Comparison of treatment outcomes in patients with metastatic lung cancer who did or did not develop EGFR T790M mutation.

Abstract

e21658 Background: First-line treatment of lung cancer patients with EGFR mutation with early generation tyrosine kinase inhibitors (TKIs) renders a median progression-free survival (mPFS) of 11 months (m), and for the patients who subsequently develop the T790M mutation, osimertinib provides an additional mPFS of 10 m. First-line treatment with osimertinib showed mPFS of 18.9 m and none developed T790M at the time of progression (FLAURA trial). We hypothesized that the mPFS for patients who developed T790M mutation might be longer than those who did not and the prognosis and outcome might be different between these two groups. Methods: This is a retrospective study on patients who were diagnosed with metastatic, EGFR-mutated NSCLC and treated at Maimonides Cancer Center between 1/1/2011 and 9/30/2019. Patients were divided into two cohorts: those who did not develop T790M mutation (group 1), and those who did (including 1 patient who had de novo mutation, group 2). Results: Fifty-six patients were identified, with median age of 70 years (range 40-93). All patients had adenocarcinoma. Thirty-nine (70%) were Chinese. There were 31 (55%) exon 19 deletion, 22 (39%) L858R, 1 E709A, 1 G719S and 1 de novo T790M mutations. Forty-five patients (80%) never developed T790M (group 1), 10 (18%) did and 1 had primary mutation (group 2). The median time to developing T790M mutation was 22 m. In group 1, 8 patients received first-line osimertinib, while other 37 received erlotinib (23), gefitinib (4) and afatinib (10). Among the 37 patients, 12 were switched to osimertinib in subsequent lines, 5 due to toxicity and 7 due to progression. In group 2, 8 patients received osimertinib at identification of T790M and 1 for de novo mutation. At 22 m median follow up, the mPFS for group 1 was 14 m (95% CI 9.3-19); the mPFS for group 2 was 21.6 m (95% CI 7.4-49.1) up to the time of identification of T790M, and 31.2 m (95% CI 4.9-45.4) until disease progression after osimertinib. The mPFS of the entire cohort was 17.1 m (95% 11.1-25.9), and mOS was 22.0 m (95% 15.6-29.6). The mOS was 19.0 m (95% CI 11.4 – 25.2), and 39.9 m (95% CI 13.3 – 62.1) for group 1 and 2 respectively. Conclusions: Patients who developed the T790M mutation appeared to have a longer PFS than those who did not and the mean duration to detection of T790M was 22 m. The development of T790M may confer a slower growth pattern and longer PFS. This question should be further explored in larger studies.