1516P - Health-related quality of life (hrqol) analysis from KEYNOTE-859: First-line (1L) pembrolizumab (pembro) + chemotherapy (chemo) for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) adenocarcinoma

Background

In the phase III KEYNOTE-859 study (NCT03675737), 1L pembro + chemo significantly improved OS, PFS, and ORR vs placebo (pbo) + chemo regardless of PD-L1 expression and had a manageable AE profile in patients (pts) with locally advanced/metastatic HER2-negative G/GEJ adenocarcinoma. Prespecified exploratory HRQoL outcomes are reported.

Methods

HRQoL was assessed in treated pts who completed ≥1 HRQoL assessment using the EORTC QLQ-C30, EORTC QLQ-STO22, and EQ-5D-5L questionnaires. Least squares mean (LSM) changes from baseline (BL) to wk 18 in QLQ-C30 GHS/QoL; physical functioning (PF) and role functioning (RF) subscales; nausea/vomiting and appetite loss symptoms scales; QLQ-STO22 pain symptom scale; and EQ-5D-5L VAS were compared using a constrained longitudinal data analysis model (covariates: Tx by study visit interaction and stratification factors). Time to deterioration (TTD; ≥10-point decline from BL in a given scale/subscale) was estimated using the Kaplan-Meier method; between-arm difference (HR) was determined using a stratified Cox proportional hazards model.

Results

The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was wk 18. From BL to wk 18, LSM changes in QLQ-C30 GHS/QoL, PF, RF, nausea/vomiting, and appetite loss and EQ-5D-5L VAS were similar between arms; the QLQ-STO22 pain scale favored pembro + chemo (Table). TTD (HR; 95% CI) in QLQ-C30 GHS/QoL (0.87; 0.72-1.04), PF (0.91; 0.76-1.08), RF (0.90; 0.76-1.06), appetite loss (1.00; 0.82-1.22), and nausea/vomiting (0.95; 0.79-1.14) were similar between arms; the QLQ-STO22 pain scale favored pembro + chemo (0.76; 0.58-0.98).

Table: 1516P

Conclusions

HRQoL data from KEYNOTE-859, combined with efficacy and safety results, support a favorable benefit-to-risk profile for pembro + chemo as a new 1L Tx option for advanced HER2-negative G/GEJ adenocarcinoma.

Clinical trial identification

NCT03675737.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Obinna Ezeokoli, PhD, and Lauren D’Angelo, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. The authors thank Yanfen Guan (of Merck & Co.,Inc., Rahway, NJ, USA) for their assistance with this analysis.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

M.A. Lowery: Financial Interests, Personal, Invited Speaker, Educational session for trainees: Novartis; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board: Agios, Servier; Financial Interests, Institutional, Other, Educational Grant: Roche; Financial Interests, Institutional, Research Grant: Genuity Science; Non-Financial Interests, Principal Investigator: MSD, Basilea, Exelixis, Astellas; Non-Financial Interests, Principal Investigator, Clinical trial: Daiichi Sankyo, Zymeworks. L.S. Wyrwicz: Financial Interests, Personal, Advisory Board: BMS, Servier; Financial Interests, Personal and Institutional, Local PI: BMS, MSD, Servier, BeiGene, Roche, AstraZeneca; Financial Interests, Personal, Steering Committee Member: AstraZeneca. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, MSD; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. K. Shiu: Financial Interests, Personal, Invited Speaker, Educational Webinars on CRC and UGI cancer management with immunotherapy: BMS; Financial Interests, Personal, Advisory Board, Advisory Board on Regorafenib for chemorefractory mCRC in readiness for NICE application: Bayer; Financial Interests, Personal, Invited Speaker, Educational webinars on Pembrolizumab for MSI-High CRC, as well as OG cancers: MSD; Financial Interests, Personal, Advisory Board, For Pembrolizumab in CRC of OG cancers pre or NICE application or post NICE approval: MSD; Financial Interests, Personal, Invited Speaker, Webinars on updates on management of mCRC: Merck; Financial Interests, Personal, Advisory Board, On Mirati GI Global Advisory Board: Mirati Therapeutics; Financial Interests, Personal, Invited Speaker, To update company on indications/updates in landscape of immunotherapy and vaccines in GI cancers: Nouscom; Financial Interests, Personal, Advisory Board, Advisory on Cancer of Unknown Primary, new indications of molecular profiling usingFoundation Medicine 1: Roche; Financial Interests, Personal, Advisory Board, Advisory Board on Lonsurf for chemorefractory mCRC in readiness for NICE application: Servier; Financial Interests, Institutional, Local PI, For MATTERHORN Trial: AstraZeneca; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator on KEYNOTE 177, KEYNOTE 859, KEYNOTE 811, LEAP 17, MK1308A-008 trials: MSD; Financial Interests, Institutional, Research Grant, Chief Investigator of investigator initiated, MSD funded NEOPRISM-CRC trial: MSD; Financial Interests, Institutional, Local PI, UCLH PI for LEAP 15 and MK4280A-007 trials: MSD; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator for NOUS209-001 trial: Nouscom; Financial Interests, Institutional, Coordinating PI, UK Chief Investigator for CUPSICO trial: Roche; Financial Interests, Personal, Steering Committee Member, Steering Committee Member of CUPISCO trial: Roche; Non-Financial Interests, Member: ASCO, Association of Cancer Physicians UK. F. Rivera: Financial Interests, Personal and Institutional, Invited Speaker: MSD, Lilly, Astellas, BMS, Roche, Amgen, Merck, Servier, Novartis; Financial Interests, Personal and Institutional, Advisory Board: MSD, Lilly, Astellas, BMS, Roche, Amgen, Merck, Servier; Financial Interests, Personal and Institutional, Research Grant: MSD, AstraZeneca, BMS, Amgen, Merck, Servier, Novartis; Financial Interests, Personal and Institutional, Funding: MSD, AstraZeneca, BMS, Roche, Amgen, Merck, Servier, Novartis; Financial Interests, Personal and Institutional, Principal Investigator: MSD, AstraZeneca, Amgen, Servier. G.V. Alves: Financial Interests, Personal, Invited Speaker, Speaker: Sanofi, AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory: AstraZeneca, Merck Serono, MSD; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Institutional, Local PI: MSD, BMS, AstraZeneca, Roche, BeiGene, Janssen, Aveo, Sanofi; Financial Interests, Institutional, Other, Sub-Investigator: Zymeworks. M. Garrido: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Bayer, Pfizer, Merck, Lilly, GBT Biotoscana; Financial Interests, Personal, Advisory Board: MSD, Pfizer, MacroGenics; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Research Grant: BMS, Novartis. J. Li: Non-Financial Interests, Member: ASCO, CSCO. F.J.S.M. Cruz: Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca, MSD. L. Yin, A. Valderrama, S. Bordia: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas; Financial Interests, Personal, Invited Speaker: MSD, Lilly, Daiichi Sankyo; Financial Interests, Personal, Steering Committee Member: Amgen; Financial Interests, Institutional, Funding: MSD, Lilly; Financial Interests, Institutional, Research Grant: BMS, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Indivumed, AstraZeneca; Financial Interests, Other, Drug supply for clinical trial: Merck; Financial Interests, Institutional, Coordinating PI, Drug supply for clinical trial: MSD; Financial Interests, Institutional, Local PI, drug supply for clinical trial: Zymeworks; Financial Interests, Institutional, Local PI, drug supply for clinical trial: BeiGene; Financial Interests, Coordinating PI, Drug supply for clinical trial: Incyte. All other authors have declared no conflicts of interest.