Tislelizumab (TIS) plus chemotherapy (chemo) vs placebo (PBO) plus chemo as first-line treatmentof advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC): Health-related
quality of life outcomes in the RATIONALE-305 study
Authors: Ken Kato,1* Marcia Cruz Correa,2 Rui-Hua Xu,3 Markus Moehler,4 Do-Youn Oh,5 DavidSpigel,6 Hendrik-Tobias Arkenau,7 Josep Tabernero,8 Anastasia V. Zimina,9 Yuxian Bai,10 Jianhua Shi,11Keun-Wook Lee,12 Hidekazu Hirano,5 Lucjan Wyrwicz,13 Roberto Pazo Cid,14 Hui Xu,15 Tao Sheng,16Gisoo Barnes16
Affiliations: 1National Cancer Center Hospital, Department of Gastrointestinal Medical Oncology,Tokyo, Japan; 2University of Puerto Rico, School of Medicine, San Juan, Puerto Rico; 3UniversityCancer Center State Key Laboratory of Oncology in South China, Collaborative Innovation Center ofCancer Medicine, Department of Medical Oncology, Guangzhou, China; 4Johannes-Gutenberg
University Clinic, Department of Internal Medicine I, Mainz, Germany; 5Seoul National University
Hospital Cancer Research Institute, Seoul National University College of Medicine, Department ofInternal Medicine, Seoul, South Korea; 6Sarah Cannon Research Institute, Nashville, TN, USA; 7SarahCannon Research, London, UK; 8Vall d’Hebron University Hospital, Department of Medical Oncology,Barcelona, Spain; 9BIH of Omsk Region, Clinical Oncology Dispensary, Omsk Oblast, Russia; 10Harbin
Medical University Cancer Hospital, Department of Gastrointestinal Oncology, Harbin, China; 11Linyi
Cancer Hospital, Department II of Medical Oncology, Linyi, China; 12Seoul National University Collegeof Medicine, Seoul National University Bundang Hospital, Department of Medical Oncology (InternalMedicine), Seongnam, South Korea; 13Maria Sklodowska-Curie National Cancer Research Institute,
Department of Oncology and Radiotherapy, Warsaw, Poland; 14Hospital Universitario Miguel Servet,
Department of Medical Oncology, Zaragoza, Spain; 15BeiGene (Beijing) Co., Ltd., Beijing, China;
16
BeiGene USA, Inc., San Mateo, CA, USA
ABSTRACTIntroduction: RATIONALE-305 (NCT03777657) demonstrated statistically significant and clinicallymeaningful improvements in overall survival (OS) with TIS+chemo (n=501) over PBO+chemo (n=496)
as first-line treatment in patients with advanced GC/GEJC. We examined health-related quality of life(HRQoL) outcomes in the RATIONALE-305 study at the final analysis.
Methods: Adults with previously untreated, unresectable, or metastatic GC/GEJC were randomized(1:1) to TIS 200 mg or PBO IV once every 3 weeks plus investigator-choice of chemo. HRQoL wasassessed using EORTC QLQ-C30 and the QLQ-STO22. A mixed model for repeated measures ofpatient-reported outcomes (PRO) endpoints at clinical Cycles 4 and 6 was performed. Time todeterioration was examined.
Results: TIS+chemo had improved outcomes (least-square mean change from baseline) vsPBO+chemo (Table) as indicated by the estimated mean treatment difference at Cycle 6 for QLQ-C30
GHS/QoL (2.52 [95% CI, 0.29-4.74]), physical functioning (2.46 [0.49-4.43]), fatigue (-3.01 [-5.78 to 0.24]), and STO22 index score (-1.62 [-3.12 to -0.12]), and maintaining upper gastrointestinal
symptoms (-1.74 [95% CI, -3.55 to 0.06)] and pain (-1.88 [-4.03 to 0.27]). Patients receiving
TIS+chemo had lower risk of deterioration of GHS/QoL (HR, 0.77 [95% CI, 0.60-0.98]), physicalfunctioning (0.72 [0.57-0.92]), STO22 index score (0.64 [0.45-0.92]), pain/discomfort (0.74 [0.580.96]), and upper gastrointestinal symptoms (0.73 [0.56-0.95]).
Conclusions: Patients treated with TIS+chemo had better HRQoL outcomes vs those treated withPBO+chemo, particularly for GHS/QoL, physical functioning, fatigue, GC/GEJC symptoms,pain/discomfort, and upper GI symptoms. These results, along with prolonging of OS and other
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secondary efficacy endpoints, as well as a tolerable safety profile, support the benefit of TIS+chemo
as a potential first-line treatment option for GC/GEJC.
Cycle 4
TIS+chemo
n=501
Mean (95% CI)

Cycle 4
PBO+chemo n=496
Mean (95% CI)

Cycle 6
TIS+chemo
n=501
Mean (95% CI)

Cycle 6
PBO+chemo
n=496
Mean (95% CI)

1.35 (-0.24, 2.94)-0.45 (-2.04, 1.13)

0.93 (-0.71, 2.57)-1.58 (-3.24, 0.07)

Physical functioning-2.47 (-3.77, -1.18)-3.92 (-5.21, -2.62)-2.76 (-4.22, -1.30)-5.22 (-6.69, -3.75)

Fatigue

1.75 (-0.09, 3.60)

3.07 (1.23, 4.91)

1.71 (-0.32, 3.75)

4.73 (2.68, 6.77)

QLQ- STO22
Index score-1.71 (-2.77, -0.66)-0.61 (-1.66, 0.45)-1.84 (-2.95, -0.74)-0.22 (-1.34, 0.89)

Dysphagia-2.78 (-3.99, -1.57)-1.27 (-2.48, -0.06)-2.79 (-3.93, -1.64)-2.01 (-3.17, -0.86)

Pain/discomfort-6.88 (-8.39, -5.36)-4.64 (-6.16, -3.13)-5.97 (-7.56, -4.38)-4.09 (-5.69, -2.49)

Dietary restrictions-0.31 (-1.75, 1.12)

0.61 (-0.82, 2.05)-0.25 (-1.79, 1.30)

1.08 (-0.48, 2.63)

Upper
gastrointestinal
symptoms-3.14 (-4.40, -1.87)-1.54 (-2.80, -0.28)-3.24 (-4.58, -1.90)-1.49 (-2.84, -0.14)

QLQ-C30

GHS/QoL

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