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

Authors

Andrea Necchi

Andrea Necchi

Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

Andrea Necchi , Daniele Raggi , Patrizia Giannatempo , Giuseppina Calareso , Elena Togliardi , Nicola Nicolai , Flavio Crippa , Luigi Mariani , Roberto Salvioni

Organizations

Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, National Cancer Institute of Milan, Milan, Italy, Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Research Funding

Other

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

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Abstract Details

Meeting

2016 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Prostate Cancer; Urothelial Carcinoma; Penile, Urethral, and Testicular Cancers

Track

Urothelial Carcinoma,Prostate Cancer,Penile, Urethral, and Testicular Cancers

Sub Track

Penile, Urethral, and Testicular Cancers

Clinical Trial Registration Number

NCT01743482

Citation

J Clin Oncol 34, 2016 (suppl 2S; abstr 481)

DOI

10.1200/jco.2016.34.2_suppl.481

Abstract #

481

Poster Bd #

L6

Abstract Disclosures

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