Olaparib as maintenance treatment in patients with chemosensitive small cell lung cancer (STOMP): A randomised, double-blind, placebo-controlled phase II trial. (September 2022)

• Record Type: Journal Article
• Authors: Woll, Penella; Gaunt, Piers; Danson, Sarah; Steele, Nicola; Ahmed, Samreen; Mulatero, Clive; Shah, Riyaz; Bhosle, Jaishree; Hodgkinson, Elizabeth; Watkins, Ben; Billingham, Lucinda
• Is Part Of: Lung cancer. Volume 171(2022)
• Page Start: 26
• Page End: 33
• Publication Date: 2022-09
• Subjects: Small cell lung cancer -- Maintenance treatment -- Olaparib -- Clinical trial; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2022.07.007
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: SCLC is highly mutated and over expresses PARP. We tested the efficacy of PARP inhibitor olaparib after first line therapy in SCLC. 220 patients were randomized to receive maintenance olaparib or placebo. Olaparib did not significantly alter progression-free survival or overall survival. Quality of life and performance status were unchanged with the addition of olaparib. Abstract: Objectives: Small cell lung cancer (SCLC) responds well to chemoradiotherapy but frequently relapses. Here, we evaluate activity and safety of the poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitor olaparib as maintenance treatment for patients with chemoresponsive SCLC. Materials and methods: Eligible patients had complete or partial response to first line chemotherapy or chemoradiotherapy for SCLC. Patients were randomised 2:2:1:1 to olaparib 300 mg twice a day (BD), olaparib 200 mg three times a day (TDS), placebo BD or placebo TDS. The primary outcome was progression-free survival time (PFS). The trial design had 80% power to detect a 3-month difference in median PFS based on a one-sided 5% significance level. Secondary outcome measures included overall survival time (OS), adverse events and quality of life. ISRCTN 73164486, EudraCT 2010-021165-76. Results: 220 patients were randomised: 74 placebo, 73 olaparib BD, 73 olaparib TDS. Median PFS (90% confidence interval (CI)) was 2·5 (1·8, 3·7), 3·7 (3·1, 4·6) and 3·6 (2·8, 4·7) months in the placebo, olaparib BD and TDS arms, respectively. There was no significant difference in PFS between olaparib and placebo for either BD (Hazard Ratio (HR) (90%CI) 0·76 (0·57, 1·02), P = 0·125 or TDS 0·86, (0·64, 1·15), P = 0·402. Common adverse events on olaparib were fatigue, nausea, anaemia, vomiting and anorexia. Of 214 patients who discontinued treatment before 24 months, toxicity was the reason cited for 66 (18 placebo, 24 olaparib BD, 24 olaparib TDS). Conclusion: This trial does not provide sufficient evidence that either the BD or TDS regimen for maintenance olaparib monotherapy improves PFS or OS in an unselected SCLC population to warrant further research. Toxicity for olaparib was similar to other studies.