In patients with relapsed malignant mesothelioma, treatment with single-agent nivolumab led to a significant improvement in both overall and progression-free survival in the phase III CONFIRM trial. These findings were presented by Dean A. Fennell, FRCP, PhD, Professor and Chair of Thoracic Medical Oncology, University of Leicester and University Hospitals of Leicester NHS Trust in the United Kingdom at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC) Singapore, which was moved to a virtual format and held January 28–31, 2021, in light of the COVID-19 pandemic (PS01.11).
“CONFIRM met its co-primary endpoints of improved overall survival and progression-free survival with nivolumab vs placebo in relapsed malignant mesothelioma. Nivolumab monotherapy is a safe and effective treatment and should be considered a new treatment option,” said Dr. Fennell.
Dean A. Fennell, FRCP, PhD
Overall survival data were immature but already significantly longer with nivolumab: a median of 9.2 months vs 6.6 months with placebo (hazard ratio [HR] = 0.72, P = .018). Investigator-assessed progression-free survival was also longer for patients treated with nivolumab vs placebo: a median of 3.0 vs 1.8 months (HR = 0.61, P < .001), Dr. Fennell reported.
CONFIRM is the first ever placebo-controlled phase III trial of an agent targeting PD-1 in relapsed mesothelioma, and the first trial to show an improvement in overall survival following the standard first-line doublet of pemetrexed and cisplatin or carboplatin, he said.
CONFIRM Trial Details
The investigator-led, placebo-controlled randomized phase III CONFIRM (Checkpoint Blockade for Inhibition of Relapsed Mesothelioma) trial involved 24 centers in the United Kingdom. It enrolled 332 patients with previously treated, unresectable mesothelioma (pleural or peritoneal), randomly assigning them to receive nivolumab at 240 mg on day 1 of each 14-day cycle (n = 221) or placebo (n = 111). Participants were stratified by epithelioid vs nonepithelioid histology. The co-primary endpoints were investigator-assessed progression-free survival and overall survival.
“The Data Monitoring and Ethics Committee and Trial Steering Committee recommended early release of the results in August 2020,” said Dr. Fennell. Follow-up will continue until July 2021.
At 12 months, the overall survival rate for the nivolumab vs placebo arms was 39.5% and 26.9%, respectively, and the progression-free survival rate was 14.5% vs 4.9%, respectively.
A significant clinical benefit was observed in patients with the epithelioid subtype (HR = 0.71, P = .021) but not the no-epithelioid subtype (HR = 0.79, P = .572), which Dr. Fennell said could be due to the small number of patients (n = 39) in the latter cohort.
PD-L1 expression was assessed in 234 tumor blocks using the Dako 22C3 tumor proportion score (TPS), and 34% of patients were found to have PD-L1 TPS ≥ 1%. Investigators found no association between this level of expression and overall survival. Hazard ratios for overall survival were 0.95 (P = .864) in the PD-L1–positive cohort and 0.74 (P = .115) in the PD-L1–negative cohort.
Giorgio Scagliotti, MD
Grade 3–4 adverse events were reported in 45% of patients in the nivolumab arm and 42% of patients in the placebo arm; serious adverse events were observed in 36% and 39%, respectively. Deaths related to a serious adverse event were recorded for 3.6% and 5.3%, respectively.
“Therapeutic alternatives are always welcome in the context of a difficult-to-treat disease such as malignant pleural mesothelioma,” said Giorgio Scagliotti, MD, interim IASLC Chief Scientific Officer. “This study contributes to increase our range of treatment opportunities in the setting of relapsed/recurrent disease.”
Disclosure: For full disclosures of the study authors, visit wclc2020.iaslc.org/disclosures.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.