Paolo Andrea Zucali1, Matteo Perrino2, Fabio De Vincenzo3, Laura Giordano4, Nadia Cordua5, Federica D'Antonio6, Armando Santoro7. 1. Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Electronic address: paolo.zucali@humanitas.it. 2. Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Electronic address: matteo.perrino@cancercenter.humanitas.it. 3. Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Electronic address: fabio.de_vincenzo@cancercenter.humanitas.it. 4. Biostatistic Unit, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Electronic address: laura.giordano@cancercenter.humanitas.it. 5. Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Electronic address: nadia.cordua@cancercenter.humanitas.it. 6. Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Electronic address: federica.dantonio@cancercenter.humanitas.it. 7. Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Electronic address: armando.santoro@cancercenter.humanitas.it.
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-β and/or cKIT by immunohistochemistry (IHC). PATIENTS AND METHODS: GEM (1000 mg/m2) 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 α = 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-β and/or cKIT by IHC, but it does not show a significant PFS benefit.
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 MPMpatients expressing PDGFR-β and/or cKIT by immunohistochemistry (IHC). PATIENTS AND METHODS: GEM (1000 mg/m2) 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 α = 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 MPMpatients expressing PDGFR-β and/or cKIT by IHC, but it does not show a significant PFS benefit.
Authors: Hely Ollila; Juuso Paajanen; Henrik Wolff; Ilkka Ilonen; Eva Sutinen; Katja Välimäki; Arne Östman; Sisko Anttila; Eeva Kettunen; Jari Räsänen; Olli Kallioniemi; Marjukka Myllärniemi; Mikko I Mäyränpää; Teijo Pellinen Journal: J Pathol Clin Res Date: 2021-05-06