O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with extensive-stage small-cell lung cancer (ES-SCLC): a prospective cohort study

Abstract Purpose To assess the prognostic value of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with etoposide plus platinum chemotherapy. Methods A prospective single arm cohort study was performed in a tertiary teaching hospital in China. The rate of MGMT promoter methylation was detected by quantitative methylation specific PCR (qMS-PCR) assay before etoposide plus platinum chemotherapy. Primary endpoint was tumor response to chemotherapy according to Response Evaluation Criteria in Solid Tumors. Results Between July 2019 and June 2021, 19 untreated patients with ES-SCLC were enrolled. After a median follow-up of 9 months, no patient was complete response (CR), 14 patients were assessed as partial response (PR), 1 patient was stable disease (SD) and 4 patients were progressive disease (PD). Time to progression (TTP) was median 90 days, range 42 to 270 days. The rates of MGMT promoter methylation were more than 40% in all PD patients (N=4), however, less than 40% in all PR or SD patients (N=15). Conclusion A high rate of MGMT promoter methylation may be a predictor of poor response to etoposide plus platinum chemotherapy in patients with ES-SCLC.