Takayuki Jodai1, Koichi Saruwatari2, Tokunori Ikeda3, Eiji Moriyama4, Kosuke Kashiwabara5, Naoki Shingu6, Kazuhiro Iyonaga7, Megumi Inaba8, Yusuke Ajishi9, Chiharu Honda10, Susumu Hirosako11, Hirotaka Maruyama12, Yosuke Kakiuchi13, Hirofumi Eida14, Yusuke Tomita1, Sho Saeki1, Hidenori Ichiyasu1, Takuro Sakagami1. 1. Department of Respiratory Medicine, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. 2. Department of Respiratory Medicine, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. ksaruwat@kuh.kumamoto-u.ac.jp. 3. Department of Clinical Investigation, Kumamoto University Hospital, Kumamoto, Japan. 4. Department of Medical Oncology, Miyazaki Higashi Hospital, Miyazaki, Japan. 5. Department of Respiratory Medicine, Kumamoto Regional Medical Center, Kumamoto, Japan. 6. Department of Respiratory Medicine, Saiseikai Kumamoto Hospital, Kumamoto, Japan. 7. Department of Respiratory Medicine, Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan. 8. Department of Respiratory Medicine, Kumamoto Chuo Hospital, Kumamoto, Japan. 9. Department of Respiratory Medicine, Miyazaki Prefectural Nobeoka Hospital, Nobeoka, Japan. 10. Department of Respiratory Medicine, Tamana Central Hospital, Tamana, Japan. 11. Department of Respiratory Medicine, Omuta Tenryo Hospital, Omuta, Japan. 12. Department of Respiratory Medicine, Japan Organization of Occupational Health and Safety, Kumamoto Rosai Hospital, Yatushiro, Japan. 13. Department of Respiratory Medicine, National Hospital Organization Kumamoto Saishun Medical Center, Koshi, Japan. 14. Department of Respiratory Medicine, Minamata City General Hospital and Medical Center, Minamata, Japan.
Abstract
BACKGROUND: Anti-programmed cell death protein-1/ligand-1 (anti-PD-1/PD-L1) therapy is promising for patients with non-small-cell lung cancer (NSCLC); however, clinical trials have focused on patients with a performance status (PS) 0 or 1. This study aimed to evaluate the clinical outcomes and correlation between PD-L1 expression status and tumor response to anti-PD-1/PD-L1 therapy among NSCLC patients with poor PS (i.e., PS ≥ 2). METHODS: In total, 130 patients with NSCLC and PS ≥ 2 treated with anti-PD-1/PD-L1 monotherapy at 12 institutions between January 2016 and August 2019 were retrospectively reviewed. PD-L1 expression status was divided into four groups: < 1%, 1-49%, ≥ 50%, and unknown. RESULTS: The objective response rate and PS improvement rate were 23 and 21% and were higher in the PD-L1 ≥ 50% group than in other groups (P < 0.01). Median progression-free survival (PFS) was 62 days and was longer in the PD-L1 ≥ 50% group than in other groups (P = 0.03). Multivariate analyses revealed that PD-L1 expression is significantly associated with prolonged PFS (PD-L1 < 1%; reference; 1-49%, hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.04-0.99, P = 0.05; ≥ 50%, HR 0.12, 95% CI 0.02-0.71, P = 0.02; unknown, HR 0.30, 95% CI 0.08-1.22, P = 0.09). CONCLUSIONS: NSCLC patients with poor PS and PD-L1 ≥ 50% are expected to benefit from anti-PD-1/PD-L1 therapy, despite a modest overall response among NSCLC patients with poor PS. Accordingly, PD-L1 expression provides useful information regarding decision-making for anti-PD-1/PD-L1 therapy even in these populations.
