving pembro vs SOC. Prolonged TTD for pts receiving pembro vs SOC was observed for GHS/QoL (HR, 0.61; 95% CI, 0.38-0.98; P=0.0195), physical functioning (HR, 0.50; 95% CI, 0.32-0.81; P=0.0016), social functioning (HR, 0.53; 95% CI, 0.32-0.87; P=0.0050), and fatigue (HR, 0.48; 95% CI, 0.33-0.69; P≤0.0001).

Conclusions

Pembro monotherapy demonstrated clinically meaningful improvements in HRQoL vs SOC chemotherapy in pts with previously untreated MSI-H/dMMR mCRC.

Clinical trial identification

NCT02563002.

Editorial acknowledgement

Medical writing and/or editorial assistance provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA) and funded by Merck Sharp & Dohme Corp.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

T. André: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol Myers-Squibb; Honoraria (self): Chugai; Honoraria (self): GSK; Honoraria (self): Pierre Fabre; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche/Vantana; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Servier; Advisory/Consultancy: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Gritstone Oncology; Advisory/Consultancy: Halliodx; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Sharp & Dohme Corp; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Tesaro; Non-remunerated activity/ies, Participant of the Scientific committee : ARCAD foundation and GERCOR group. M. Amonkar: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. J. Norquist: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. K-K. Shiu: Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self): Guardant Health; Honoraria (self): Innovent Biologics; Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck KGaA; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (self): Servier; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Gilead; Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Innovent Biologics. T.W. Kim: Research grant/Funding (institution): Merck Serono, AstraZeneca, Pfizer. B.V. Jensen: Research grant/Funding (institution): Merck Sharp & Dohme Corp.. L.H. Jensen: Research grant/Funding (institution): MSD; Research grant/Funding (institution): 2cureX; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): BMS. C.J. Punt: Advisory/Consultancy: Bayer; Advisory/Consultancy: Nordic Pharma; Advisory/Consultancy: Servier. R. Garcia-Carbonero: Honoraria (self), Speaker Bureau/Expert testimony: AAA, Advanz Pharma, Bayer, BMS, HMP, Ipsen, Merck, Midatech Pharma, MSD, Novartis, PharmaMar, Pfizer, Pierre Fabre, Roche, Sanofi and Servier; Research grant/Funding (self), Financial support to an investigator-initiated trial evaluating Axitinib in NETs and Nivolumab in NECs: Pfizer, BMS; Research grant/Funding (institution), Institutional support for the conduct of clinical trials or for molecular diagnostic platforms: ARMO Biosciences, Astrazeneca, Pfizer, Novartis, Ipsen, Roche, Pharmacyclics, Boston Biomedicals, Merck, MSD, Amgen, Sanofi, Bayer, Bristol-Myers-Squibb, Boerhringer, Sysmex, Gilead Sciences, Servier, Adacap, VCN, Lilly, Pharmamar; Leadership role, Non-remunerated activity/ies, Member of the Executive Committee of the Spanish Neuroendocrine Tumor Cooperative Group (GETNE), Member of the Executive Committee of the European Society of Neuroendocrine Tumors (ENETS), Member of the Scientific Advisory Group for Oncology (SAG-O) of the European Medicines Agency (EMA) (2008-2017): GETNE, ENETS, SAG-O, EMA. I. Sevilla: Advisory/Consultancy: Ipsen, Pfizer, Syrtex, Amgen, Pharmamar; Speaker Bureau/Expert testimony: AAA, Sanofi, Novartis. C. de la Fouchardiere: Advisory/Consultancy: Roche, Pierre Fabre Oncologie, MSD, Eisai, Bayer; Travel/Accommodation/Expenses: Amgen, Eisai, BMS, Roche. F. Rivera: Advisory/Consultancy: MSD, Roche, Merck-Serono, Sanofi, BMS, Servier, Lilly, Amgen, Bayer, Celgene; Travel/Accommodation/Expenses: MSD, Roche, Merck-Serono, Sanofi, BMS, Servier, Lilly, Amgen, Bayer, Celgene. E. Elez: Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Hoffmann-La Roche, Servier, Amgen, Array Biopharma, Sanofi, Merck Sharp & Dohme Corp.; Research grant/Funding (institution): Array Biopharma, Merck Sharp & Dohme Corp., AbbVie, Amgen, GlaxoSmithKline, AstraZeneca, Bristol-Myers Squibb, Novartis, Boehringer Ingelheim, Hoffmann-La Roche; Research grant/Funding (self): Merck Sharp & Dohme Corp., Sanofi. L.A. Diaz: Advisory/Consultancy: Merck, Caris, Lyndra, Genocea Biociences, Illumina, Cell Design Labs, Neophore; Leadership role, Shareholder/Stockholder/Stock options, Officer/Board of Directors: PGDx; Shareholder/Stockholder/Stock options: Thrive, Neophore; Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Licensing/Royalties: Multiple, managed by Johns Hopkins and MSKCC COI; Officer/Board of Directors: Jounce Therapeutics; Spouse/Financial dependant: Amgen (equity). T. Yoshino: Research grant/Funding (institution): Novartis Pharma K.K.; Research grant/Funding (institution): MSD K.K.; Research grant/Funding (institution): Sumitomo Dainippon Pharma Co., Ltd.; Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Research grant/Funding (institution): Sanofi K.K.; Research grant/Funding (institution): Daiichi Sankyo Company, Limited; Research grant/Funding (institution): Parexel International Inc.; Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd.; Research grant/Funding (institution): GlaxoSmithKline K.K.. E. Van Cutsem: Advisory/Consultancy: Array, Astrazeneca, Bayer, Biocartis, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Pierre-Fabre, Roche, Servier, Sirtex, Taiho; Research grant/Funding (institution): Bayer, Boehringer Ingelheim, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier paid to the institution . P. Yang: Full/Part-time employment: MSD China Holding Co., Ltd.. M.Z.H. Farooqui: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. D. Le: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Research grant/Funding (self): BMS; Research grant/Funding (self): Aduro; Research grant/Funding (self): Medivir; Research grant/Funding (self): Curegenix; Research grant/Funding (self): Nouscom. All other authors have declared no conflicts of interest.