Osimertinib and Bevacizumab Cotreatment for Untreated EGFR-Mutated NSCLC With Malignant Pleural or Pericardial Effusion (SPIRAL II): A Single-Arm, Open-Label, Phase 2 Clinical Trial
Introduction: First-line treatment of EGFR-mutated NSCLC with erlotinib plus antiangiogenic inhibitor exhibits promising results. However, the efficacy of this combination has not been fully investigated. Therefore, we evaluated the efficacy and safety of osimertinib plus bevacizumab in patients wit...
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Elsevier
2022-12-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364322001485 |
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| author | Makoto Hibino, MD Osamu Hiranuma, MD Yoshizumi Takemura, MD, PhD Yuki Katayama, MD Yusuke Chihara, MD, PhD Taishi Harada, MD Kohei Fujita, MD, PhD Toshiyuki Kita, MD, PhD Nobuyo Tamiya, MD, PhD Takeshi Tsuda, MD Shinsuke Shiotsu, MD Yukihiro Tamura, MD, PhD Takashi Aoyama, MD Yoichi Nakamura, MD, PhD Masaaki Terashima, MD, PhD Yoshie Morimoto, MD, PhD Kazuhiro Nagata, MD, PhD Kenichi Yoshimura, PhD Junji Uchino, MD, PhD Koichi Takayama, MD, PhD |
| author_facet | Makoto Hibino, MD Osamu Hiranuma, MD Yoshizumi Takemura, MD, PhD Yuki Katayama, MD Yusuke Chihara, MD, PhD Taishi Harada, MD Kohei Fujita, MD, PhD Toshiyuki Kita, MD, PhD Nobuyo Tamiya, MD, PhD Takeshi Tsuda, MD Shinsuke Shiotsu, MD Yukihiro Tamura, MD, PhD Takashi Aoyama, MD Yoichi Nakamura, MD, PhD Masaaki Terashima, MD, PhD Yoshie Morimoto, MD, PhD Kazuhiro Nagata, MD, PhD Kenichi Yoshimura, PhD Junji Uchino, MD, PhD Koichi Takayama, MD, PhD |
| author_sort | Makoto Hibino, MD |
| collection | DOAJ |
| description | Introduction: First-line treatment of EGFR-mutated NSCLC with erlotinib plus antiangiogenic inhibitor exhibits promising results. However, the efficacy of this combination has not been fully investigated. Therefore, we evaluated the efficacy and safety of osimertinib plus bevacizumab in patients with EGFR-mutated NSCLC complicated with malignant pleural or pericardial effusion (MPE) for whom combination therapy may be particularly effective. Methods: This single-arm, open-label, phase 2 study aimed to investigate the clinical benefits of the bevacizumab (15 mg/kg) and osimertinib (80 mg) combination in the first-line setting for advanced EGFR-mutated NSCLC with MPE. The primary end point of this study was 1-year progression-free survival (PFS). The secondary end points were objective response rate, PFS, overall survival, drainage-free survival without the need for thoracic or pericardial drainage, and safety. Results: Between January 2019 and August 2020, a total of 31 patients with EGFR-mutated NSCLC were enrolled from Japan in the study. The median PFS was 8.5 months (95% confidence interval [CI]: 5.3–11.3), the 1-year PFS was 32.1% (80% CI: 21.4–43.3), and the objective response rate was 74.2% (95% CI: 56.8–86.3). The median overall survival was not reached. The median drainage-free survival was 18.4 months (95% CI: 10.3–not estimable). Anorexia was the most common grade 3 or higher adverse event (four patients, 12.9%), followed by fatigue and dyspnea (three patients, 9.7%). No treatment-related deaths were recorded. Conclusions: Osimertinib and bevacizumab combination in patients with advanced EGFR-mutated NSCLC with MPE were safe but did not effectively increase PFS when compared with the inferred value from previous literature. |
| first_indexed | 2024-04-12T01:48:34Z |
