A chemotherapy-free combination significantly improved overall survival (OS) as initial therapy for unresectable malignant pleural mesothelioma (MPM), a large randomized trial showed.
Patients treated with nivolumab (Opdivo) and ipilimumab (Yervoy) had a media OS of 18.1 months versus 14.1 months for patients randomized to chemotherapy. The combination performed equally well in epithelioid and non-epithelioid tumors, whereas chemotherapy performed as expected in epithelioid disease but substantially worse in the subgroup of patients with non-epithelioid disease, who lived more than twice as long with immunotherapy.
An exploratory analysis suggested that nivolumab and ipilimumab performed substantially better in PD-L1-positive tumors, which accounted for a majority of the study population, reported Paul Baas, MD, of the Netherlands Cancer Institute in Amsterdam, reported at the World Conference on Lung Cancer (WCLC) virtual meeting.
“The survival benefit with nivolumab and ipilimumab was observed regardless of histology, while chemotherapy performed better in epithelioid histology, as expected,” said Baas. “The PD-L1 data are descriptive in nature and preclude firm conclusions. This is the first positive randomized trial of dual immunotherapy in the first-line treatment of patients with mesothelioma. Therefore, nivolumab and ipilimumab should be considered as a new standard of care.”
Invited WCLC discussant Dean A. Fennell, MD, of the University of Leicester in England, called the results “transformative” and agreed with Baas’ assessment that the combination of nivolumab and ipilimumab “heralds a new standard of care in this setting.”
“Non-epithelioid histology exhibited marked chemoresistance, potentially associated with epithelioid mesenchymal transition, but was not positively predictive,” said Fennell. “Looking forward, chemoimmunotherapy or selective targeting of non-epithelioid mesothelioma could further extend the benefit for patients with ipilimumab and nivolumab.”
Prognosis for unresectable MPM remains poor, associated with a 5-year OS of less than 10%. Platinum-based combination chemotherapy has been the standard of care for more than 15 years, Baas noted.
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