Totality outcome of afatinib sequential treatment in patients with EGFR mutation-positive NSCLC in Korea: KCSG LU-19-22.

Abstract

9053 Background: While osimertinib showed impressive efficacy and safety profile in 1st-line setting for EGFR mutation-positive (EGFR M+) NSCLC patients, there are no standard targeted therapy following progression. Thus, interest has been growing on sequential treatment of osimertinib as 2nd-line treatment for patients acquiring T790M resistance mutation after 2nd generation EGFR TKIs. We did a retrospective study to support the hypothesis that sequential approach of afatinib followed by osimertinib represents a practical treatment option in ‘real-world’ practice. Methods: In this non-interventional, multicenter study, EGFR M+ NSCLC patients had to start 1st-line afatinib treatment ≥ 13 months prior to data entry. They were categorized into 4 cohorts according to 2nd-line treatments with retesting results: T790M+ patients sequentially treated with osimertinib in cohort A, T790M patients treated with chemotherapy or other treatments in cohort B, and patients with unknown mutation status in cohort C. Cohort D included patients who were still ongoing with afatinib. Primary outcome was the time on treatment (TOT) of patients receiving 1st-line afatinib (TOT-1) followed by 2nd-line treatments (TOT-2). Secondary endpoints were acquisition rate of T790M after progression, objective response rates of afatinib (ORR-1) and 2nd-line treatments (ORR-2), and overall survival (OS). Results: Among a total of 761 enrolled patients, 737 patients excluding 24 screening failures were allocated into cohort A (n=116), B (n=143), C (n=111), and D (n=367). Median age was 62 years (22 - 90) with 53.05% of female proportion. Brain metastasis was discovered in 38.94% at initial diagnosis. Regarding genotypes of EGFR mutations, del19 was 57.53%, 31.48% for L858R, 7.33% for uncommon mutations, and 3.66% for compound mutation. Median TOTs in cohort A, B, C, and D were 35.09 months (95% CI, 30.09 to 43.53), 18.76 months (95% CI, 16.92 to 20.20), 12.02 months (95% CI, 10.22 to 14.98), and 42.61 months (95% CI, 30.95 to 59.23), respectively. Particularly, in cohort A, median TOT-1 and TOT-2 were 17.43 months (95% CI, 15.21 to 19.32) and 11.04 months (95% CI, 7.10 to 14.13), respectively. Retesting was attempted in 262 of 370 patients (70.81%) with 44.27% of T790M detection rate. ORR-1 and -2 in cohort A, B, and C were 84.48% and 56.03%, 82.52% and 29.08%, 54.95% and 21.70%, respectively and 68.94% of ORR for cohort D. Median OS has was not reached. Conclusions: These data suggest that, in real-world practice, sequential afatinib followed by osimertinib be a feasible and effective therapeutic strategy for EGFR M+ NSCLC patients acquiring T790M during the period of afatinib treatment. Of note, median TOT in cohort D is over 3.5 years, suggesting that 1st-line afatinib potentially allow certain patients to maintain long-term, chemotherapy-free state. Further analysis is currently being undertaken and will be presented.