title: Pazopanib in advanced germ cell tumors after chemotherapy failure: results of the open-label, single-arm, phase 2 Pazotest trial.
abstract: 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.
  
  
  
  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%).
  
  
  
  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.
  
  
  
  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.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Necchi
authors.affiliation: Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Lo Vullo
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Giannatempo
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Raggi
authors.affiliation: Department of Radiology, Interventional Radiology, Nuclear Medicine and Radiotherapy, National Cancer Institute, 20133 Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Calareso
authors.affiliation: Pharmacy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Togliardi
authors.affiliation: Nuclear Medicine and PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Crippa
authors.affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pennati
authors.affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Zaffaroni
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale deiTumori, Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Perrone
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale deiTumori, Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Busico
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale deiTumori, Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Colecchia
authors.affiliation: Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Nicolai
authors.affiliation: Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Mariani
authors.affiliation: Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Salvioni
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D007191:Indazoles; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D011743:Pyrimidines / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D013736:Testicular Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
keywords: germ cell tumors; pazopanib; salvage therapy; testicular cancer