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| id | doaj.art-a09bdb92643c488189791c1af982e3fb |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-04-12T01:48:34Z |
| publishDate | 2022-12-01 |
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| series | JTO Clinical and Research Reports |
| spelling | doaj.art-a09bdb92643c488189791c1af982e3fb2022-12-22T03:53:00ZengElsevierJTO Clinical and Research Reports2666-36432022-12-01312100424Osimertinib and Bevacizumab Cotreatment for Untreated EGFR-Mutated NSCLC With Malignant Pleural or Pericardial Effusion (SPIRAL II): A Single-Arm, Open-Label, Phase 2 Clinical TrialMakoto Hibino, MD0Osamu Hiranuma, MD1Yoshizumi Takemura, MD, PhD2Yuki Katayama, MD3Yusuke Chihara, MD, PhD4Taishi Harada, MD5Kohei Fujita, MD, PhD6Toshiyuki Kita, MD, PhD7Nobuyo Tamiya, MD, PhD8Takeshi Tsuda, MD9Shinsuke Shiotsu, MD10Yukihiro Tamura, MD, PhD11Takashi Aoyama, MD12Yoichi Nakamura, MD, PhD13Masaaki Terashima, MD, PhD14Yoshie Morimoto, MD, PhD15Kazuhiro Nagata, MD, PhD16Kenichi Yoshimura, PhD17Junji Uchino, MD, PhD18Koichi Takayama, MD, PhD19Department of Respiratory Medicine, Shonan Fujisawa Tokushukai Hospital, Fujisawa, JapanDepartment of Pulmonary Medicine, Otsu City Hospital, Otsu, JapanDepartment of Pulmonary Medicine, Otsu City Hospital, Otsu, JapanDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, JapanDepartment of Respiratory Medicine, Uji Tokushukai Medical Center, Uji, JapanMedical Oncology, Fukuchiyama City Hospital, Fukuchiyama, JapanDivision of Respiratory Medicine, Center for Respiratory Diseases, National Hospital Organization Kyoto Medical Center, Fushimi, JapanDepartment of Respiratory Medicine, National Hospital Organization Kanazawa Medical Center, Kanazawa, JapanDepartment of Respitaroy Medicine, Rakuwakai Otowa Hospital, Kyoto, JapanDepartment of Respiratory Medicine, Toyama Prefectural Central Hospital, Toyama, JapanDepartment of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, JapanInternal Medicine, Oosumi Kanoya Hospital, Kanoya, JapanDepartment of Respiratory Medicine, Fukuoka University Hospital, Fukuoka, JapanDivision of Thoracic Oncology, Tochigi Cancer Center, Utsunomiya, JapanDepartment of Medical Oncology, Izumi City General Hospital, Osaka, JapanDepartment of Pulmonary Medicine, Kyoto Kuramaguchi Medical Center, Kyoto, JapanRespiratory Center, Koseikai Takeda Hospital, Kyoto, JapanMedical Center for Translational and Clinical Research, Hiroshima University, Hiroshima, JapanDepartment of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Corresponding author. Address for correspondence: Junji Uchino, MD, PhD, Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachihirokoji, Kamigyoku, Kyoto 602-8566, Japan.Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, JapanIntroduction: First-line treatment of EGFR-mutated NSCLC with erlotinib plus antiangiogenic inhibitor exhibits promising results. However, the efficacy of this combination has not been fully investigated. Therefore, we evaluated the efficacy and safety of osimertinib plus bevacizumab in patients with EGFR-mutated NSCLC complicated with malignant pleural or pericardial effusion (MPE) for whom combination therapy may be particularly effective. Methods: This single-arm, open-label, phase 2 study aimed to investigate the clinical benefits of the bevacizumab (15 mg/kg) and osimertinib (80 mg) combination in the first-line setting for advanced EGFR-mutated NSCLC with MPE. The primary end point of this