Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B)
Year: 2021
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown. METHODS: Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2-4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety. RESULTS: Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3-5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations. CONCLUSION: Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.
Authors: Yukari Tsubata, Kana Watanabe, Ryota Saito, Atsushi Nakamura, Hiroshige Yoshioka, Mami Morita, Ryoichi Honda, Nobuhiro Kanaji, Satoshi Ohizumi, Daisuke Jingu, Taku Nakagawa, Kensuke Nakazawa, Atsuto Mouri, Susumu Takeuchi, Naoki Furuya, Yuki Akazawa, Kiyotaka Miura, Eiki Ichihara, Makoto Maemondo, Satoshi Morita, Kunihiko Kobayashi, Takeshi Isobe
Institutions: Shimane University, Miyagi Prefectural Hospital Organization, Tohoku University Hospital, Sendai Kousei Hospital, Kansai Medical University Hospital, Asahi General Hospital, Kagawa University, Sapporo National Hospital, Saka General Hospital, Omagari Kousei Medical Center, University of Tsukuba, Saitama International Medical Center, Saitama Medical University, Tokyo Medical University, St. Marianna University School of Medicine, National Hospital Organization, Shimane Prefectural Central Hospital, Okayama University Hospital, Iwate Medical University, Kyoto University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,860
OpenAlex ID: W3207801650