Addition of Berzosertib to Topotecan Did Not Improve PFS Among Patients With Relapsed Small Cell Lung Cancer

According to results from a phase 2 study, the addition of berzosertib to topotecan significantly improved overall survival (OS) but did not improve progression-free survival (PFS) among patients with relapsed small cell lung cancer (SCLC). 

“Patients with relapsed SCLC, a high replication stress tumor, have poor prognoses and few therapeutic options,” stated Nobuyuki Takahashi, MD, National Cancer Institute, Center for Cancer Research, Bethesda, Maryland, and coauthors. “A phase 2 study showed antitumor activity with the addition of the ataxia telangiectasia and Rad3-related kinase inhibitor berzosertib to topotecan.”

In this open-label study, 60 patients with SCLC who relapsed after 1 or more prior therapies were randomized based on sensitivity to first-line platinum-based chemotherapy to receive either 1.25 mg/m² of intravenous topotecan plus 210 mg/m² of intravenous berzosertib on days 2 and 5 of a 21-day cycle (n = 40), or topotecan alone on days 1 through 5 (n = 20). The primary end point was PFS in the intention-to-treat population. The secondary end point was OS in the overall population, and among patients with platinum-sensitive or platinum-resistant tumors. 

At a median follow-up of 21.3 months, PFS was 3.9 months in the berzosertib arm and 3 months in control arm (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.46 to 1.41; P = .44). OS was 8.9 months in the berzosertib arm and 5.4 months in the control arm (HR, 0.53; 95% CI, 0.29 to 0.96, P = .03). Patients in both treatment groups experienced similar adverse events which included grade 3 or 4 thrombocytopenia and any grade of nausea. 

“In this randomized clinical trial, treatment with berzosertib plus topotecan did not improve PFS compared with topotecan therapy alone among patients with relapsed SCLC. However, the combination treatment significantly improved OS,” concluded Dr Takahashi and coauthors. 

Source: 

Takahashi N, Hao Z, Villaruz LC, et al. Berzosertib plus topotecan vs topotecan alone in patients with relapsed small cell lung cancer. JAMA Oncol. Published online October 12, 2023. doi:10.1001/jamaoncol.2023.4025