Yuji Minegishi1, Ou Yamaguchi2, Shunichi Sugawara3, Shoichi Kuyama4, Satoshi Watanabe5, Kazuhiro Usui6, Masahide Mori7, Osamu Hataji8, Toshihiro Nukiwa9, Satoshi Morita10, Kunihiko Kobayashi2, Akihiko Gemma11. 1. Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 113-8603 1-1-5 Sendagi Bunkyo-Ku, Tokyo, Japan. yminegis@nms.ac.jp. 2. Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397 Yamane, Hidaka City, Saitama, 350-1298, Japan. 3. Department of Pulmonary Medicine, Sendai Kousei Hospital, 4-15 Hirose-machi, Aoba-ku, Sendai, 980-0873, Japan. 4. Department of Respiratory Medicine, National Hospital Organization, Iwakuni Clinical Center, 1-1-1 Atago Cyo, Iwakuni City, Yamaguchi Prefecture, 740-8510, Japan. 5. Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuouku, Niigata, 951-8510, Japan. 6. Division of Respirology, NTT Medical Center Tokyo, 5-9-22 Higashigotanda Shinagawa, Tokyo, Japan. 7. Department of Thoracic Oncology, National Hospital Organization Osaka Toneyama Medical Center, 5-1-1 Toneyama, Toyonaka City, Osaka, 560-8552, Japan. 8. Respiratory Center, Matsusaka Municipal Hospital, 1550 Tonomachi, Matsusaka City, Mie, 515-8544, Japan. 9. Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan. 10. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. 11. Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 113-8603 1-1-5 Sendagi Bunkyo-Ku, Tokyo, Japan.
Abstract
BACKGROUND: Lung cancer is most common among older individuals. However, polypharmacy and comorbidities, which are also more common in older individuals, can limit treatment options. Previous studies suggest that afatinib can be used safely and effectively in elderly patients. This study investigated the anti-tumour activity and safety profile of first-line afatinib in previously-untreated elderly Japanese patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). METHODS: This was a single-arm, open-label, phase II study, performed in multiple centres in Japan. Previously untreated patients, aged ≥75 years, with EGFR mutation-positive (Del19 or L858R) advanced NSCLC were treated with afatinib 40 mg until disease progression or unacceptable toxicity. Adverse events (AEs) were managed with protocol-defined dose adjustments. The primary endpoint was objective response rate (ORR) by central review. RESULTS: In total, 38 patients received at least one dose of afatinib, and 37 were evaluable for response. Median age was 77.5 years (range 75-91), all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and 60.5% had Del19-positive disease. Median follow-up was 838 days. ORR was 75.7% (2 complete responses and 26 partial responses). Median progression-free survival was 14.2 months (95% confidence interval [CI], 9.5-19.0). Median overall survival (OS) was 35.2 months (95% CI, 35.2-not reached); the 2-year OS rate was 78.3%. The most common grade 3/4 treatment-related AEs (TRAEs) were diarrhoea (28.9%), paronychia (23.7%), and rash/acne (15.8%). Dose reductions due to TRAEs were reported in 78.9% of patients, and eight (21.1%) patients discontinued afatinib due to TRAEs. No treatment-related deaths were reported. CONCLUSION: Although dose adjustments were relatively common in this small group of Japanese patients aged ≥75 years with EGFR mutation-positive NSCLC, discontinuation occurred much less frequently, and most patients were able to stay on treatment for well over a year. Further, afatinib was associated with high response rates and prolonged PFS and OS. TRIAL REGISTRATION: The trial is registered with Japan Registry of Clinical Trials (JRCT) as trial number 031180136 (date of initial registration: 19 February 2019), and the University Hospital Network (UMIN) as trial number 000017877 (date of initial registration: 11 June 2015).
