Durvalumab Plus Chemotherapy Doubles Median Survival to 20 Months in Mesothelioma Trial

Adding the immunotherapy drug durvalumab to standard chemotherapy nearly doubled median survival in people with unresectable pleural mesothelioma, according to results from the PrE0505 Phase II trial. Median overall survival reached 20.4 months, compared to 12.1 months in a historical control group treated with chemotherapy alone.

The trial, led by Dr. Patrick Forde at Johns Hopkins, enrolled 55 people across 15 US sites between June 2017 and June 2018. Results were presented at the ASCO 2020 annual meeting.

Trial Design and Results

Participants received up to six cycles of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) or carboplatin (AUC 5) combined with durvalumab (1,120 to 1,500 mg) every three weeks. Those who responded continued on durvalumab maintenance therapy for up to 12 months.

The trial met its primary endpoint with statistical significance (one-sided P = .0014). At 12 months, 70.4% of participants were alive. At 24 months, that figure was 44.2%.

Among secondary endpoints, the six-month progression-free survival rate was 69.1%. The objective response rate reached 56.4%, with 31 of 55 participants achieving partial responses. Another 22 had stable disease. Only one participant experienced disease progression during treatment.

The combination was well-tolerated. Most durvalumab-related adverse events were grade 1 or 2, and no unexpected toxicities emerged.

What Durvalumab Adds

Durvalumab is a PD-L1 immune checkpoint inhibitor. It works by blocking a protein that cancer cells use to hide from the immune system. By removing this shield, durvalumab helps the body’s own immune cells recognize and attack the tumor.

Standard first-line chemotherapy for pleural mesothelioma (pemetrexed plus a platinum drug) has been the backbone of treatment since 2004, when it was shown to extend median survival to about 12 months. The PrE0505 results suggest that adding immunotherapy to this regimen could meaningfully extend that timeline.

The combination of ipilimumab and nivolumab (another immunotherapy approach) received FDA approval for mesothelioma in 2020, with a reported median overall survival of 18.1 months in the CheckMate 743 trial. The PrE0505 durvalumab-chemotherapy combination’s 20.4-month median survival compares favorably, though direct comparisons across different trials are limited.

The Phase III DREAM3R Trial

A confirmatory Phase III trial, DREAM3R (NCT04334759), is testing durvalumab plus chemotherapy against standard care in a randomized setting. The trial uses 1:1 randomization, with the experimental arm receiving durvalumab (1,500 mg every three weeks) combined with four to six cycles of chemotherapy, followed by durvalumab maintenance every four weeks.

Early data from DREAM3R showed improvements in overall survival, progression-free survival, and response rates, but the results have not yet reached statistical significance. Full data maturation is ongoing.

Context for People with Mesothelioma

These results add to a growing body of evidence supporting immunotherapy combinations as first-line treatment for pleural mesothelioma. The PrE0505 data is particularly relevant for people whose disease cannot be surgically removed, as the entire study population had unresectable tumors.

No predictive biomarkers, such as PD-L1 expression levels, were identified that could predict which individuals would benefit most. Research into T-cell responses and other potential markers from the PrE0505 cohort is ongoing.