BACKGROUND: Anti-programmed cell death protein-1/ligand-1 (anti-PD-1/PD-L1) therapy is promising for patients with non-small-cell lung cancer (NSCLC); however, clinical trials have focused on patients with a performance status (PS) 0 or 1. This study aimed to evaluate the clinical outcomes and correlation between PD-L1 expression status and tumor response to anti-PD-1/PD-L1 therapy among NSCLCpatients with poor PS (i.e., PS ≥ 2). METHODS: In total, 130 patients with NSCLC and PS ≥ 2 treated with anti-PD-1/PD-L1 monotherapy at 12 institutions between January 2016 and August 2019 were retrospectively reviewed. PD-L1 expression status was divided into four groups: < 1%, 1-49%, ≥ 50%, and unknown. RESULTS: The objective response rate and PS improvement rate were 23 and 21% and were higher in the PD-L1 ≥ 50% group than in other groups (P < 0.01). Median progression-free survival (PFS) was 62 days and was longer in the PD-L1 ≥ 50% group than in other groups (P = 0.03). Multivariate analyses revealed that PD-L1 expression is significantly associated with prolonged PFS (PD-L1 < 1%; reference; 1-49%, hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.04-0.99, P = 0.05; ≥ 50%, HR 0.12, 95% CI 0.02-0.71, P = 0.02; unknown, HR 0.30, 95% CI 0.08-1.22, P = 0.09). CONCLUSIONS:NSCLCpatients with poor PS and PD-L1 ≥ 50% are expected to benefit from anti-PD-1/PD-L1 therapy, despite a modest overall response among NSCLCpatients with poor PS. Accordingly, PD-L1 expression provides useful information regarding decision-making for anti-PD-1/PD-L1 therapy even in these populations.
Authors: Edward B Garon; Naiyer A Rizvi; Rina Hui; Natasha Leighl; Ani S Balmanoukian; Joseph Paul Eder; Amita Patnaik; Charu Aggarwal; Matthew Gubens; Leora Horn; Enric Carcereny; Myung-Ju Ahn; Enriqueta Felip; Jong-Seok Lee; Matthew D Hellmann; Omid Hamid; Jonathan W Goldman; Jean-Charles Soria; Marisa Dolled-Filhart; Ruth Z Rutledge; Jin Zhang; Jared K Lunceford; Reshma Rangwala; Gregory M Lubiniecki; Charlotte Roach; Kenneth Emancipator; Leena Gandhi Journal: N Engl J Med Date: 2015-04-19 Impact factor: 91.245
Authors: Julie Brahmer; Karen L Reckamp; Paul Baas; Lucio Crinò; Wilfried E E Eberhardt; Elena Poddubskaya; Scott Antonia; Adam Pluzanski; Everett E Vokes; Esther Holgado; David Waterhouse; Neal Ready; Justin Gainor; Osvaldo Arén Frontera; Libor Havel; Martin Steins; Marina C Garassino; Joachim G Aerts; Manuel Domine; Luis Paz-Ares; Martin Reck; Christine Baudelet; Christopher T Harbison; Brian Lestini; David R Spigel Journal: N Engl J Med Date: 2015-05-31 Impact factor: 91.245
Authors: Martin Reck; Delvys Rodríguez-Abreu; Andrew G Robinson; Rina Hui; Tibor Csőszi; Andrea Fülöp; Maya Gottfried; Nir Peled; Ali Tafreshi; Sinead Cuffe; Mary O'Brien; Suman Rao; Katsuyuki Hotta; Melanie A Leiby; Gregory M Lubiniecki; Yue Shentu; Reshma Rangwala; Julie R Brahmer Journal: N Engl J Med Date: 2016-10-08 Impact factor: 91.245
Authors: C Gridelli; A Ardizzoni; T Le Chevalier; C Manegold; F Perrone; N Thatcher; N van Zandwijk; M Di Maio; O Martelli; F De Marinis Journal: Ann Oncol Date: 2004-03 Impact factor: 32.976
Authors: Hossein Borghaei; Luis Paz-Ares; Leora Horn; David R Spigel; Martin Steins; Neal E Ready; Laura Q Chow; Everett E Vokes; Enriqueta Felip; Esther Holgado; Fabrice Barlesi; Martin Kohlhäufl; Oscar Arrieta; Marco Angelo Burgio; Jérôme Fayette; Hervé Lena; Elena Poddubskaya; David E Gerber; Scott N Gettinger; Charles M Rudin; Naiyer Rizvi; Lucio Crinò; George R Blumenschein; Scott J Antonia; Cécile Dorange; Christopher T Harbison; Friedrich Graf Finckenstein; Julie R Brahmer Journal: N Engl J Med Date: 2015-09-27 Impact factor: 91.245