BACKGROUND:Lung cancer is most common among older individuals. However, polypharmacy and comorbidities, which are also more common in older individuals, can limit treatment options. Previous studies suggest that afatinib can be used safely and effectively in elderly patients. This study investigated the anti-tumour activity and safety profile of first-line afatinib in previously-untreated elderly Japanese patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). METHODS: This was a single-arm, open-label, phase II study, performed in multiple centres in Japan. Previously untreated patients, aged ≥75 years, with EGFR mutation-positive (Del19 or L858R) advanced NSCLC were treated with afatinib 40 mg until disease progression or unacceptable toxicity. Adverse events (AEs) were managed with protocol-defined dose adjustments. The primary endpoint was objective response rate (ORR) by central review. RESULTS: In total, 38 patients received at least one dose of afatinib, and 37 were evaluable for response. Median age was 77.5 years (range 75-91), all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and 60.5% had Del19-positive disease. Median follow-up was 838 days. ORR was 75.7% (2 complete responses and 26 partial responses). Median progression-free survival was 14.2 months (95% confidence interval [CI], 9.5-19.0). Median overall survival (OS) was 35.2 months (95% CI, 35.2-not reached); the 2-year OS rate was 78.3%. The most common grade 3/4 treatment-related AEs (TRAEs) were diarrhoea (28.9%), paronychia (23.7%), and rash/acne (15.8%). Dose reductions due to TRAEs were reported in 78.9% of patients, and eight (21.1%) patients discontinued afatinib due to TRAEs. No treatment-related deaths were reported. CONCLUSION: Although dose adjustments were relatively common in this small group of Japanese patients aged ≥75 years with EGFR mutation-positive NSCLC, discontinuation occurred much less frequently, and most patients were able to stay on treatment for well over a year. Further, afatinib was associated with high response rates and prolonged PFS and OS. TRIAL REGISTRATION: The trial is registered with Japan Registry of Clinical Trials (JRCT) as trial number 031180136 (date of initial registration: 19 February 2019), and the University Hospital Network (UMIN) as trial number 000017877 (date of initial registration: 11 June 2015).
Authors: J C-H Yang; L V Sequist; C Zhou; M Schuler; S L Geater; T Mok; C-P Hu; N Yamamoto; J Feng; K O'Byrne; S Lu; V Hirsh; Y Huang; M Sebastian; I Okamoto; N Dickgreber; R Shah; A Märten; D Massey; S Wind; Y-L Wu Journal: Ann Oncol Date: 2016-09-06 Impact factor: 32.976
Authors: Keunchil Park; Eng-Huat Tan; Ken O'Byrne; Li Zhang; Michael Boyer; Tony Mok; Vera Hirsh; James Chih-Hsin Yang; Ki Hyeong Lee; Shun Lu; Yuankai Shi; Sang-We Kim; Janessa Laskin; Dong-Wan Kim; Catherine Dubos Arvis; Karl Kölbeck; Scott A Laurie; Chun-Ming Tsai; Mehdi Shahidi; Miyoung Kim; Dan Massey; Victoria Zazulina; Luis Paz-Ares Journal: Lancet Oncol Date: 2016-04-12 Impact factor: 41.316
Authors: E A Eisenhauer; P Therasse; J Bogaerts; L H Schwartz; D Sargent; R Ford; J Dancey; S Arbuck; S Gwyther; M Mooney; L Rubinstein; L Shankar; L Dodd; R Kaplan; D Lacombe; J Verweij Journal: Eur J Cancer Date: 2009-01 Impact factor: 9.162
Authors: Lecia V Sequist; James Chih-Hsin Yang; Nobuyuki Yamamoto; Kenneth O'Byrne; Vera Hirsh; Tony Mok; Sarayut Lucien Geater; Sergey Orlov; Chun-Ming Tsai; Michael Boyer; Wu-Chou Su; Jaafar Bennouna; Terufumi Kato; Vera Gorbunova; Ki Hyeong Lee; Riyaz Shah; Dan Massey; Victoria Zazulina; Mehdi Shahidi; Martin Schuler Journal: J Clin Oncol Date: 2013-07-01 Impact factor: 44.544