Osimertinib for patients with poor performance status and EGFR T790M mutation-positive advanced non-small cell lung cancer: a phase II clinical trial

Abstract

Osimertinib is a molecularly targeted agent used to treat non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) T790M mutation. However, its efficacy and safety profile when patients have poor performance status (PS) is unknown. Therefore, we conducted an open-label, multi-center, single-arm phase II study to evaluate its efficacy and safety in EGFR T790M mutation-positive NSCLC patients with Eastern Cooperative Oncology Group PS scores of between 2 and 4. Patients received 80 mg of osimertinib once daily. Our primary endpoint was progression-free survival. Eighteen patients were enrolled between June 2017 and November 2018. The median age was 77 years (range: 55-85 years). Ten, six, and two patients had PS scores of 2, 3, and 4, respectively. All patients had adenocarcinoma with common EGFR mutations and had been treated with first-or second-generation EGFR-tyrosine kinase inhibitors previously. The overall median progression-free survival was 7.0 months (90% confidence interval: 5.5-8.9 months). The overall response rate and median overall survival were 53% and 12.7 months, respectively. Moreover, improved PS scores were observed in 72% of the patients. Although the incidence of grade 3 adverse events was low, with no grade 4 or 5 events observed, three patients required treatment cessation due to the development of interstitial lung disease. Osimertinib therapy could be beneficial for EGFR T790M mutation-positive advanced NSCLC patients with poor PS. This trial was registered with the Japan Registry of Clinical Trials on March 12, 2019 (trial no. jRCT1041180081).

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“…Some molecularly targeted agents, including osimertinib, which have a high response and disease control rates, can be effective against advanced-stage patients with NSCLC who have poor condition. 5 Generally, ADCs including T-DXd, which use a cleavable linker payload system, are safety due to their tumor-specific effects. 6 , 7 The Linker payload system of ADCs is generally cut specifically in tumors to release cytotoxic agents, which have antitumor effects.…”

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)

“…In these clinical studies, the RR with osimertinib was 71% and 66%, respectively. Meanwhile, Nakashima et al reported a 53% RR in prospective phase II study of poor PS [ 16 ]. The RR in our study not only met the study endpoint statistically but was also excellent considering that this study was conducted in older patients with poor PS.…”

International consensus on severe lung cancer—the first edition

“…In addition, the treatment was well tolerated (165). Similarly, osimertinib also appears to be effective (median PFS: 7.0 months; median OS: 12.7 months) in a recent phase II trial enrolling 18 patients with T790Mmutated NSCLC with PS ≥2, and it improved the PS score in 72% of the patients (166).…”