Adding durvalumab to first-line pemetrexed and cisplatin improved survival in patients with unresectable malignant pleural mesothelioma (MPM) in a phase 2 trial, compared with historical controls who received only pemetrexed and cisplatin.
The median overall survival was 20.4 months in patients who received durvalumab plus pemetrexed-cisplatin. This is significantly longer than the median overall survival of 12.1 months (P = .0014) observed with pemetrexed-cisplatin in a prior phase 3 study (J Clin Oncol. 2003 Jul 15;21[14]:2636-44).
The new phase 2 results are “promising,” said lead investigator Patrick Forde, MBBCh, director of the thoracic cancer clinical research program at Johns Hopkins University in Baltimore.
He presented the results as part of the American Society of Clinical Oncology virtual scientific program.
Dr. Forde noted that a phase 3 trial directly comparing pemetrexed-cisplatin plus durvalumab to pemetrexed-cisplatin will begin recruiting this year. The trial is a collaboration between U.S. investigators and Australian researchers who reported their own phase 2 results with durvalumab plus pemetrexed-cisplatin in 2018 (J Thorac Oncol. 2018 Oct;13[10]:S338-339).
Study details
Dr. Forde’s phase 2 study enrolled 55 patients with treatment-naive, unresectable MPM. Their median age was 68 years (range, 35-83 years), and 45 (82%) were men. All had an Eastern Cooperative Oncology Group performance status of 0-1.
Epithelioid mesothelioma was the histologic subtype in three-quarters of patients. “It was a fairly typical mesothelioma population,” Dr. Forde said.
The patients received durvalumab at 1,120 mg plus pemetrexed at 500 mg/m2 and cisplatin at 75 mg/m2 every 3 weeks for up to six cycles. Carboplatin was substituted when cisplatin was contraindicated or patients developed toxicities.
All but one patient had stable or responding disease on radiography and went on to durvalumab maintenance, also given at 1,120 mg every 3 weeks, for up to 1 year from study entry.
Results
Dr. Forde said this study had 90% power to detect a 58% improvement in median overall survival, from the 12.1 months seen in historical controls to 19 months, which was the goal of this study.
It was a positive study, he said, as the median overall survival was 20.4 months (P = .0014).
The overall survival rate was 87.2% at 6 months, 70.4% at 12 months, and 44.2% at 24 months. The progression-free survival rate was 69.1% at 6 months, 16.4% at 12 months, and 10.9% at 24 months.
The overall response rate was 56.4%, which comprised 31 partial responses. Forty percent of patients (n = 22) had stable disease. One patient had progressive disease, and one was not evaluable (1.8% each).
To help with future patient selection, the researchers looked for baseline biomarkers that predicted response. Tumor PD-L1 expression, tumor mutation burden, and other potential candidates haven’t worked out so far, but the work continues, Dr. Forde said.
He noted that many of the adverse events in this trial are those typically seen with platinum-based chemotherapy.
Grade 3/4 treatment-emergent adverse events included anemia (n = 14), fatigue (n = 4), decreased appetite (n = 1), and hypomagnesemia (n = 1).
The most common grade 1/2 adverse events of special interest were hypothyroidism (n = 7), rash (n = 5), pruritus (n = 3), AST elevation (n = 3), and hyperthyroidism (n = 3).