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.
| Original language | English |
|---|---|
| Pages (from-to) | 26-33 |
| Number of pages | 8 |
| Journal | Lung Cancer |
| Volume | 171 |
| Early online date | 15 Jul 2022 |
| DOIs | |
| Publication status | Published - Sept 2022 |
Bibliographical note
Funding Information:This work was supported by Cancer Research UK [CRUK/10/037 to P.W.] and AstraZeneca [ISS22810017 to P.W.]. This trial was an investigator-initiated study supported by the collaboration between AstraZeneca and the UK National Cancer Research Network, for which AstraZeneca provided partial funding. This study was sponsored by Sheffield Teaching Hospitals NHS Foundation Trust (ISS22810017) and run by the Cancer Research UK Clinical Trials Unit, University of Birmingham. Staff at the CRCTU who contributed to the trial were supported by a core funding grant from Cancer Research UK (C22436/A25354).
PJW and LJB conceived the study which they designed with help from PG, SJD and EH. All authors contributed to the acquisition and interpretation of the data, and preparation of the manuscript. All authors approved the final manuscript. The authors are grateful to all the patients who participated in the trial and their families. We also acknowledge the support of all the participating clinicians and their local research teams. We thank all staff at Cancer Research UK Clinical Trials Unit (CRCTU) at University of Birmingham who contributed to this trial, particularly Peter Fletcher for statistical support. S.A. reports honoraria and consulting fees from Amgen, AstraZeneca, BMS, Lilly, MSD, Novartis, Pfizer, Roche and Takeda. C.M. has been an employee of MSD since 2017. L.J.B. reports honoraria from AstraZeneca. All remaining authors have declared no conflicting interests. Participant data and the associated supporting documentation will be available within 6 months after the publication of this manuscript. Details of our data request process is available on the CRCTU website. Only scientifically sound proposals from appropriately qualified research groups will be considered for data sharing. The decision to release data will be made by the CRCTU Director's Committee, who will consider the scientific validity of the request, the qualifications and resources of the research group, the views of the Chief Investigator, the trial steering committee, the Sponsor, consent arrangements, the practicality of anonymising the requested data and contractual obligations. A data sharing agreement will cover the terms and conditions of the release of trial data and will include publication requirements, authorship and acknowledgements and obligations for the responsible use of data. An anonymised encrypted dataset will be transferred directly using a secure method and in accordance with the University of Birmingham's IT guidance on encryption of data sets. This work was supported by Cancer Research UK [CRUK/10/037 to P.W.] and AstraZeneca [ISS22810017 to P.W.]. This trial was an investigator-initiated study supported by the collaboration between AstraZeneca and the UK National Cancer Research Network, for which AstraZeneca provided partial funding. This study was sponsored by Sheffield Teaching Hospitals NHS Foundation Trust (ISS22810017) and run by the Cancer Research UK Clinical Trials Unit, University of Birmingham. Staff at the CRCTU who contributed to the trial were supported by a core funding grant from Cancer Research UK (C22436/A25354). The funder had no role in trial design, data collection, data analysis, data interpretation or writing of the report. The chief investigator and corresponding author had full access to all the data in the trial and had final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2022 The Authors
Keywords
- Clinical trial
- Maintenance treatment
- Olaparib
- Small cell lung cancer
ASJC Scopus subject areas
- Oncology
- Pulmonary and Respiratory Medicine
- Cancer Research
