More than half of the mesothelioma patients who received a combination of Bristol-Myers Squibb‘s checkpoint blockers Opdivo (nivolumab) and Yervoy (ipilimumab) lived a year or more after treatment, according to the latest results of a Phase 2 clinical trial.
Researchers presented the findings on the malignant pleural mesothelioma combo at the European Society for Medical Oncology (ESMO) Congress in Madrid, Sept. 8-12.
The combination, tested in the MAPS2 trial (NCT02716272), represents a new approach to cancer immunotherapy that might hold back the progression of the aggressive cancer better than approaches used so far.
MAPS2 involved 125 patients whose cancer progressed after one or two courses of Eli Lilly’s Alimta (pemetrexed) and platinum chemotherapy. The Alimta-platinum combo is the standard approach to mesothelioma treatment, and is sometimes combined with Genentech’s blood vessel growth blocker Avastin (bevacizumab).
Participants were randomly assigned treatment with Opdivo alone or a combination of Opdivo and Yervoy. While both drugs are checkpoint inhibitors, they target different checkpoint molecules. Opdivo blocks PD-L1 while Yervoy prevents the actions of CTLA-4.
Data released in June 2017 showed that the combination controlled disease — by either shrinking tumors or preventing them from growing — in 50 percent of patients at 12 weeks. The disease control rate in people treated with Opdivo alone was 44 percent.
At one year, 51 percent in the Opdivo group were still alive. In the combination group, the overall survival was 58 percent.
Researchers followed the patients for a median of 15 months. The overall survival rate was 13.6 months in the Opdivo group. Meanwhile, median overall survival was not reached in the combination group — meaning that more than half of Opdivo plus Yervoy-treated patients were still alive.
Researchers at the Intergroupe Francophone de Cancerologie Thoracique (IFCT) — who conducted the trial — also reported that there were no unexpected side effects of the treatment. IFCT is a research organization specializing in lung cancer.
“These overall survival results for second- or third-line treatment of mesothelioma are impressive and comparable with the results of standard chemotherapy in the first line setting,” Gérard Zalcman, head of the IFCT’s Thoracic Oncology Department, said in a press release. “The fact that the median overall survival has not been reached in the combination arm suggests that it would be more than 15 months,” added Zalcman, an IFCT past resident who was the study’s lead author.
The combination also increased the time it took for patients’ mesothelioma to progress — from four months with Opdivo to 5.6 months with both Opdivo and Yervoy.
“These overall survival and progression-free survival results support a recent decision by the U.S. Food and Drug Administration to grant orphan drug status to the combination therapy for mesothelioma,” said Zalcman, who is also a professor at the Bichat-Claude Bernard Hospital and Paris Diderot University in France.
Researchers also discovered that only 41 percent of patients had the PD-L1 molecule in their tumor and that only three had PD-L1 in more than half of their tumor cells. Neither progression-free nor overall survival was, however, linked to the amount of PD-L1 found, researchers said
“In lung cancer, a high mutation burden and a strong PD-L1 expression have been associated with a better response to immune checkpoint inhibition. In mesothelioma the tumor mutation burden is low and the expression of PD-L1 is less prominent; however, there is often an immune cell infiltrate and an inflamed state which suggests it may respond to treatment,” said Rolf Stahel, chair of the Cancer Centre Zürich in Switzerland, who commented on the finding on behalf of ESMO.
But Stahel pointed out that far from all patients appeared to benefit from the treatment.
“This trial found an objective response rate of 18–27% with a PD-1 inhibitor alone or a PD-1 inhibitor and CTLA-4 inhibitor combined. This is a similar range to that found in several other solid tumors with a higher mutation burden, which is good news. However, it appears to be promising in just a fraction of these patients.” Objective response refers to the number of patients who achieve either a full or partial response to a treatment.
The results indicate that more studies of immunotherapy approaches in mesothelioma are needed, Stahel said.
In addition to this IFCT-sponsored trial, Bristol-Myers Squibb is conducting a trial of the combination in pleural mesothelioma.