Examining the Impact of Tislelizumab Added to Chemotherapy on Health-Related Quality-of-Life Outcomes in Previously Untreated Patients With Nonsquamous Non-Small Cell Lung Cancer

Shun Lu, Yan Yu, Gisoo Barnes, Xiusong Qiu, Yuanyuan Bao, Boxiong Tang, Shun Lu, Yan Yu, Gisoo Barnes, Xiusong Qiu, Yuanyuan Bao, Boxiong Tang

Abstract

Purpose: This study assessed the effects of tislelizumab, a programmed cell death protein 1 inhibitor, in combination with chemotherapy versus chemotherapy alone as first-line treatment on health-related quality of life (HRQoL) in patients with advanced nonsquamous non-small cell lung cancer (nSQ-NSCLC).

Methods: Patients in this randomized, open-label, multicenter phase III study RATIONALE 304 (NCT03663205) with histologically confirmed stage IIIB/IV nSQ-NSCLC were randomized 2:1 to tislelizumab plus platinum-pemetrexed (arm T + PP) or platinum-pemetrexed alone (arm PP). Health-related QoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer. Key patient-reported outcome endpoints include mean score change from baseline at weeks 12 (during chemotherapy) and 18 (following chemotherapy) in the 30-item Quality of Life Questionnaire Core's global health status/quality of life (GHS/QoL) and time to deterioration in GHS/QoL.

Results: Three hundred thirty-two patients received at least 1 dose of study drug and completed at least 1 HRQoL assessment. Global health status/QoL score improved in arm T + PP at week 18 (between-group least square mean difference, 5.7; 95% confidence interval [CI], 1.0-10.5; P = 0.018). Patients in arm T + PP experienced greater reduction in coughing (-5.9; 95% CI, -11.6 to -0.1; P = 0.044), dyspnea (-3.8; 95% CI, -7.8 to 0.1; P = 0.059), chest pain (-6.2; 95% CI, -10.8 to -1.6; P = 0.008), and peripheral neuropathy (-2.6; 95% CI, -5.5 to 0.2; P = 0.066). Median time to deterioration in GHS/QoL was not achieved for either arm.

Discussion: The addition of tislelizumab to platinum-based chemotherapy was associated with improvements in nSQ-NSCLC patients' HRQoL as well as the important disease-specific symptoms of coughing, chest pain, and dyspnea.ClinicalTrials.gov Identifier: NCT03663205.

Conflict of interest statement

Conflicts of Interest and Source of Funding: S.L. reports research support received from AstraZeneca, Hutchison, BMS, Heng Rui, and Roche; speaker fees received from AstraZeneca, Roche, BeiGene Ltd., and Hansoh; and advisor/consultant fees received from AstraZeneca, Boehringer Ingelheim, Hutchison MediPharma, Simcere, ZaiLab, GenomiCare, and Roche. G.B., X.Q., Y.B., and B.T. are employees of and own stock in BeiGene Ltd. For Y.Y., none were declared. This study was sponsored by BeiGene, Ltd. Support for the development of this manuscript was provided by BeiGene, Ltd.

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Figures

FIGURE 1
FIGURE 1
CONSORT diagram. Disposition of patients in the study. CP indicates clinical progression; ITT, intent-to-treat; RP, radiographic progression. aOne patient randomized to combination therapy was not treated because inclusion criteria were not met. bOne patient randomized to pemetrexed-platinum therapy was not treated owning to withdrawal of consent.
FIGURE 2
FIGURE 2
Mean change from baseline in QLQ-C30 GHS/QoL scale scores.

References

    1. Bray F Ferlay J Soerjomataram I, et al. . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.
    1. Chen W Zheng R Baade PD, et al. . Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–132.
    1. Zhi XY Wu YL Bu H, et al. . Chinese guidelines on the diagnosis and treatment of primary lung cancer (2011). J Thorac Dis. 2012;4:88–101.
    1. Desai J Deva S Lee JS, et al. . Phase IA/IB study of single-agent tislelizumab, an investigational anti–PD-1 antibody, in solid tumors. J Immunother Cancer. 2020;8:e000453.
    1. Iyer S Roughley A Rider A, et al. . The symptom burden of non–small cell lung cancer in the USA: a real-world cross-sectional study. Support Care Cancer. 2014;22:181–187.
    1. Iyer S, Taylor-Stokes G, Roughley A. Symptom burden and quality of life in advanced non–small cell lung cancer patients in France and Germany. Lung Cancer. 2013;81:288–293.
    1. Dai YL Yang CT Chen KH, et al. . Changes in and determinants of quality of life in patients with advanced non–small-cell lung cancer undergoing initial chemotherapy. J Nurs Res. 2017;25:203–215.
    1. Lee LJ Chung CW Chang YY, et al. . Comparison of the quality of life between patients with non–small-cell lung cancer and healthy controls. Qual Life Res. 2011;20:415–423.
    1. Gandhi L Rodríguez-Abreu D Gadgeel S, et al. . Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med. 2018;378:2078–2092.
    1. West H McCleod M Hussein M, et al. . Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non–small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20:924–937.
    1. Jiang T Zhou C Hu J, et al. . Combination immune checkpoint inhibitors with platinum-based chemotherapy in advanced non–small cell lung cancer: what's known and what's next. Transl Lung Cancer Res. 2019;8:S447–S450.
    1. Garassino MC Gadgeel S Esteban E, et al. . Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non–small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21:387–397.
    1. Reck M Schenker M Lee KH, et al. . Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non–small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial. Eur J Cancer. 2019;116:137–147.
    1. Brahmer JR Rodríguez-Abreu D Robinson AG, et al. . Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1–positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017;18:1600–1609.
    1. Zhang T Song X Xu L, et al. . The binding of an anti–PD-1 antibody to FcγRΙ has a profound impact on its biological functions. Cancer Immunol Immunother. 2018;67:1079–1090.
    1. Dahan R Sega E Engelhardt J, et al. . FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell. 2015;28:285–295.
    1. Wang J Lu S Yu X, et al. . Phase 3 Study of Tislelizumab Plus Chemotherapy Versus Chemotherapy Alone as First-Line Treatment for Advanced Squamous Non–Small Cell Lung Cancer. Chicago, IL: American Society of Clinical Oncology; 2020.
    1. Shen L Guo J Zhang Q, et al. . Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1/2 study. J Immunother Cancer. 2020;8:e000437.
    1. Lu S Wang J Yu Y, et al. . Tislelizumab plus chemotherapy as first-line treatment for locally advanced or metastatic nonsquamous NSCLC (RATIONALE 304): a randomized phase 3 trial. J Thorac Oncol. 2021;16:1512–1522.
    1. Aaronson NK Ahmedzai S Bergman B, et al. . The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–376.
    1. Bergman B Aaronson NK Ahmedzai S, et al. . The EORTC QLQ-LC13: a modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC Study Group on Quality of Life. Eur J Cancer. 1994;30a:635–642.
    1. Kemmler G Holzner B Kopp M, et al. . Comparison of two quality-of-life instruments for cancer patients: the Functional Assessment of Cancer Therapy—General and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30. J Clin Oncol. 1999;17:2932–2940.
    1. Koller M Hjermstad MJ Tomaszewski KA, et al. . An international study to revise the EORTC questionnaire for assessing quality of life in lung cancer patients. Ann Oncol. 2017;28:2874–2881.

Source: PubMed

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