P3.03-030 Cisplatin with Pemetrexed or Gemcitabine in Prolonged Infusion for Inoperable Mesothelioma: A Phase II Randomized Trial: Topic: Mesothelioma Clinical

Abstract

In a single-arm Phase II trial on 78 patients with advanced mesothelioma, promising objective response rate (ORR, 50%) and overall survival (OS, median: 17.0 months) after treatment with cisplatin and low-dose gemcitabine in long infusion (C-GILI) were reported (Kovac et al, Anticancer Drugs 23:230-38, 2012). Here we present a randomized Phase II clinical trial, comparing cisplatin/pemetrexed (CP) and C-GILI. Eligible patients had histologically confirmed malignant mesothelioma, were chemonaive, had performance status (PS) 0-2, adequate organ function to receive cisplatin-based chemotherapy and signed informed consent. Patients were randomized between group A (pemetrexed 500 mg/m2 and cisplatin 75 mg/m2, both on day 1 every 3 weeks) and group B (gemcitabine 250 mg/m2 in 6-hours infusion, d1 and d 8, and cisplatin 75 mg/m2 on d 2, every 3 weeks). The primary endpoint was progression-free survival (PFS); secondary endpoints were ORR, toxicity, quality of life and OS. After progression, cross-over to the alternative regimen was recommended. Ninety-six patients entered the trial. Median age was 63 years, 75% were male and 68% had documented exposure to asbestos. Patients were randomized between Group A (CP, 51 pts) and Group B (C-GILI, 45 pts). With ORR over 45%, both regimens were effective. The main Grade 3-4 toxicity was neutropenia: 13.7% for arm A and 33.3% for arm B. Details on demographics, histologic features and effects of treatment are presented in the Table. Median PFS and OS for all patients are 9.4 and 18.6 months, respectively. Both arms of primary treatment were effective and well tolerated. Overall survival is among the longest reported so far. This trial confirms the value of C-GILI for treatment of mesothelioma. This treatment may find its indication as second-line treatment, as well as in the first line for deprivileged patients for whom the costs of pemetrexed may be prohibitive.Tabled 1Group A CP, 51 ptsGroup B C-GILI, 45 ptsDEMOGRAPHICSMale/Female35/1637/8Median age6364PS 0-1/PS 240/1136/9epitheliod/biphasic/sarcomatoid/unspec42/2/4/332/8/4/2PRIMARY TREATMENTORR, %48.950.0PFS (months, median)10.68.6% of pts with any grade ≥ 3 toxicity51.155.6SECOND-LINE TREATMENT AND SURVIVAL% of pts crossing-over to alternative combination77.861.1OS (months, median)20.618.6 Open table in a new tab