Fennell, Dean A, Ewings, Sean, Ottensmeier, Christian 
ORCID: 0000-0003-3619-1657, Califano, Raffaele, Hanna, Gerard G, Hill, Kayleigh, Danson, Sarah, Steele, Nicola, Nye, Mavis, Johnson, Lucy et al (show 11 more authors)
(2021)
Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial.
LANCET ONCOLOGY, 22 (11).
pp. 1530-1540.
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Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM) a multicentre, double-blind, randomised,.pdf - Published version Download (617kB) | Preview |
Abstract
<h4>Background</h4>No phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients.<h4>Methods</h4>This was a multicentre, placebo-controlled, double-blind, parallel group, randomised, phase 3 trial done in 24 hospitals in the UK. Adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed pleural or peritoneal mesothelioma, who had received previous first-line platinum-based chemotherapy and had radiological evidence of disease progression, were randomly assigned (2:1) to receive nivolumab at a flat dose of 240 mg every 2 weeks over 30 min intravenously or placebo until disease progression or a maximum of 12 months. The randomisation sequence was generated within an interactive web response system (Alea); patients were stratified according to epithelioid versus non-epithelioid histology and were assigned in random block sizes of 3 and 6. Participants and treating clinicians were masked to group allocation. The co-primary endpoints were investigator-assessed progression-free survival and overall survival, analysed according to the treatment policy estimand (an equivalent of the intention-to-treat principle). All patients who were randomly assigned were included in the safety population, reported according to group allocation. This trial is registered with Clinicaltrials.gov, NCT03063450.<h4>Findings</h4>Between May 10, 2017, and March 30, 2020, 332 patients were recruited, of whom 221 (67%) were randomly assigned to the nivolumab group and 111 (33%) were assigned to the placebo group). Median follow-up was 11·6 months (IQR 7·2-16·8). Median progression-free survival was 3·0 months (95% CI 2·8-4·1) in the nivolumab group versus 1·8 months (1·4-2·6) in the placebo group (adjusted hazard ratio [HR] 0·67 [95% CI 0·53-0·85; p=0·0012). Median overall survival was 10·2 months (95% CI 8·5-12·1) in the nivolumab group versus 6·9 months (5·0-8·0) in the placebo group (adjusted HR 0·69 [95% CI 0·52-0·91]; p=0·0090). The most frequently reported grade 3 or worse treatment-related adverse events were diarrhoea (six [3%] of 221 in the nivolumab group vs two [2%] of 111 in the placebo group) and infusion-related reaction (six [3%] vs none). Serious adverse events occurred in 90 (41%) patients in the nivolumab group and 49 (44%) patients in the placebo group. There were no treatment-related deaths in either group.<h4>Interpretation</h4>Nivolumab represents a treatment that might be beneficial to patients with malignant mesothelioma who have progressed on first-line therapy.<h4>Funding</h4>Stand up to Cancer-Cancer Research UK and Bristol Myers Squibb.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CONFIRM trial investigators, Humans, Peritoneal Neoplasms, Pleural Neoplasms, Recurrence, Survival Rate, Double-Blind Method, Aged, Female, Male, Antineoplastic Agents, Immunological, B7-H1 Antigen, Nivolumab, Progression-Free Survival, Mesothelioma, Malignant, Immune Checkpoint Inhibitors |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 22 Dec 2021 09:41 |
| Last Modified: | 18 Jan 2023 21:18 |
| DOI: | 10.1016/S1470-2045(21)00471-X |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3145785 |
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