Osimertinib in NSCLC: Real-World Data From New Zealand

Abstract

Introduction: EGFR tyrosine kinase inhibitors (TKIs) are more effective than chemotherapy in patients with EGFRmutant NSCLC. Disease progression on EGFR TKI therapy occurs most often owing to acquired resistance from the gain of an EGFR T790M mutation. Osimertinib, a thirdgeneration EGFR TKI, significantly improves outcomes in patients with EGFR T790M mutation-positive NSCLC compared with platinum-pemetrexed chemotherapy. We retrospectively reviewed clinical outcomes for patients receiving osimertinib through a compassionate access program in New Zealand. Methods: Patients with a biopsy-proven or plasmacirculating tumor-DNA-proven EGFR T790M mutation received osimertinib. Data on patient and tumor characteristics, treatments, and outcomes were collected retrospectively. Survival outcomes were calculated from the time of osimertinib commencement. Results: A total of 39 patients were enrolled, and data from 37 patients were analyzed. EGFR T790M status was found from plasma samples in six of 37 (16%) patients. A total of 27 of 37 patients (73%) used osimertinib as a second-line treatment. At the time of data analysis, median follow-up was 18.8 months (range 1.5-29). Overall response rate was 70% (95% confidence interval [CI]: 53-84) (26 of 37). Progression-free survival (PFS) at 12 months was 62% (95% CI: 44.8-77.5), and median PFS was 14.6 months (95% CI: 12.4-16.8). Median overall survival was not reached. Osimertinib was well tolerated, with grade 1 gastrointestinal and skin toxicity as the most common adverse effects. Three patients required dose adjustments or cessation owing to toxicity. Conclusion: Osimertinib is an effective treatment for New Zealanders with EGFR T790M mutated NSCLC who have progressed after first or subsequent lines of therapy.

Real-World Data on Treatment Outcomes in EGFR -Mutant Non-Small-Cell Lung Cancer Patients Receiving Osimertinib in Second or Further Lines

“…Moreover, in our case series, 39.0% of patients received a local ablative treatment after osimertinib progression and 29.7% after post-TKI systemic chemotherapy in the T790Mgroup. Similarly, in published real-world data, 36.8-62% of the patients receiving osimertinib continued the drug beyond disease progression, in association with a local ablative therapy in 14-69% of patients [34][35][36][37]40,41].…”

“…Other real-world studies have recently reported outcomes and response rates in line with pivotal trials, even though the added value of our study is the inclusion of a T790Mgroup [28][29][30][31][32][34][35][36][38][39][40][41]43]. In real-world studies, a variable rate of patients received a subsequent treatment after osimertinib failure [29,[34][35][36][37].…”

“…Previous analysis of the pattern of recurrence with early-generation TKIs reported a more aggressive tumor behavior in T790M + patients, characterized by more new sites of disease compared with negative cases [27]. Several studies investigated the efficacy and safety of osimertinib in the real world in T790M+ patients among Asian [28][29][30][31][32][33], Caucasian [34][35][36][37][38] and both populations [39][40][41]. However, few data about progression patterns with osimertinib are available in T790M + patients, and previous studies did not include a T790Mcontrol group [30,33,34,36,37].…”

A Real-World Study of Patient Characteristics and Clinical Outcomes in EGFR Mutated Lung Cancer Treated with First-Line Osimertinib: Expanding the FLAURA Trial Results into Routine Clinical Practice

“… * Both deaths determined to be unrelated to osimertinib or lung cancer but occurring prior to the 6-week assessment time point. DCR calculated as complete response, partial response, and stable disease for ≥6 weeks within FLAURA clinical trial references [ 13 , 15 ], while it was collated as a lack of physician-determined clinical plus radiographic progression in the real-world BIDMC cohort. …”

“…Prior studies have evaluated real-world experiences with Osimertinib, but the majority focus on the experience of patients treated in the second-line, third-line, and beyond settings with tumors harboring EGFR -T790M [ 12 , 13 , 14 , 15 ]. Many of these real-world studies only focus on patterns of progression and mechanisms of resistance following initial progression on osimertinib [ 16 , 17 , 18 , 19 ].…”