Subsequent therapies post-afatinib among patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC in LUX-Lung (LL) 3, 6 and 7

Abstract

Background: Acquired resistance after front‐line treatment (tx) with 1st‐/2nd‐generation EGFR TKIs necessitates further therapies for pts with EGFRm+ NSCLC. We explored the outcome of subsequent therapies, including other EGFR TKIs and chemotherapy (CT) after 1st‐line afatinib in the LL3, 6 and 7 randomised trials. Methods: We retrospectively assessed subsequent therapy outcomes in pts with common EGFR mutations, who were randomised to 1st‐line afatinib in the LL3/6/7 trials. Data had been prospectively collected as study follow‐up information. Tx duration was assessed by descriptive medians or KMestimates. Biopsies at afatinib resistance were not required in LL3/6/7. Results: Of the 553 pts with common EGFR mutations who received 1st‐line afatinib and later discontinued it, 2nd‐line therapy was given in 394 (71%) pts and consisted of platinum‐based CT for 252 (46%), single agent CT for 39 (7%), 1st‐generation EGFR TKI for 49 (9%) and other tx for 54 (10%) pts. Median time on 2nd‐line tx was 2.9 months for platinum‐based and 1.4 months for single‐agent CT, with no relevant difference between Del19 and L858R mutation subgroups. Among 186 (34%) pts who received 1st‐generation EGFR TKIs post‐afatinib, median time on tx was 3.9 months. Of 212 pts randomised to 1st‐line CT in LL3 and LL6, 117 (55%) received 1st‐generation EGFR TKI monotherapy as 2nd‐line tx, with a median time on tx of 11.2 months. Interestingly, 34 pts received osimertinib after 1st‐line afatinib, the majority in ≥3rd line; median time on osimertinib tx was 31.5 months (95% CI 16.8‐31.5 months). Median OS for osimertinib‐treated pts is not yet evaluable. Conclusions: The majority (71%) of pts who received 1st‐line afatinib were fit enough to receive subsequent therapies and there was no relevant difference in 2nd‐line tx duration by Del19/L858R EGFR mutation subgroup. Introduction of a different TKI was common, with good outcome. Time on tx with osimertinib after afatinib was unexpectedly long among 34 pts; this should be examined in a larger cohort. Overall, these findings suggest that pts treated with 1st‐line afatinib are well suited for subsequent therapies, including CT, 1st‐generation EGFR TKIs and osimertinib.