Health-related quality of life associated with trifluridine/tipiracil in heavily pretreated metastatic gastric cancer: results from TAGS

Abstract

Background: In TAGS, an international, double-blind, phase 3 trial, trifluridine/tipiracil significantly improved overall survival and progression-free survival compared with placebo in heavily pretreated metastatic gastric cancer patients. This paper reports pre-specified quality of life (QoL) outcomes for TAGS.

Methods: Patients were randomized 2:1 to trifluridine/tipiracil (35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle) plus best supportive care (BSC) or placebo plus BSC. QoL was evaluated at baseline and at each treatment cycle, using the EORTC QLQ-C30 and EORTC QLQ-STO22 questionnaires; results were considered valid for analysis only if ≥ 10% of patients completed the questionnaires. Key QoL outcomes were mean changes from baseline and time to deterioration in QoL. A post hoc analysis assessed the association between QoL and time to deterioration of Eastern Cooperative Oncology Group performance score (ECOG PS) to ≥ 2.

Results: Of 507 randomized patients, 496 had baseline QoL data available. The analysis cut-off was 6 cycles for trifluridine/tipiracil and 3 cycles for placebo. In both treatment groups, there were no clinically significant deteriorations in the mean QLQ-C30 Global Health Status (GHS) score, or in most subscale scores. In a sensitivity analysis including death and disease progression as events, there was a trend towards trifluridine/tipiracil reducing the risk of deterioration of QoL scores compared with placebo. Deterioration in the GHS score was associated with deterioration in ECOG PS.

Conclusion: QoL was maintained in TAGS, and there was a trend towards trifluridine/tipiracil reducing the risk of QoL deterioration compared with placebo. Trial registration ClinicalTrials.gov number: NCT02500043.

Keywords: Gastric cancer; Health-related quality of life; Phase 3; Trifluridine/tipiracil.

Conflict of interest statement

Josep Tabernero reports personal fees from Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F. Hoffmann-La Roche Ltd, Sanofi, SeaGen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. Maria Alsina reports personal financial interest in form of scientific consultancy for BMS, Lilly, MSD and Servier Honorarium for speaking issues from Amgen, BMS, Lilly, MSD, Roche and Servier Travel expenses partially covered by Amgen, Lilly and Roche. Kohei Shitara reports grants and personal fees from Astellas Pharma, Lilly, Ono Pharmaceutical, and MSD; personal fees from Bristol-Myers Squibb, Takeda, Pfizer, Novartis, Abbvie, and Yakult; grants from Dainippon Sumitomo Pharma, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharma, and Medi Science. Toshihiko Doi reports grants from Lilly, Kyowa Hakko Kirin, MSD, Daiichi Sankyo, Amgen, Sumitomo Dainippon, Taiho, Novartis, Merck Serono, Astellas, Janssen, Boehringer Ingelheim, Takeda, Pfizer, Chugai Pharma, Celegene, Bristol-Myers Squibb, Abbvie, Quintiles, Bayer, and Eisai. Hendrik-Tobias Arkenau reports personal fees from Roche, Bicycle therapeutics, BioNTech, BeiGene. Michele Ghidini reports personal fees from Lilly, Servier for advisory boards. Catia Faustino reports personal fees from Servier, Merck Serono, Ipsen, Novartis, and Astellas. Kazuhiro Nishikawa reports personal fees from Chugai Pharma, Taiho Pharmaceutical, Yakult Honsha, Bristol-Myers Squibb Japan, EA Pharma, Lilly, and Ono Pharmaceutical; grants from Taiho Pharmaceutical, and Ono Pharmaceutical. Şuayib Yalçın reports honoraria from Roche, Pfizer, Amgen, Merck Serono, and Lilly. Eric Van Cutsem has received research funding from Amgen, Bayer, Boehringer Ingelheim, Celgene, Ipsen, Lilly, Merck, Merck KgA, Novartis, Roche, Sanofi, and Servier. Javier Sabater, Donia Skanji, Catherine Leger and Nadia Amellal are employees of Servier. David Ilson has served as a consultant/advisor for Amgen, Lilly, Roche, Genentech, Astra-Zeneca, Taiho, and Pieris and has received research funding from Bristol-Myers Squibb, Bayer, Taiho, and Amgen. Mikhail Dvorkin, Wasat Mansoor, Aliaksandr Prokharau, Vera Gorbunova, Edvard Zhavrid, and Takayuki Ando have no conflicts of interest to disclose.

Figures

Fig. 1

Change from baseline across treatment cycles* in the EORTC QLQ-C30 GHS score EORTC, European Organization for Research and Treatment of Cancer; GHS, global health status; QLQ-C30, Quality of Life Questionnaire-Core 30. *Results were considered valid for analysis only if ≥ 10% of the original patient population completed the questionnaires; this corresponded to 3 cycles of treatment with placebo and 6 cycles for trifluridine/tipiracil. A high score represents a high quality of life. A mean change from baseline of ≥ 10 points is considered clinically relevant

Fig. 2

Change from baseline to treatment cycle 3 in the EORTC (a) QLQ-C30 function scores (b) QLQ-C30 symptom scores and (c) QLQ-STO22 subscores. EORTC, European Organization for Research and Treatment of Cancer; GHS, Global Health Status; QLQ-C30, Quality of Life Questionnaire-Core 30; QLQ-STO22, Quality of Life Questionnaire-Gastric Cancer Module

Fig. 3

Time to deterioration in EORTC QoL scores by ≥ 10 points: sensitivity analyses including (a) death as an event and (b) disease progression and death as events. CI, confidence interval; EORTC, European Organization for Research and Treatment of Cancer; GHS, global health status; HR, hazard ratio; ITT, intention to treat; QLQ-C30, Quality of Life Questionnaire-Core 30; QLQ-STO22, Quality of Life Questionnaire-Gastric Cancer Module; QoL, quality of life. *Stratification factors were baseline Eastern Cooperative Oncology Group performance status (ECOG PS 0 vs 1) status, prior treatment with ramucirumab and region (Japan vs rest of World)

Fig. 4

Association between time to deterioration of ECOG PS to ≥ 2 and time to deterioration of QoL score by ≥ 10 points. CI, confidence interval; EORTC, European Organization for Research and Treatment of Cancer; GHS, global health status; HR, hazard ratio; ITT, intention to treat; QLQ-C30, Quality of Life Questionnaire-Core 30; QLQ-STO22, Quality of Life Questionnaire-Gastric Cancer Module; QoL, quality of life