Hirotsugu Kenmotsu1, Kazushige Wakuda2, Keita Mori3, Terufumi Kato4, Shunichi Sugawara5, Keisuke Kirita6, Yasuto Yoneshima7, Koichi Azuma8, Kazumi Nishino9, Shunsuke Teraoka10, Takehito Shukuya11, Ken Masuda12, Hidetoshi Hayashi13, Ryo Toyozawa14, Satoru Miura15, Daichi Fujimoto16, Kazuhiko Nakagawa13, Nobuyuki Yamamoto10, Toshiaki Takahashi2. 1. Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi, Japan. Electronic address: h.kenmotsu@scchr.jp. 2. Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi, Japan. 3. Clinical Research Center, Shizuoka Cancer Center, Nagaizumi, Japan. 4. Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan. 5. Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi, Japan. 6. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 7. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 8. Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan. 9. Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan. 10. Internal Medicine III, Wakayama Medical University, Wakayama, Japan. 11. Department of Respiratory Medicine, Juntendo University, Tokyo, Japan. 12. Department of Respiratory Medicine, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan. 13. Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka, Japan. 14. Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 15. Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. 16. Internal Medicine III, Wakayama Medical University, Wakayama, Japan; Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Hyogo, Japan.
Abstract
INTRODUCTION: To evaluate the efficacy and safety of osimertinib plus bevacizumab for previously untreated patients with advanced nonsquamous NSCLC harboring EGFR-sensitizing mutations. METHODS: We conducted a randomized, open-label, phase 2 study at 21 institutions in Japan. Previously untreated patients with advanced nonsquamous NSCLC harboring EGFR-sensitizing mutations received either osimertinib (80 mg, daily) plus bevacizumab (15 mg/kg, every 3 wk) or osimertinib monotherapy, and were stratified according to sex, stage, and EGFR mutation status. The primary end point was progression-free survival (PFS) in the intention-to-treat population, assessed by means of blinded, independent central radiologic review. RESULTS: Between January 2018 and September 2018, a total of 122 patients were enrolled (osimertinib + bevacizumab arm, 61 patients; osimertinib monotherapy arm, 61 patients). At a median follow-up duration of 19.8 months, the median PFS was 22.1 months for osimertinib plus bevacizumab and 20.2 months for osimertinib monotherapy, with a hazard ratio of 0.862 (60% confidence interval: 0.700-1.060, 95% confidence interval: 0.531-1.397, one-sided stratified log-rank p = 0.213). Adverse events of grade 3 or worse were observed in 34 patients (56%) in the osimertinib plus bevacizumab arm and 29 (48%) in the osimertinib monotherapy arm. In addition, two (3%) and 11 patients (18%) experienced any grade pneumonitis, respectively, and grade 3 pneumonitis was observed in one patient (2%) in each arm. CONCLUSIONS: This study failed to exhibit the efficacy of osimertinib plus bevacizumab for improving the PFS among patients with nonsquamous NSCLC harboring EGFR mutations as first-line treatment.
INTRODUCTION: To evaluate the efficacy and safety of osimertinib plus bevacizumab for previously untreated patients with advanced nonsquamous NSCLC harboring EGFR-sensitizing mutations. METHODS: We conducted a randomized, open-label, phase 2 study at 21 institutions in Japan. Previously untreated patients with advanced nonsquamous NSCLC harboring EGFR-sensitizing mutations received either osimertinib (80 mg, daily) plus bevacizumab (15 mg/kg, every 3 wk) or osimertinib monotherapy, and were stratified according to sex, stage, and EGFR mutation status. The primary end point was progression-free survival (PFS) in the intention-to-treat population, assessed by means of blinded, independent central radiologic review. RESULTS: Between January 2018 and September 2018, a total of 122 patients were enrolled (osimertinib + bevacizumab arm, 61 patients; osimertinib monotherapy arm, 61 patients). At a median follow-up duration of 19.8 months, the median PFS was 22.1 months for osimertinib plus bevacizumab and 20.2 months for osimertinib monotherapy, with a hazard ratio of 0.862 (60% confidence interval: 0.700-1.060, 95% confidence interval: 0.531-1.397, one-sided stratified log-rank p = 0.213). Adverse events of grade 3 or worse were observed in 34 patients (56%) in the osimertinib plus bevacizumab arm and 29 (48%) in the osimertinib monotherapy arm. In addition, two (3%) and 11 patients (18%) experienced any grade pneumonitis, respectively, and grade 3 pneumonitis was observed in one patient (2%) in each arm. CONCLUSIONS: This study failed to exhibit the efficacy of osimertinib plus bevacizumab for improving the PFS among patients with nonsquamous NSCLC harboring EGFR mutations as first-line treatment.
Authors: Francesco Passiglia; Paolo Bironzo; Valentina Bertaglia; Angela Listì; Edoardo Garbo; Giorgio Vittorio Scagliotti Journal: Transl Lung Cancer Res Date: 2022-05
Authors: U Dafni; R A Soo; S Peters; Z Tsourti; P Zygoura; K Vervita; J-Y Han; J De Castro; L Coate; M Früh; S M S Hashemi; E Nadal; E Carcereny; M A Sala; R Bernabé; M Provencio; S Cuffe; H Roschitzki-Voser; B Ruepp; R Rosell; R A Stahel Journal: ESMO Open Date: 2022-06-10