study was 1-year progression-free survival (PFS). The secondary end points were objective response rate, PFS, overall survival, drainage-free survival without the need for thoracic or pericardial drainage, and safety. Results: Between January 2019 and August 2020, a total of 31 patients with EGFR-mutated NSCLC were enrolled from Japan in the study. The median PFS was 8.5 months (95% confidence interval [CI]: 5.3–11.3), the 1-year PFS was 32.1% (80% CI: 21.4–43.3), and the objective response rate was 74.2% (95% CI: 56.8–86.3). The median overall survival was not reached. The median drainage-free survival was 18.4 months (95% CI: 10.3–not estimable). Anorexia was the most common grade 3 or higher adverse event (four patients, 12.9%), followed by fatigue and dyspnea (three patients, 9.7%). No treatment-related deaths were recorded. Conclusions: Osimertinib and bevacizumab combination in patients with advanced EGFR-mutated NSCLC with MPE were safe but did not effectively increase PFS when compared with the inferred value from previous literature.http://www.sciencedirect.com/science/article/pii/S2666364322001485Angiogenesis inhibitorBevacizumabEGFR tyrosine kinase inhibitorsOsimertinibVascular endothelial growth factor |
| spellingShingle | Makoto Hibino, MD Osamu Hiranuma, MD Yoshizumi Takemura, MD, PhD Yuki Katayama, MD Yusuke Chihara, MD, PhD Taishi Harada, MD Kohei Fujita, MD, PhD Toshiyuki Kita, MD, PhD Nobuyo Tamiya, MD, PhD Takeshi Tsuda, MD Shinsuke Shiotsu, MD Yukihiro Tamura, MD, PhD Takashi Aoyama, MD Yoichi Nakamura, MD, PhD Masaaki Terashima, MD, PhD Yoshie Morimoto, MD, PhD Kazuhiro Nagata, MD, PhD Kenichi Yoshimura, PhD Junji Uchino, MD, PhD Koichi Takayama, MD, PhD Osimertinib and Bevacizumab Cotreatment for Untreated EGFR-Mutated NSCLC With Malignant Pleural or Pericardial Effusion (SPIRAL II): A Single-Arm, Open-Label, Phase 2 Clinical Trial JTO Clinical and Research Reports Angiogenesis inhibitor Bevacizumab EGFR tyrosine kinase inhibitors Osimertinib Vascular endothelial growth factor |
| title | Osimertinib and Bevacizumab Cotreatment for Untreated EGFR-Mutated NSCLC With Malignant Pleural or Pericardial Effusion (SPIRAL II): A Single-Arm, Open-Label, Phase 2 Clinical Trial |
| title_full | Osimertinib and Bevacizumab Cotreatment for Untreated EGFR-Mutated NSCLC With Malignant Pleural or Pericardial Effusion (SPIRAL II): A Single-Arm, Open-Label, Phase 2 Clinical Trial |
| title_fullStr | Osimertinib and Bevacizumab Cotreatment for Untreated EGFR-Mutated NSCLC With Malignant Pleural or Pericardial Effusion (SPIRAL II): A Single-Arm, Open-Label, Phase 2 Clinical Trial |
| title_full_unstemmed | Osimertinib and Bevacizumab Cotreatment for Untreated EGFR-Mutated NSCLC With Malignant Pleural or Pericardial Effusion (SPIRAL II): A Single-Arm, Open-Label, Phase 2 Clinical Trial |
| title_short | Osimertinib and Bevacizumab Cotreatment for Untreated EGFR-Mutated NSCLC With Malignant Pleural or Pericardial Effusion (SPIRAL II): A Single-Arm, Open-Label, Phase 2 Clinical Trial |
| title_sort | osimertinib and bevacizumab cotreatment for untreated egfr mutated nsclc with malignant pleural or pericardial effusion spiral ii a single arm open label phase 2 clinical trial |
| topic | Angiogenesis inhibitor Bevacizumab EGFR tyrosine kinase inhibitors Osimertinib Vascular endothelial growth factor |
| url | http://www.sciencedirect.com/science/article/pii/S2666364322001485 |
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