Imfinzi-Chemo Combo Improves Survival for Mesothelioma

Imfinzi plus platinum-pemetrexed chemotherapy induced survival improvements in patients with previously untreated, unresectable malignant pleural mesothelioma, compared with chemotherapy alone.

Treatment with Imfinzi (durvalumab) plus platinum-pemetrexed chemotherapy was associated with improved survival among patients with previously untreated, unresectable malignant pleural mesothelioma compared with chemotherapy alone, according to recent study results.

Moreover, the data — which were published in Nature Medicine — demonstrated that subgroups of patients with the rare cancer achieved significant benefit from the combination.

“Historically, the outcomes for mesothelioma have not been good; whether that be with surgery or without surgery,” lead study author Dr. Patrick Forde, director of the Thoracic Oncology Clinical Research Program at Johns Hopkins Medicine in Baltimore, said in an interview with CURE®. “It’s an unusual tumor type in that surgery probably has a modest role to play for most patients. We’re relying more and more on developing new medication treatments such as in this clinical trial, and I think the signals here are that there are groups of patients who derive a significant benefit from the combination of chemo with immunotherapy.”

Developments over the past two decades have been relatively scarce, according to Forde. In fact, he noted that aside from the recent Food and Drug Administration (FDA) approval of Opdivo (nivolumab) plus Yervoy (ipilimumab), little progress has been made in terms of treatment advances.

That was until a few years ago, Forde said.

“We were starting to see some signals of efficacy from chemo-immunotherapy for other cancers (such as) lung cancer (and) for some gastrointestinal cancers,” he said.

Additionally, Forde noted that data were starting to show that the use of single-agent immunotherapies was associated with some type of activity in patients with mesothelioma. That coupled with the fact that epithelioid mesothelioma — which, according to NYU Langone Health, accounts for more than 50% of all mesotheliomas — is susceptible to chemo, made this combination enticing to study, according to Forde.

The phase 2 trial — known as PrE0505 — included 55 patients with previously untreated, unresectable pleural malignant mesothelioma. Measuring overall survival (time that a patient with cancer is still alive) was the main goal of the study. Other goals included assessing the safety of the combination, as well as progression-free survival (the time a patient lives without their disease getting worse).

After a median follow-up of 24.2 months, the median overall survival for the entire patient population was 20.4 months and, as Forde noted, was significantly longer than the 12 months observed in previous studies with chemotherapy. At 24 months, it was estimated that 44.2% of patients were still alive. Moreover, the median progression-free survival (time during and after treatment when the patient lives without disease progression)was 6.7 months.

Although none of the study participants achieved a complete response, 31 patients reached a partial response to treatment. The results also indicated that patients with epithelioid tumors achieved a greater objective response rate (percentage of patients whose disease partially and completely responds to the treatment) than those with non-epithelioid tumors (65.9% vs. 28.6%, respectively).

“There were some signals, particularly for those patients who had epithelioid mesothelioma, that the median survival exceeded two years for those patients in the trial, which is longer than what we've seen in other clinical trials for epithelioid mesothelioma,” he said.

The combination was also tolerable, according to Forde. The most reported side effects of any severity amongst all participants included fatigue (67%), nausea (56%) and anemia (56%). Serious or severe treatment-related side effects were reported in 65.5% of patients.

“The goal of this study was to demonstrate that survival would be longer with this treatment compared to what we would expect with chemotherapy alone. And the goal was to improve the survival by about slightly over 50%. And that was what we showed in the trial,” he concluded.


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