Nivolumab prolongs PFS, OS in relapsed malignant mesothelioma
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Nivolumab significantly prolonged PFS and OS compared with placebo for patients with relapsed malignant mesothelioma, according to findings presented at International Association for the Study of Lung Cancer World Conference on Lung Cancer.
“Mesothelioma is predominately a disease that is not suitable for surgery and is one for which chemotherapy has been the standard of care since 2003,” Dean A. Fennell, FRCP, PhD, chair of thoracic medical oncology at University of Leicester and University Hospitals of Leicester NHS Trust in the U.K., said during his presentation. “Patients with relapsed malignant mesothelioma do not have a standard of care. We have not seen an effective treatment in the relapsed setting, despite a number of positive findings in the first-line setting.”
In the placebo-controlled, phase 3 CONFIRM trial, Fennell and colleagues evaluated the efficacy of nivolumab (Opdivo, Bristol Myers Squibb), a PD-1 inhibitor, among a cohort of patients with relapsed mesothelioma.
“The target sample size of the study was 336 patients, but the study was halted due to COVID-19. However, there was sufficient follow-up for us to be able to complete the study,” Fennell said.
Researchers randomly assigned 332 patients who had received at least one prior line of therapy to a 14-day cycle of 240 mg nivolumab (n = 221; median age, 70 years; 76% men) or placebo (n = 111; median age, 71 years; 77% men).
OS and investigator-reported PFS served as co-primary outcomes. PFS as determined by RECIST criteria, response rate and safety served as secondary outcomes.
Baseline characteristics appeared well-balanced between the two groups, although the nivolumab group had a slightly higher percentage of patients with a PD-L1 tumor proportion score (TPS) of 1% or greater (37% vs. 29%), according to Fennell.
Median duration of treatment was 84 days with nivolumab vs. 43 days with placebo. Of note, 1.4% of patients assigned nivolumab received additional immunotherapy compared with 12.6% assigned placebo.
Median follow-up was 17.1 months with nivolumab and 14.2 months with placebo.
According to study results, nivolumab significantly prolonged OS (HR = 0.72; 95% CI, 0.55-0.94), with median OS of 9.2 months (95% CI, 7.5-10.8) vs. 6.6 months (95% CI, 5-7.5) with placebo and 1-year OS of 39.5% (95% CI, 32.5-46.3) vs. 26.9% (95% CI, 18.2-36.4).
Researchers also reported a PFS benefit with nivolumab (HR = 0.61; 95% CI, 0.48-0.77). Median PFS was 3 months with nivolumab vs. 1.8 months with placebo, and 1-year PFS was 14.5% vs. 4.9%.
Moreover, results showed no significant difference in OS among patients with PD-L1-positive vs. -negative disease, according to Fennell.
“PD-L1 status in this sample size in this study was not predictive or prognostic,” he added.
Nivolumab conferred a significant OS benefit among patients with epithelioid disease (HR = 0.71; 95% CI, 0.53-0.95), but not among those with non-epithelioid disease (HR = 0.79; 95% CI, 0.35-1.79).
Grade 3 adverse events occurred among 45% of patients assigned nivolumab and 42% of patients assigned placebo. Serious adverse events occurred more often in the placebo group (39% vs. 36%) as did deaths related to those events (5.3% vs. 3.6%).
“Nivolumab is a safe and effective treatment and should be considered a new treatment option for patients with relapsed mesothelioma,” Fennell said.
Perspective
Back to TopRina Hui, MBBS, PhD
It has been a long time coming to see a positive randomized phase 3 study with a checkpoint inhibitor in relapsed mesothelioma. Historically, there were very limited data on treatment for relapsed mesothelioma. Therefore, participation in clinical trials is encouraged.
The CONFIRM study adds important and encouraging data on immunotherapy in the salvage setting, in which patients had received two or more lines of prior treatment. There was no clear biomarker for patient selection — neither PD-L1 nor histology. However, I would not deny my patients with non-epithelioid histology from considering nivolumab in the salvage setting.
Much still needs to be learned. As this study was placebo-controlled, the question remains whether nivolumab provides better outcomes than first-line chemotherapy or second-line gemcitabine plus ramucirumab (Cyramza, Eli Lilly). Also, would nivolumab plus ipilimumab (Yervoy, Bristol Myers Squibb) be superior to nivolumab alone in the salvage setting? We need to identify effective predictive biomarkers as we await results from combination studies to determine and develop other salvage treatments.
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Fennell DA, et al. Presidential Symposium. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer (virtual meeting); Jan. 28-31, 2021.
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