Final Analysis Data and Exploratory Biomarker Analysis of a Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib Monotherapy for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: The WJOG9717L Study

Hirotsugu Kenmotsu, MD, PhD; Kazuko Sakai, PhD; Keita Mori, PhD; Terufumi Kato, MD; Shunichi Sugawara, MD, PhD; Keisuke Kirita, MD, PhD; Yasuto Yoneshima, MD, PhD; Koichi Azuma, MD, PhD; Kazumi Nishino, MD, PhD; Shunsuke Teraoka, MD; Ryo Koyama, MD, PhD; Ken Masuda, MD, PhD; Hidetoshi Hayashi, MD, PhD; Ryo Toyozawa, MD, PhD; Satoru Miura, MD, PhD; Yuki Sato, MD, PhD; Kazuhiko Nakagawa, MD, PhD; Nobuyuki Yamamoto, MD, PhD; Kazuto Nishio, MD, PhD; Toshiaki Takahashi, MD, PhD

JTO Clinical and Research Reports (Nov 2024)

Final Analysis Data and Exploratory Biomarker Analysis of a Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib Monotherapy for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: The WJOG9717L Study

Hirotsugu Kenmotsu, MD, PhD,
Kazuko Sakai, PhD,
Keita Mori, PhD,
Terufumi Kato, MD,
Shunichi Sugawara, MD, PhD,
Keisuke Kirita, MD, PhD,
Yasuto Yoneshima, MD, PhD,
Koichi Azuma, MD, PhD,
Kazumi Nishino, MD, PhD,
Shunsuke Teraoka, MD,
Ryo Koyama, MD, PhD,
Ken Masuda, MD, PhD,
Hidetoshi Hayashi, MD, PhD,
Ryo Toyozawa, MD, PhD,
Satoru Miura, MD, PhD,
Yuki Sato, MD, PhD,
Kazuhiko Nakagawa, MD, PhD,
Nobuyuki Yamamoto, MD, PhD,
Kazuto Nishio, MD, PhD,
Toshiaki Takahashi, MD, PhD

Affiliations

Hirotsugu Kenmotsu, MD, PhD: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Japan; Corresponding author. Address for correspondence: Hirotsugu Kenmotsu, MD, PhD, Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777, Japan.
Kazuko Sakai, PhD: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan
Keita Mori, PhD: Clinical Research Center, Shizuoka Cancer Center Nagaizumi-cho, Japan
Terufumi Kato, MD: Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan
Shunichi Sugawara, MD, PhD: Department of Pulmonary Medicine, Sendai Kousei Hospital, Miyagi, Japan
Keisuke Kirita, MD, PhD: Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
Yasuto Yoneshima, MD, PhD: Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Koichi Azuma, MD, PhD: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan
Kazumi Nishino, MD, PhD: Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
Shunsuke Teraoka, MD: Internal Medicine III, Wakayama Medical University, Wakayama, Japan
Ryo Koyama, MD, PhD: Department of Respiratory Medicine, Juntendo University, Tokyo, Japan
Ken Masuda, MD, PhD: Department of Respiratory Medicine, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
Hidetoshi Hayashi, MD, PhD: Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan
Ryo Toyozawa, MD, PhD: Department of Thoracic Oncology, NHO Kyushu Cancer Center, Fukuoka, Japan
Satoru Miura, MD, PhD: Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan
Yuki Sato, MD, PhD: Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Hyogo, Japan
Kazuhiko Nakagawa, MD, PhD: Department of Medical Oncology, Faculty of Medicine, Kindai University, Osaka-Sayama, Japan
Nobuyuki Yamamoto, MD, PhD: Internal Medicine III, Wakayama Medical University, Wakayama, Japan
Kazuto Nishio, MD, PhD: Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan
Toshiaki Takahashi, MD, PhD: Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Japan

Journal volume & issue: Vol. 5, no. 11
p. 100716

Abstract

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Introduction: EGFR tyrosine kinase inhibitors have been the standard treatment for patients with NSCLC who have sensitive EGFR mutations. This study revealed final analysis survival data, biomarkers, and resistance mechanisms of osimertinib plus bevacizumab or osimertinib monotherapy in previously untreated patients with advanced EGFR-positive nonsquamous NSCLC. Methods: We previously reported the primary results of a randomized, open-label, phase 2 study comparing osimertinib plus bevacizumab with osimertinib monotherapy for this population. In this exploratory analysis using tissue and plasma samples, we evaluated gene profiles at baseline and disease progression or the last dose using targeted deep sequencing. Results: The median progression-free survival (PFS) by the blinded independent central reviewer was 22.1 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (hazard ratio [HR] = 0.864, 95% confidence interval [CI]: 0.549–1.359). The 3-year overall survival was not different between the two arms (osimertinib plus bevacizumab: 57.1%; osimertinib monotherapy: 65.0%; HR 1.271, 95% CI: 0.727–2.223). A total of 94 patients had assessable plasma samples at baseline, and 40 had assessable pretreatment tissue samples. EGFR mutations (76.6%) and TP53 mutations (44.7%) were detected in plasma samples at baseline. In patients with plasma TP53 mutations (n = 42), the median PFS by blinded independent central reviewer was 19.8 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (HR = 1.107, 95% CI: 0.534–2.297). Conclusions: There was also no significant difference in the PFS between the two arms, even in patients with TP53 mutations.

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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