Yoshihiko Sakata1, Shinya Sakata2, Yuko Oya3, Motohiro Tamiya4, Hidekazu Suzuki5, Ryota Shibaki6, Asuka Okada7, Hiroshi Kobe8, Hirotaka Matsumoto9, Takashi Yokoi10, Yuki Sato11, Takeshi Uenami12, Go Saito13, Yoko Tsukita14, Megumi Inaba15, Hideki Ikeda16, Daisuke Arai17, Hirotaka Maruyama18, Satoshi Hara19, Shinsuke Tsumura20, Jun Morinaga21, Takuro Sakagami2. 1. Division of Respiratory Medicine, Saiseikai Kumamoto Hospital, 5-3-1 Chikami, Minami-ku, Kumamoto, Kumamoto 861-4193, Japan. Electronic address: sakata.4415@gmail.com. 2. Department of Respiratory Medicine, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto 860-8556, Japan. 3. Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan. 4. Department of Thoracic Oncology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, Osaka 541-8567, Japan. 5. Department of Thoracic Oncology, Osaka Habikino Medical Center, 3-7-1 Habikino, Habikino, Osaka 583-8588, Japan. 6. Internal Medicine III, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-8509, Japan. 7. Department of Medical Oncology, Osaka City General Hospital, 2-13-22 Miyakojima-hondori, Miyakojima-ku, Osaka, Osaka 531-0021, Japan. 8. Department of Respiratory Medicine, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama 710-8602, Japan. 9. Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashinaniwa, Amagasaki, Hyogo, 660-8550, Japan. 10. Department of Thoracic Oncology, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya, Hyogo 663-8501, Japan. 11. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojimaminami, Chuo-ku, Kobe, Hyogo, 650-0047, Japan. 12. Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Toyonaka, Osaka, Osaka 560-8552, Japan. 13. Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba 260-8670, Japan. 14. Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 2-1 Seiryo, Aoba-ku, Sendai, Miyagi 980-8575, Japan. 15. Division of Respiratory Medicine, Kumamoto Chuo Hospital, 1-5-1 Tainoshima, Minami-ku, Kumamoto, Kumamoto 862-0965, Japan. 16. Department of Respiratory Medicine, Kimitsu Chuo Hospital, 1010 Sakurai, Kisarazu, Chiba 292-8535, Japan; Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba 260-8670, Japan. 17. Department of Internal Medicine, Saiseikai Utsunomiya Hospital, 911-1 Takebayashi, Utsunomiya, Tochigi 321-0974, Japan. 18. Department of Respiratory Medicine, Japan Organization of Occupational Health and Safety, Kumamoto Rosai Hospital, 1670 Takehara, Yatsushiro, Kumamoto 866-8533, Japan. 19. Department of Respiratory Medicine, Itami City Hospital, 1-100 Koyaike, Itami, Hyogo 664-8540, Japan. 20. Department of Respiratory Medicine, Kumamoto Regional Medical Center, 5-16-10 Honjyo, Chuo-ku, Kumamoto, Kumamoto 860-0811, Japan. 21. Department of Clinical Investigation (Biostatistics), Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto 860-8556, Japan.
Abstract
BACKGROUND: Osimertinib is the standard of care in the initial treatment for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, clinical data and reliable prognostic biomarkers are insufficient. METHODS: We performed a retrospective multicentre cohort study for 538 EGFR mutation-positive patients, who received osimertinib as the initial treatment between August 2018 and December 2019. The main outcome was progression-free survival (PFS). RESULTS: The median observation period was 14.7 months (interquartile range 11.4-20.0). The median PFS was 20.5 months (95% confidence interval [CI] 18.6-not reached). Multivariate analysis showed that sex (male) (hazard ratio [HR] 1.99, 95% CI 1.35-2.93, P = 0.001), malignant effusions (HR 1.51, 95% CI 1.11-2.04, P = 0.008), liver metastasis (HR 1.55, 95% CI 1.03-2.33, P = 0.037), advanced unresectable cases (HR 1.71, 95% CI, 1.04-2.82, P = 0.036), mutation type and programmed cell death-ligand 1 (PD-L1) expression were associated with PFS. The L858R (HR 1.55, 95% CI 1.01-2.38, P = 0.043) and uncommon mutations (HR 3.15, 95% CI 1.70-5.83, P < 0.001) were associated with PFS. PD-L1 expression of 1-49% (HR 1.66, 95% CI 1.05-2.63, P = 0.029), ≥50% (HR 2.24, 95% CI 1.17-4.30, P = 0.015) and unknown (HR 1.53, 95% CI 1.05-2.22, P = 0.026) was associated with PFS. The main reasons for treatment discontinuation among 219 patients were disease progression (44.3%), pneumonitis (25.5%) and other adverse events (16.0%). CONCLUSION: During initial treatment with osimertinib, PD-L1 expression is significantly related to PFS. Adverse events are a noteworthy reason for discontinuation.
BACKGROUND: Osimertinib is the standard of care in the initial treatment for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, clinical data and reliable prognostic biomarkers are insufficient. METHODS: We performed a retrospective multicentre cohort study for 538 EGFR mutation-positive patients, who received osimertinib as the initial treatment between August 2018 and December 2019. The main outcome was progression-free survival (PFS). RESULTS: The median observation period was 14.7 months (interquartile range 11.4-20.0). The median PFS was 20.5 months (95% confidence interval [CI] 18.6-not reached). Multivariate analysis showed that sex (male) (hazard ratio [HR] 1.99, 95% CI 1.35-2.93, P = 0.001), malignant effusions (HR 1.51, 95% CI 1.11-2.04, P = 0.008), liver metastasis (HR 1.55, 95% CI 1.03-2.33, P = 0.037), advanced unresectable cases (HR 1.71, 95% CI, 1.04-2.82, P = 0.036), mutation type and programmed cell death-ligand 1 (PD-L1) expression were associated with PFS. The L858R (HR 1.55, 95% CI 1.01-2.38, P = 0.043) and uncommon mutations (HR 3.15, 95% CI 1.70-5.83, P < 0.001) were associated with PFS. PD-L1 expression of 1-49% (HR 1.66, 95% CI 1.05-2.63, P = 0.029), ≥50% (HR 2.24, 95% CI 1.17-4.30, P = 0.015) and unknown (HR 1.53, 95% CI 1.05-2.22, P = 0.026) was associated with PFS. The main reasons for treatment discontinuation among 219 patients were disease progression (44.3%), pneumonitis (25.5%) and other adverse events (16.0%). CONCLUSION: During initial treatment with osimertinib, PD-L1 expression is significantly related to PFS. Adverse events are a noteworthy reason for discontinuation.