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 invariably develops following frontline EGFR TKI treatment, and necessitates subsequent therapies for patients with EGFRm+ NSCLC. However, limited clinical data are available to help guide treatment decisions regarding sequential therapy. Here we evaluated the outcomes of subsequent therapies, including other EGFR TKIs and chemotherapy, after first‐line afatinib or chemotherapy in the LUX‐Lung (LL) 3, 6 and 7 randomized trials. Methods: We retrospectively assessed subsequent therapy outcomes in patients with common EGFR mutations, who were randomized to first‐line afatinib or chemotherapy in LL3, 6 and 7. Data were prospectively collected as study follow‐up information. Treatment duration was assessed by descriptive medians or KaplaneMeier estimates. Biopsies at afatinib discontinuation were not required. Results: Of the 553 patients with common EGFR mutations who received first‐line afatinib and later discontinued it, 394 (71%) received second‐line treatment, consisting of platinum‐based chemotherapy in 252/553 (46%), first‐generation EGFR TKI monotherapy in 49/553 (9%), singleagent chemotherapy in 39/553 (7%), and other treatments (including osimertinib) in 54/553 (10%) patients. Median time on second‐line treatment was 2.9 months (i.e. ∼4 cycles) for platinum‐based and 1.4 months for single‐agent chemotherapy, with no relevant difference between Del19 and L858R EGFR mutation subgroups. Among 186 (34%) patients who received subsequent first‐generation EGFR TKI monotherapy, median time on treatment in any line was 3.9 months. Of 212 patients randomized to first‐line chemotherapy in LL3 and LL6, 117 (55%) received first‐generation EGFR TKI monotherapy in second‐line, with a median time on treatment of 11.2 months. Notably, 34 patients received osimertinib after first‐line afatinib, the majority in third or later lines; median time on osimertinib treatment was 31.5 months (95% CI 16.8e31.5 months); median OS for these patients is not yet evaluable. Conclusion: The majority of patients (71%) who received first‐line afatinib in LL3, 6 and 7 received subsequent therapies, with no relevant difference in second‐line treatment duration by Del19/L858R mutation subgroup. Treatment with a first‐generation TKI was common, with good outcome. Time on osimertinib treatment after first‐line afatinib was unexpectedly long among 34 patients, which warrants further examination. Overall, these findings support treatment sequencing with firstline afatinib followed by subsequent therapies, including osimertinib.