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

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

JTO Clinical and Research Reports (Dec 2022)

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

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

Affiliations

Makoto Hibino, MD: Department of Respiratory Medicine, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Japan
Osamu Hiranuma, MD: Department of Pulmonary Medicine, Otsu City Hospital, Otsu, Japan
Yoshizumi Takemura, MD, PhD: Department of Pulmonary Medicine, Otsu City Hospital, Otsu, Japan
Yuki Katayama, MD: Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
Yusuke Chihara, MD, PhD: Department of Respiratory Medicine, Uji Tokushukai Medical Center, Uji, Japan
Taishi Harada, MD: Medical Oncology, Fukuchiyama City Hospital, Fukuchiyama, Japan
Kohei Fujita, MD, PhD: Division of Respiratory Medicine, Center for Respiratory Diseases, National Hospital Organization Kyoto Medical Center, Fushimi, Japan
Toshiyuki Kita, MD, PhD: Department of Respiratory Medicine, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan
Nobuyo Tamiya, MD, PhD: Department of Respitaroy Medicine, Rakuwakai Otowa Hospital, Kyoto, Japan
Takeshi Tsuda, MD: Department of Respiratory Medicine, Toyama Prefectural Central Hospital, Toyama, Japan
Shinsuke Shiotsu, MD: Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
Yukihiro Tamura, MD, PhD: Internal Medicine, Oosumi Kanoya Hospital, Kanoya, Japan
Takashi Aoyama, MD: Department of Respiratory Medicine, Fukuoka University Hospital, Fukuoka, Japan
Yoichi Nakamura, MD, PhD: Division of Thoracic Oncology, Tochigi Cancer Center, Utsunomiya, Japan
Masaaki Terashima, MD, PhD: Department of Medical Oncology, Izumi City General Hospital, Osaka, Japan
Yoshie Morimoto, MD, PhD: Department of Pulmonary Medicine, Kyoto Kuramaguchi Medical Center, Kyoto, Japan
Kazuhiro Nagata, MD, PhD: Respiratory Center, Koseikai Takeda Hospital, Kyoto, Japan
Kenichi Yoshimura, PhD: Medical Center for Translational and Clinical Research, Hiroshima University, Hiroshima, Japan
Junji Uchino, MD, PhD: Department 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.
Koichi Takayama, MD, PhD: Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

Journal volume & issue: Vol. 3, no. 12
p. 100424

Abstract

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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.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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