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)

Yukari Tsubata,Ryota Saito,Daisuke Jingu,Kunihiko Kobayashi,Naoki Furuya,Kensuke Nakazawa,Hiroshige Yoshioka,Makoto Maemondo,Satoshi Morita,Kana Watanabe,Mami Morita,Yuki Akazawa,Susumu Takeuchi,Eiki Ichihara,Ryoichi Honda,Nobuhiro Kanaji,Satoshi Ohizumi,Atsuto Mouri,Kiyonori Miura ,Atsushi Nakamura,Taku Nagao ,Takeshi Isobe

doi:10.1007/s10147-021-02043-2

Abstract

BackgroundOsimertinib 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.MethodsEnrolled 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.ResultsThirty-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.ConclusionOsimertinib 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.

Highlights

Epidermal growth factor receptor (EGFR) gene mutations are the most common driver oncogene mutations associated with non-small cell lung cancer (NSCLC), accounting for 55% of driver oncogene mutations in lung adenocarcinoma cases in East Asia [1]
We confirmed that osimertinib is both efficacious and safe, which is beneficial for routine medical practice and therapeutic options for patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) resistance and poor performance status (PS), for T790M-positive patients with no other treatment options
This was a phase II investigator-initiated clinical trial conducted in patients who were T790M positive with a PS score of 2–4 and at least one failed EGFR-TKI treatment regimen

Summary

Introduction

Epidermal growth factor receptor (EGFR) gene mutations are the most common driver oncogene mutations associated with non-small cell lung cancer (NSCLC), accounting for 55% of driver oncogene mutations in lung adenocarcinoma cases in East Asia [1]. The recommended treatments for stage IV EGFR-positive lung cancer are EGFRtyrosine kinase inhibitor (TKI) monotherapy, EGFR-TKI plus cytotoxic combination chemotherapy, and EGFR-TKI. The EGFR T790M mutation is considered a cause of acquired resistance to EGFR-TKI therapy and is found in approximately 60% of patients with lung adenocarcinoma treated with EGFR-TKIs [8, 9]. A clinical trial comparing osimertinib with pemetrexed plus either carboplatin or cisplatin in patients with EGFR T790M mutation-positive NSCLC and with disease progression after first-line therapy reported significantly longer PFS (10.1 months vs 4.4 months) and significantly better. 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). 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

Methods

Results

Conclusion