Objectives: Second-line chemotherapy is not a standard of care in patients with malignant pleural mesothelioma (MPM) that progresses after first-line treatment with cisplatin and pemetrexed. In pre-clinical models, the combination of gemcitabine (GEM) and imatinib mesylate (IM), compared with GEM alone, led to a further tumor growth inhibition and improved survival. This phase II study evaluates the antitumor activity of a combination of IM and GEM in platinum-pemetrexed-pretreated MPM patients expressing PDGFR-beta and/or cKIT by immunohistochemistry (IHC).Patients and methods: GEM (1000 mg/m(2)) was given on days 3 and 10; IM (400 mg) was taken orally on days 1-5 and 8-12 of a 21-day cycle. The primary endpoint was the 3-month progression-free survival (PFS) rate. The study follows the optimal two-stage design of Simon. A 3-month PFS target of 75 % was required. With a probability error alpha = 10 % and a power of 80 %, the calculated sample size was 22 patients. In particular, in the first step, six out of nine patients and globally 14/22 patients free from progressive disease at 3 months were required. Secondary endpoints included response rate, duration of response, toxicity and overall survival (OS).Results: In total, 23 patients were enrolled (ECOG PS 0-1/2: 9/13; one previous line/>= two previous lines: 10/ 13). Partial response was achieved in four patients (17.4 %) and stable disease in 11 (47.8 %) with a disease control rate of 65.3 %. After a median follow-up of 34.5 months, median PFS and OS were 2.8 and 5.7 months, respectively. The 3-month PFS rate was 39.1 % (9/23 patients). All-grade drug-related adverse events occurred in 17 (73.9 %) patients. Grade 3 treatment-related adverse events were observed in four (17 %) patients.Conclusions: The combination of IM and GEM is well tolerated in platinum-pemetrexed-pretreated MPM patients expressing PDGFR-beta and/or cKIT by IHC, but it does not show a significant PFS benefit.
A phase II study of the combination of gemcitabine and imatinib mesylate in pemetrexed-pretreated patients with malignant pleural mesothelioma / Zucali, Paolo Andrea; Perrino, Matteo; De Vincenzo, Fabio; Giordano, Laura; Cordua, Nadia; D'Antonio, Federica; Santoro, Armando. - In: LUNG CANCER. - ISSN 0169-5002. - 142:(2020), pp. 132-137. [10.1016/j.lungcan.2020.02.005]
A phase II study of the combination of gemcitabine and imatinib mesylate in pemetrexed-pretreated patients with malignant pleural mesothelioma
Giordano, LauraMembro del Collaboration Group
;D'Antonio, Federica
Membro del Collaboration Group
;
2020
Abstract
Objectives: Second-line chemotherapy is not a standard of care in patients with malignant pleural mesothelioma (MPM) that progresses after first-line treatment with cisplatin and pemetrexed. In pre-clinical models, the combination of gemcitabine (GEM) and imatinib mesylate (IM), compared with GEM alone, led to a further tumor growth inhibition and improved survival. This phase II study evaluates the antitumor activity of a combination of IM and GEM in platinum-pemetrexed-pretreated MPM patients expressing PDGFR-beta and/or cKIT by immunohistochemistry (IHC).Patients and methods: GEM (1000 mg/m(2)) was given on days 3 and 10; IM (400 mg) was taken orally on days 1-5 and 8-12 of a 21-day cycle. The primary endpoint was the 3-month progression-free survival (PFS) rate. The study follows the optimal two-stage design of Simon. A 3-month PFS target of 75 % was required. With a probability error alpha = 10 % and a power of 80 %, the calculated sample size was 22 patients. In particular, in the first step, six out of nine patients and globally 14/22 patients free from progressive disease at 3 months were required. Secondary endpoints included response rate, duration of response, toxicity and overall survival (OS).Results: In total, 23 patients were enrolled (ECOG PS 0-1/2: 9/13; one previous line/>= two previous lines: 10/ 13). Partial response was achieved in four patients (17.4 %) and stable disease in 11 (47.8 %) with a disease control rate of 65.3 %. After a median follow-up of 34.5 months, median PFS and OS were 2.8 and 5.7 months, respectively. The 3-month PFS rate was 39.1 % (9/23 patients). All-grade drug-related adverse events occurred in 17 (73.9 %) patients. Grade 3 treatment-related adverse events were observed in four (17 %) patients.Conclusions: The combination of IM and GEM is well tolerated in platinum-pemetrexed-pretreated MPM patients expressing PDGFR-beta and/or cKIT by IHC, but it does not show a significant PFS benefit.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
