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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbermdx124
Pages (from-to)1346-1351
Number of pages6
JournalAnnals of Oncology
Volume28
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

Keywords

  • Germ cell tumors
  • Pazopanib
  • Salvage therapy
  • Testicular cancer

ASJC Scopus subject areas

  • Hematology
  • Oncology

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