In epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC), there are various treatment challenges. Most patients develop resistance and relaps within 1-1.5 years after first-line EGFR- tyrosine kinase inhibitor (TKI) treatment [1st- and 2nd- generation (G) TKIs]. Some studies suggest that afatinib may overcome the tumor heterogeneity.
We conducted the multi-center retrospective study in patients with EGFR-mutant NSCLC after acquired resistance to EGFR-TKIs appeared at any line of therapy. The outcomes between afatinib followed by osimertinib and 1st-G EGFR TKIs followed by osimertinib (3rd-G EGFR TKI) were evaluated.
We enrolled 111 T790M mutation-positive patients treated with osimertinib. The median age was 69 (range: 39-88) year old. Among them, 33 (29.7%) were male, 100 (90%) were with PS 0-1, and 35 (31.5%) were treated with afatinib followed by osimertinib. The median treatment line with afatinib or 1st-G EGFR TKI followed by osimertinib was 5 or 4. In all patients, the objective response and disease control rates were 63.1% and 77.5%, respectively. The objective response and disease control rates were significantly higher in patients with afatinib followed by osimertinib than in those with 1st-G EGFR TKI followed by osimertinib [82.9% vs 53.9% (p = 0.0065) and 91.4% vs 71.1% (p = 0.032)], respectively. The median PFS (with <60% events) was longer and in favor of afatinib followed by osimertinib compared with 1st-G EGFR TKI followed by osimertinib (15.7 vs 8.9 months, p = 0.195). The follow-up is still ongoing.
Afatinib followed by osimertinib may provide better clinical benefit for NSCLC patients harboring T790M mutation compared with 1st-G EGFR TKIs. Afatinib followed by osimertinib is one of the first line sequential options even if osimertinib can be used as a first line therapy.
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All authors have declared no conflicts of interest.