The CONFIRM trial involved 330 previously treated patients with mesothelioma who were randomly assigned to nivolumab or placebo for 1 year or until progression or unacceptable toxicity.
Although recruitment to the study was stopped early because of the COVID-19 pandemic, enough data accrued to show that nivolumab improved overall survival by 28% over placebo, and increased PFS by 39%.
“Nivolumab was deemed a safe and effective treatment and should be considered a new treatment option for patients with relapsed mesothelioma,” said principal investigator Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester (England).
He presented the results at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.
Rina Hui, MD, PhD, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, who was not involved in the study, said that these results had been a “long time coming.”
CONFIRM has added “important, encouraging data on immunotherapy in the salvage setting,” Dr. Hui said, noting that two-thirds of patients had received two or more prior lines of therapy.
Dr. Fennel noted that “a significant clinical benefit was observed in the epithelioid subtype” of the disease but not in patients with nonepithelioid disease.
However, there was “no evidence” to support programmed death–ligand 1 (PD-L1) expression as predictive of outcomes, he added, which does appear to be the case in some trials on lung cancer and other tumors.
Commenting on these observations, Dr. Hui said that PD-L1 as a predictive biomarker in mesothelioma has been “controversial,” and she emphasized that the results from CONFIRM indicate “no evidence of PD-L1 being predictive.”
However, Dr. Hui questioned the other observation that clinical benefit appeared to be seen only in the epithelioid subtype.
She emphasized that nonepithelioid disease is known to be a “more aggressive, chemoresistant subtype ... with a steep decline in the survival curves.
“Therefore, a lot of patients would not have made it to a subsequent-line clinical trial, explaining why there were only 12% in the CONFIRM study,” and so the sample size may be “too small to detect a difference in outcome,” Dr. Hui said.
Consequently, Dr. Hui said she “would not deny patients with nonepithelioid histology from considering nivolumab in the salvage setting.”
She argued that there was “no clear predictive biomarker for patient selection” emerging from the CONFIRM data.
She agreed that, in patients with mesothelioma who have progressed following platinum/pemetrexed-based chemotherapy as in the first line, “monotherapy nivolumab now can be considered as a treatment option in the second- ... or third-line setting, after second-line chemotherapy”.
However, outstanding questions remain, including whether nivolumab “provides better outcomes than second-line single agent chemotherapy or second-line gemcitabine with the [vascular endothelial growth factor receptor] inhibitor ramucirumab.”
It may also be that nivolumab plus ipilimumab might be superior to nivolumab alone in the salvage setting.
But a more fundamental question is what should be considered for salvage therapy if nivolumab and ipilimumab have already been used in the first-line setting, Dr. Hui said.
Results of first-line immunotherapy combination trials are “eagerly awaited ... to determine and develop other salvage treatments,” she commented.
Responding on Twitter, Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust in Royal Tunbridge Wells, England, echoed these comments, saying that the results were “very exciting,” but he also “can’t wait to see the first-line chemo–immunotherapy data.”
Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, commented on Twitter that there was “not a lot of safety data” in the presentation and awaits their eventual publication.
He added that it is “good to have a positive trial” in relapsed mesothelioma, “though the first-line studies will decrease the eventual impact as immunotherapy becomes involved earlier in treatment.”