A Necchi1, S Lo Vullo2, P Giannatempo1, D Raggi1, G Calareso3, E Togliardi4, F Crippa5, M Pennati6, N Zaffaroni6, F Perrone7, A Busico7, M Colecchia7, N Nicolai8, L Mariani2, R Salvioni8. 1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 2. Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 3. Department of Radiology, Interventional Radiology, Nuclear Medicine and Radiotherapy, National Cancer Institute, 20133 Milan, Italy. 4. Pharmacy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 5. Nuclear Medicine and PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 6. Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 7. Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale deiTumori, Milano, Italy. 8. Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
Abstract
Background: Therapeutic options for patients with chemoresistant germ cell tumors (GCTs) are limited. Pazopanib is a selective tyrosine kinase inhibitor with distinct antiangiogenic activity. We aimed to evaluate pazopanib activity in patients with refractory GCT. Patients and methods: In the open-label, single-arm, phase 2 Pazotest study (NCT01743482), patient eligibility included failure of ≥2 platinum-based regimens, and allowed prior high-dose chemotherapy administration. Patients were given pazopanib 800 mg/day until disease progression (PD) or onset of unacceptable toxicity. Measurements of serum tumor markers (STM), computed tomography and FDG-PET were carried out at baseline, after 4 weeks of pazopanib treatment, and every 8 weeks thereafter. PD was defined as increasing levels of STM, increasing size of non-teratomatous masses, or appearance of new lesions. The study primary endpoint was progression-free survival (PFS, H0: 3-month PFS ≤ 10%, H1: ≥25%, α = 5%, β = 20%). Results: Forty-three patients were enrolled from May 2013 to July 2016. The number of prior chemotherapy regimens was: 2 (11.6%), 3 (51.2%), >3 (37.2%). Grade 3 adverse events were observed in six patients (13.9%). Overall, 70.3% of patients had reduced levels of STM after 4 weeks. There were 2 partial responses (4.7%), 19 cases of stable disease, and 16 cases of PD (6 not evaluable by RECIST). The median follow-up duration was 29.6 months. The 3-month PFS probability was 12.8% [95% confidence interval (CI): 5.7%-28.9%]. The 24-month OS probability was 14.2% (95% CI: 6.0%-33.7%). In patients with a >50% decline in STM, the 24-month OS probability was 24.1% (95% CI: 8.3%-69.6%). The small sample size was the major limitation. Conclusions: Despite pazopanib showed potent but short-lived activity in refractory GCT, long-term survival was obtained in a proportion of treated patients. According to the kinetics of pazopanib activity, this drug may be investigated in less pre-treated patients as an optimal bridging therapy preceding and/or combined with salvage chemotherapy.
Background: Therapeutic options for patients with chemoresistant germ cell tumors (GCTs) are limited. Pazopanib is a selective tyrosine kinase inhibitor with distinct antiangiogenic activity. We aimed to evaluate pazopanib activity in patients with refractory GCT. Patients and methods: In the open-label, single-arm, phase 2 Pazotest study (NCT01743482), patient eligibility included failure of ≥2 platinum-based regimens, and allowed prior high-dose chemotherapy administration. Patients were given pazopanib 800 mg/day until disease progression (PD) or onset of unacceptable toxicity. Measurements of serum tumor markers (STM), computed tomography and FDG-PET were carried out at baseline, after 4 weeks of pazopanib treatment, and every 8 weeks thereafter. PD was defined as increasing levels of STM, increasing size of non-teratomatous masses, or appearance of new lesions. The study primary endpoint was progression-free survival (PFS, H0: 3-month PFS ≤ 10%, H1: ≥25%, α = 5%, β = 20%). Results: Forty-three patients were enrolled from May 2013 to July 2016. The number of prior chemotherapy regimens was: 2 (11.6%), 3 (51.2%), >3 (37.2%). Grade 3 adverse events were observed in six patients (13.9%). Overall, 70.3% of patients had reduced levels of STM after 4 weeks. There were 2 partial responses (4.7%), 19 cases of stable disease, and 16 cases of PD (6 not evaluable by RECIST). The median follow-up duration was 29.6 months. The 3-month PFS probability was 12.8% [95% confidence interval (CI): 5.7%-28.9%]. The 24-month OS probability was 14.2% (95% CI: 6.0%-33.7%). In patients with a >50% decline in STM, the 24-month OS probability was 24.1% (95% CI: 8.3%-69.6%). The small sample size was the major limitation. Conclusions: Despite pazopanib showed potent but short-lived activity in refractory GCT, long-term survival was obtained in a proportion of treated patients. According to the kinetics of pazopanib activity, this drug may be investigated in less pre-treated patients as an optimal bridging therapy preceding and/or combined with salvage chemotherapy.
Authors: M Mego; D Svetlovska; M Chovanec; M Rečkova; K Rejlekova; J Obertova; P Palacka; Z Sycova-Mila; U De Giorgi; J Mardiak Journal: Invest New Drugs Date: 2019-06-01 Impact factor: 3.850
Authors: Ryan Ashkar; Darren R Feldman; Nabil Adra; Mohammad Abu Zaid; Samuel A Funt; Sandra K Althouse; Susan M Perkins; Christin I Snow; Kayla M Lazzara; Lina M Sego; David I Quinn; Nasser H Hanna; Lawrence H Einhorn; Costantine Albany Journal: Invest New Drugs Date: 2021-05-24 Impact factor: 3.651
Authors: Asaf Maoz; Koji Matsuo; Marcia A Ciccone; Shinya Matsuzaki; Maximilian Klar; Lynda D Roman; Anil K Sood; David M Gershenson Journal: Cancers (Basel) Date: 2020-05-29 Impact factor: 6.639