Pazopanib in advanced germ cell tumors after chemotherapy failure: results of the open-label, single-arm, phase 2 Pazotest trial.

Therapeutic options for patients with chemoresistant germ cell tumors (GCT) 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 (HDCT) 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 performed at baseline, after 4 weeks of pazopanib treatment, and every 8 weeks thereafter. PD was defined as increasing levels of STM, increasing size of nonteratomatous 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 6 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 three-month PFS probability was 12.8% (95%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.

Annals of oncology : official journal of the European Society for Medical Oncology. 2017 Apr 05 [Epub ahead of print]

A Necchi, S Lo Vullo, P Giannatempo, D Raggi, G Calareso, E Togliardi, F Crippa, M Pennati, N Zaffaroni, F Perrone, A Busico, M Colecchia, N Nicolai, L Mariani, R Salvioni

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Pharmacy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Nuclear Medicine and PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Department of Experimental Oncology and Molecular Medicine (DOSMM), Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.