Pazopanib in patients (pts) with advanced germ cell tumors (GCT): Results from an open-label, single-group, phase 2 trial (Pazotest-01).

Abstract

481 Background: Therapeutic options for pts with chemoresistant GCT are limited and prognosis is poor. Pazopanib (PZP) is a potent and selective tyrosine kinase inhibitor (TKI) with distinct antiangiogenic activity. Methods: Pazotest-01 enrolled pts who were given PZP 800 mg/day orally until disease progression (PD) or unacceptable toxicity. Eligibility included failure of ≥ 2 platinum-based regimens, including high-dose chemotherapy (HDCT). Baseline serum tumor markers (STM), a computed tomography and a FDG-PET were repeated after 4 wks of PZP and q8 weeks thereafter. The primary endpoint was PFS (H0: 3-month PFS ≤ 10%, H1: ≥ 25%, α = 5%/β = 20%). PD was defined as rising STM, an increase in tumour size, or the appearance of new lesions. An enrolment of 43 pts was planned from a single center (NCT01743482). Results: From 05/2013 to 07/2015, 32 pts were enrolled (27 [84.4%] with nonseminoma, including 5 [15.6%] with malignant transformation, and 5 seminomas). 5 (15.6%) had primary mediastinal nonseminoma (PMNSGCT). 3 had failed two prior regimens, 15 (46.9%) three, and 14 (43.7%) > 3 regimens, including HDCT in 15 (46.9%). 20 (62.5%) had liver, bone, or brain metastases. 29 pts had elevated STM: 18 of them (62.1%) had a STM decline (mean: -53.5%). 1 PR, 19 SD (64.5% clinical benefit) and 12 PD were obtained according to RECIST v1.1. 8 pts (25%) had a densitometric and 10 (29%) a metabolic partial response. The kinetics of response was predictable in all pts: best response was seen within 4wks of starting PZP, neither PR nor STM decline occurred > 4wks. Median follow up was 15.7 months. Median PFS was 2.73 months, 3-month PFS was 28% (95%CI: 13.3-44.8). 4 pts (12.5%) were progression-free at > 5 months FUP (including 1 PMNSGCT). Median OS was 4.9 months. 4 cases (12.5%) of G3 AST/ALT increase, and 1 case of G3 diarrhea and vomiting each have been observed. 7 pts (21.9%) had G2 asthenia. Conclusions: PZP is endowed with potent anti-tumor activity in extensively pretreated patients with GCT. PZP was well tolerated, and the combination with paclitaxel is a rational next step to improve the response duration. The primary endpoint is pending confirmation in the full sample-size, and mature results will be presented. Clinical trial information: NCT01743482.