Data from the phase II PrE0505 multicenter trial showed that adding durvalumab, an immune checkpoint antibody targeting programmed cell death ligand 1 (PD-L1), to the combination of cisplatin and pemetrexed chemotherapy improved outcomes in previously untreated patients with unresectable malignant pleural mesothelioma. Patrick Forde, MBBCh, presented findings from the study during the lung cancer oral abstract session of the ASCO20 Virtual Scientific Program.1
Patrick Forde, MBBCh
Dr. Forde is Associate Professor of Oncology at the Johns Hopkins University School of Medicine, Director of the Kimmel Center’s Thoracic Cancer Clinical Research Program, and a Bloomberg-Kimmel Institute for Cancer Immunotherapy investigator.
Efficacy and Safety
A total of 55 patients with malignant pleural mesothelioma of any histologic subtype [epithelioid (75%); biphasic (11%); sarcomatoid (13%); and desmoplastic (2%)] from 15 cancer centers in the United States participated in the study. Eligible patients received durvalumab at a dose of 1,120 mg intravenously on day 1 of each 21-day cycle for up to 6 cycles. This was followed by intravenous administration of pemetrexed at 500 mg/m2 and cisplatin at 75 mg/m2. Substitution of carboplatin (AUC 5) for cisplatin was permitted if toxicity occurred during the initial treatment.
After up to six cycles of concurrent chemotherapy with durvalumab, patients who had a partial response or stable disease could continue on durvalumab (1,120 mg intravenously) on day 1 of each 21-day cycle.The maximum duration of durvalumab treatment was 12 months from the start of therapy.
The study met its primary endpoint, with a median overall survival of 20.4 months (one-sided P = .0014) compared with 12.1 months for historical controls.2 Overall survival rates at 12 and 24 months were 70.4% and 44.2%, respectively.
Investigators reported that the treatment was well tolerated overall, with no unexpected side effects observed.
“Durvalumab plus standard chemotherapy delivered a promising median overall survival rate for patients with previously untreated, inoperable malignant pleural mesothelioma,” said Dr. Forde.
Study Rationale
Inoperable malignant pleural mesothelioma is a rare and aggressive cancer of the pleura, often caused by exposure to asbestos. Dr. Forde reported that “inflammation is key to the development of pleural mesothelioma, and as such, it represents a key target for immunotherapy. This, in addition to earlier studies, showed promising results using the same immunotherapy in previously treated cases and led us to study the combination.”
Tissue Samples Studied
The researchers studied tissue samples from patients who received the combination therapy and found it prevented the protein PD-L1 from forming a “protective armor” around cancer cells. Durvalumab acts against PD-L1 and thus disrupts a cancer cell’s ability to avoid detection and destruction by immune cells.
“Because of the promising results, we are in the process of starting a phase III study to confirm the benefit of this approach,” Dr. Forde said. This study will begin accruing patients across the United States and Australia in late 2020.
DISCLOSURE: Dr. Forde has served as a consultant or advisor to AbbVie, AstraZeneca/MedImmune, Bristol-Myers Squibb, and Janssen Pharmaceuticals and has received institutional research funding from AstraZeneca/MedImmune, Bristol-Myers Squibb, Corvus Pharmaceuticals, Kyow Hakko Kirin, and Novartis. For full disclosures of all study authors, visit coi.asco.org.
REFERENCES
1. Forde P, Sun Z, Anagnostou V, et al: PrE0505: Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma—A PrECOG LLC study. ASCO20 Virtual Scientific Program. Abstract 9003.
2. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al: Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21:2636-2644, 2003.
