A low but significant proportion of EGFR-mutant adenocarcinomas transforms to SCLC at the time of acquisition of resistance to EGFR TKI therapy . Moreover, cases of de novo SCLC harbouring EGFR mutations have been reported . As the clinical characteristics and clinical course of SCLC-transformed EGFR-mutant lung cancer are largely unknown, Marcoux et al. retrospectively reviewed the records of 16 patients with EGFR-mutant SCLC treated between 2006 and 2017 . According to this analysis, the tumours maintained their founder EGFR mutation and were mutually exclusive with T790M. This also applied to cases that had previously been T790M-positive. As with de novo SCLC, EGFR-mutant SCLC-transformed tumours frequently harboured mutations in TP53, RB1 and PIK3CA.
Median PFS of the entire cohort for initial therapy after transformation was 3.3 months. Platinum-etoposide was used as the most common regimen directly after SCLC diagnosis. Responses to platinum-based chemotherapy were frequent, but transient. Among all post-transformation treatment lines considered, the first use of a platinum-based regimen showed a clinical response rate of 72 % and a median PFS of 4.6 months. No responses occurred in five patients who received immune checkpoint inhibitors.
Median OS from initial diagnosis of metastatic lung cancer was 38 months, which is similar to the expected OS in patients who do not undergo SCLC transformation. From SCLC transformation onward, median OS was 8.8 months, which is similar to that observed in patients with de novo SCLC. Further investigation is called for to better elucidate optimal diagnostic approaches and treatment strategies for this group of patients.