Review

Predictive value of PD-L1 and other clinical factors for chemoimmunotherapy in advanced non-small-cell lung cancer

Cancer Care Centre, St George Hospital, Kogarah, Sydney, New South Wales 2217, Australia

^‡Authors contributed equally

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Yanni Loh^‡

Cancer Care Centre, St George Hospital, Kogarah, Sydney, New South Wales 2217, Australia

^‡Authors contributed equally

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Joanna Lee

Cancer Care Centre, St George Hospital, Kogarah, Sydney, New South Wales 2217, Australia

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Wendy Cooper

Tissue Pathology & Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales 2050, Australia

Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia

School of Medicine, Western Sydney University, Penrith, Sydney, New South Wales 2751, Australia

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Ian Marschner

National Health & Medical Research Council Clinical Trials Centre, The University of Sydney, Camperdown, Sydney, New South Wales 1450, Australia

Department of Statistics, Macquarie University, North Ryde, Sydney, New South Wales 2109, Australia

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Craig R Lewis

Prince of Wales Hospital Clinical School, University of NSW, Randwick, Sydney, New South Wales 2031, Australia

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Michael Millward

School of Medicine, University of Western Australia, Perth, Western Australia 6009, Australia

Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia 6010, Australia

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Sally Lord

National Health & Medical Research Council Clinical Trials Centre, The University of Sydney, Camperdown, Sydney, New South Wales 1450, Australia

School of Medicine, University of Notre Dame, Darlinghurst, Sydney, New South Wales 2010, Australia

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Richard J Gralla

Albert Einstein College of Medicine, Jacobi Medical Center, The Bronx, NY 10461, USA

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James C-H Yang

Graduate Institute of Oncology, National Taiwan University & Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan 10002, Taiwan

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Tony Mok

Department of Clinical Oncology, Hong Kong Cancer Institute, Chinese University of Hong Kong, Shatin NT, PR China

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Chee K Lee

*Author for correspondence: Tel.: +61295625365; Fax: +61295651863;

E-mail Address: chee.lee@ctc.usyd.edu.au

Cancer Care Centre, St George Hospital, Kogarah, Sydney, New South Wales 2217, Australia

National Health & Medical Research Council Clinical Trials Centre, The University of Sydney, Camperdown, Sydney, New South Wales 1450, Australia

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Published Online:25 Jun 2019https://doi.org/10.2217/fon-2019-0105

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Abstract

We investigate if PD-L1 expression and other clinical characteristics predict chemoimmunotherapy (CIT) benefits versus chemotherapy in advanced non-small-cell lung cancer. We performed a meta-analysis of randomized controlled trials of CIT versus chemotherapy identified through electronic searches. In seven randomized controlled trials (n = 4170), CIT prolonged progression-free survival over chemotherapy (hazard ratio [HR]: 0.62; 95% CI: 0.58–0.67; p < 0.00001). The treatment benefits differed between PD-L1-high (HR: 0.41; 95% CI: 0.34–0.49) and PD-L1 low (HR: 0.63; 95% CI: 0.55–0.72; interaction-p = 0.00002) and PD-L1-high and PD-L1-negative (HR: 0.72; 95% CI: 0.65–0.80; interaction-p < 0.00001). Similar benefits were observed regardless of gender, EGFR/ALK status and histological subtype. PD-L1 status is predictive of CIT benefit and may assist patient selection and design of future trials.

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Papers of special note have been highlighted as: • of interest

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Vol. 15, No. 20

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Received 23 February 2019

Accepted 23 April 2019

Published online 25 June 2019

Published in print July 2019

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fon-2019-0105

Acknowledgments

The authors acknowledge the editorial support provided by Sherilyn Goldstone (NHMRC Clinical Trials Centre).

Author’s contributions

CK Lee contributed to the conception and design; R Woodford, Y Loh, J Lee, CK Lee conceived the data acquisition, data analysis and original manuscript drafting. All the authors reviewed and approved the final version of manuscript.

Financial & competing interests disclosure

There is no specific funding for this research. M Millard reports being advisory board member for Bristol-Myers Squibb, Astrazeneca, Roche, Merck Sharp & Dohme. JCH Yang reports receiving honoraria and advisory fees from Eli Lilly, Boehringer Ingelheim, Roche/Genentech/Chugai, Merck Sharp & Dohme, Pfizer, Novartis, Bristol-Myers Squibb, Ono Pharmaceutical, Takeda, and AstraZeneca, and advisory fees from Bayer, Astellas, Merck Serono, Celgene, Merrimack, Yuhan Pharmaceuticals, Daiichi Sankyo, and Jiangsu Hansoh Pharmaceutical. T Mok reports receiving fees for serving on advisory boards from AstraZeneca, Roche/Genentech, Eli Lilly and Company, Merck Serono, ACEA Biosciences, Bristol-Myers Squibb, AVEO-Biodesix, Pfizer, Boehringer Ingelheim, Novartis Pharmaceuticals, GlaxoSmithKline, Clovis Oncology, Amgen, Janssen, BioMarin Pharmaceuticals, SFJ Pharmaceuticals, Merck Sharp & Dohme, Vertex Pharmaceuticals, Oncogenex, and Celgene, consulting fees from geneDecode, lecture fees from AstraZeneca, Roche/Genentech, Eli Lilly and Company, Merck Serono, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Novartis Pharmaceuticals, GlaxoSmithKline, Clovis Oncology, Amgen, Merck Sharp & Dohme, and Prime Oncology, and holding stock in Sanomics. CK Lee reports receiving fees for serving on advisory boards from AstraZeneca, Roche, Novartis, Pfizer and Takeda; receiving travel support from AstraZeneca and CK Lee’s institution receiving research grant from Astrazeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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