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Clinical Trial
. 2025 May;20(5):665-675.
doi: 10.1016/j.jtho.2024.12.027. Epub 2025 Jan 2.

A Prospective Phase II Trial of First-Line Osimertinib for Patients With EGFR Mutation-Positive NSCLC and Poor Performance Status (OPEN/TORG2040)

Tomoya Fukui  1 , Nobuaki Mamesaya  2 , Toshiaki Takahashi  2 , Kazuma Kishi  3 , Takahiro Yoshizawa  3 , Takaaki Tokito  4 , Koichi Azuma  4 , Kei Morikawa  5 , Satoshi Igawa  6 , Yusuke Okuma  7 , Yuta Yamanaka  8 , Shinobu Hosokawa  9 , Takashi Kasai  10 , Ken Masubuchi  11 , Shinji Nakamichi  12 , Masaharu Aga  13 , Jiichiro Sasaki  14 , Akiko Kada  15 , Akiko M Saito  15 , Katsuhiko Naoki  6 , Hiroaki Okamoto  13 ; Thoracic Oncology Research Group (TORG)
Affiliations
Clinical Trial

A Prospective Phase II Trial of First-Line Osimertinib for Patients With EGFR Mutation-Positive NSCLC and Poor Performance Status (OPEN/TORG2040)

Tomoya Fukui et al. J Thorac Oncol. 2025 May.

Abstract

Introduction: Osimertinib is the first-line treatment for patients with NSCLC who have EGFR mutations and favorable performance status (PS). Despite the increasing clinical data on osimertinib, evidence for its use in patients with impaired PS remains limited. Therefore, a multicenter phase II trial (OPEN/TORG2040) was conducted to evaluate the efficacy and safety of first-line osimertinib treatment in patients with EGFR mutation-positive NSCLC and a poor PS.

Methods: Patients with previously untreated advanced NSCLC harboring EGFR-sensitizing mutations and PS of 2 to 4 were enrolled. Osimertinib (80 mg once daily) was orally administered to eligible patients. The primary end point was objective response rate. The secondary end points were disease control rate, PS improvement rate, patient-reported outcomes, and safety.

Results: Between February 2021 and February 2022, 30 patients with poor PS (22 with a PS of 2, six with a PS of 3, and two with a PS of 4) were enrolled. The median age was 75 (range, 41-92) years, and 18 patients had brain metastases. The objective response rate was 63.3% (90% confidence interval, 46.7%-77.9%; one-sided, p = 0.033). Disease control and PS improvement rates were 93.3% and 63.3%, respectively. Global health status/QoL also improved. Median progression-free and overall survival were 8.0 and 25.4 months, respectively. Eight patients (26.7%) experienced serious adverse events leading to discontinuation, and six (20.0%) experienced interstitial lung disease.

Conclusions: This prospective study confirmed the efficacy of first-line osimertinib treatment in patients with EGFR mutation-positive NSCLC and poor PS, highlighting the need for interstitial lung disease risk management.

Trial registration number: Japan Registry of Clinical Trials Identifier: jRCTs041200100.

Keywords: EGFR; Non–small cell lung cancer; Osimertinib; Poor performance status; Quality of life.

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Conflict of interest statement

Disclosure Dr. Fukui received research support from AstraZeneca for this manuscript and honoraria from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, Eli Lilly Japan, Merck Sharp & Dohme, Nippon Kayaku, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, and Takeda Pharmaceutical. Dr. Mamesaya received research grants from Merck Sharp & Dohme, Chugai Pharmaceutical, and Arrivent Biopharma and honoraria from Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Merck Sharp & Dohme, Ono Pharmaceutical, and Novartis Pharma. Dr. Takahashi received research grants from AstraZeneca, Eli Lilly Japan, Chugai Pharmaceutical, Merck Sharp & Dohme, Pfizer Japan, Amgen, Merck Biopharma, Janssen Pharmaceutical, and AnHeart Therapeutics and honoraria from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Ono Pharmaceutical, Merck Sharp & Dohme, Pfizer Japan, Takeda Pharmaceutical, Bristol Myers Squibb, Amgen, and Novartis Pharma. Dr. Kishi received honoraria from AstraZeneca. Dr. Tokito has received honoraria from AstraZeneca, Ono Pharmaceutical, MSD Oncology, Chugai Pharmaceutical, Bristol Myers Squibb, Nippon Kayaku, and Boehringer Ingelheim. Dr. Azuma has received honoraria from AstraZeneca, Merck Sharp & Dohme, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, and Takeda Pharmaceutical. Dr. Morikawa has received honoraria from AstraZeneca, Boehringer Ingelheim, Chugai Pharmaceutical, Eli Lilly Japan, Merck Sharp & Dohme, and Takeda Pharmaceuticals. Dr. Okuma received research grants from Merck Sharp & Dohme, AstraZeneca, and Summit Therapeutics and honoraria from Boehringer Ingelheim, Chugai Pharmaceutical, Eisai, Eli Lilly Japan, Merck Sharp & Dohme, Ono Pharmaceutical, Taiho Pharmaceutical, and Takeda Pharmaceutical. Hosokawa received honoraria from AstraZeneca, Chugai Pharmaceutical, Bristol Myers Squibb, Ono Pharmaceutical, and Taiho Pharmaceutical. Dr. Nakamichi received honoraria from AstraZeneca, Chugai Pharmaceutical, Bristol Myers Squibb, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda Pharmaceutical, Merck Sharp & Dohme, and Merck Biopharma. Dr. Sasaki received honoraria from A2 Healthcare and AstraZeneca. Dr. Naoki received research support from AstraZeneca for this study; research grants from Boehringer Ingelheim, Chugai Pharmaceutical, Ono Pharmaceutical, Taiho Pharmaceutical, and Parexel International; and honoraria from AstraZeneca and Chugai Pharmaceutical. Dr. Okamoto received research grants from AstraZeneca, Taiho, Bristol, Myers Squibb, and Merck Sharp & Dohme. The remaining authors declare no conflict of interest.

Comment in

  • The OPEN trial-from the darkness, comes light.
    Pham R, Arulananda S. Pham R, et al. Transl Lung Cancer Res. 2025 Aug 31;14(8):2912-2917. doi: 10.21037/tlcr-2025-363. Epub 2025 Aug 11. Transl Lung Cancer Res. 2025. PMID: 40948852 Free PMC article. No abstract available.

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