P1.07-015 STOMP: A UK National Cancer Research Network Randomised, Double Blind, Multicentre Phase II Trial of Olaparib as Maintenance Therapy in SCLC: Topic: Drug Treatment Alone and in Combination with Radiotherapy

STOMP (ISRCTN 73164486, CRUK/10/037, EudraCT 2010-021165-76) is a randomized, double-blind, placebo-controlled phase II trial to evaluate activity and safety of the PARP inhibitor olaparib (AstraZeneca) as maintenance treatment for patients with chemo-responsive small cell lung cancer (SCLC). Two schedules of olaparib oral tablets were investigated: 300mg twice daily (bd) or 200mg three times daily (tds). Eligible patients had pathologically confirmed SCLC with response to first line chemotherapy or chemo-radiotherapy. Patients were stratified by metastasis-status and prior radiotherapy and randomized in a 2:2:1:1 ratio to: olaparib tds, olaparib bd, placebo tds or placebo bd. Placebo arms were pooled for analyses. Primary outcome was progression-free survival (PFS). There is 80% power to detect a difference of 3 months in PFS (from 4.8 months) between treatments based on a one-sided 5% significance level. Key secondary outcome measures were overall survival (OS), adverse events (AEs) and quality of life. Between November 2013 and December 2015, 220 UK patients were randomized. Arms were well balanced for stratification factors of prior radiotherapy (89% Yes) and metastasis status (66% M1) as well as sex (46% M) and age (median=64, range 42-89). Median follow-up for 31 event-free patients was 14 months (range 0–24). Median PFS was 2.6 (90% CI 1.8, 3.7), 3.6 (90% CI 3.1, 6.0) and 3.6 (90%CI 3.1, 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 the bd (Cox-Adjusted HR 0.87; 90% CI 0.64, 1.18; stratified logrank p=0.29) or the tds arm (0.89; 90% CI 0.67, 1.20; p=0.43). Median OS was 8.9 (90% CI 7.0, 11.9), 9.9 (90% CI 7.6, 12.9) and 9.0 (90% CI 6.6, 11.8) months in the placebo, olaparib bd and tds arms, respectively. There was no significant difference in OS between olaparib and placebo for either the bd (Cox-Adjusted HR 0.97; 90% CI 0.69, 1.37; stratified logrank p=0.73) or the tds arm (1.05; 90% CI 0.76, 1.46; p=0.73). The most common AEs on olaparib were fatigue, nausea, anemia, vomiting and anorexia. 68 patients discontinued treatment citing AEs (17 placebo, 26 olaparib bd, 25 olaparib tds). There is no evidence that either the bd or tds regimen for olaparib improves PFS or OS in an unselected population. The AE profile for olaparib in SCLC is similar to that observed in other studies.