655MO - A prospective phase II trial of cabazitaxel in male patients with chemotherapy pre-treated metastatic germ-cell tumors: The CABA-GCT study

Background

Men with advanced germ cell tumor (GCT) with cancer progression after 2-3 lines of chemotherapy have a poor prognosis with currently no standard treatment. Taxanes have established activity in GCT. Cabazitaxel (CABA) may cross the blood-brain barrier and has limited peripheral neuro-toxicity, two major potential advantages for these patients (pts).

Methods

In this multicentre phase II study, men with cancer progression after at least 2 chemotherapy regimen for advanced GCT received CABA 25 mg/m² every 3 weeks, for a maximum of 6 cycles. The primary endpoint was the favorable response (FR) rate, defined as complete response (CR) or partial response (PR) with normalized tumor markers (m-). For each patient we retained his best response. Using a 1-step Fleming design, 34 pts were required to show an improvement from 5% to 20%, with a type I error of 5% and a type II error of 10%. If 4 favorable responses or more were observed, it would be concluded that CABA is active in this setting (exact type I error = 9%, exact type II error = 7%). Tumor response was assessed at W6 and at the end of treatment (EOT).

Results

From September 2014 to October 2019, 34 pts from 5 centres were included and received 2 (47.1%), 3 (35.3%), or ≥4 (17.6%) previous lines of chemotherapy, respectively (including n=11 (32.5%) with previous high-dose chemotherapy). Overall, 3/34 (8.8%, 95% CI: 2.3-24.8] achieved a FR. (1 at W6, 2 at EOT). Exploratory analyses included overall disease control rate (CR, PRm-, PRm+ or SD), observed in 9 (26.5%; 95%CI: 13.5-44.6) pts at EOT. The 6-month PFS rate was 20.6% (95% CI: 10.4 - 36.8) and the 6-month OS was was 58.8% (95% CI: 42.2-73.6). No evidence of local anticancer activity was shown in the 4 patients with brain metastases (1 progression, 3 NE). At W6, 10 pts (29.4%) and 6 pts (17.6%) had a ≥30% reduction in hCG and AFP, respectively. G3 adverse events were reported in 7 pts (20.6%). Febrile neutropenia occurred in 4/34 pts (11.8%); 1/4 did not receive G-CSF prophylaxis. Only 1/34 pt (2.9%) developed a G2 peripheral neuropathy after the 1^st cycle.

Conclusions

CABA can be safely administered in men with refractory NSGCT and it has modest and similar activity to other drugs used in monotherapy in this setting.

Clinical trial identification

EudraCT 2013-000286-36.

Editorial acknowledgement

Legal entity responsible for the study

Institut Gustave Roussy.

Funding

Sanofi.

Disclosure

G. Baciarello: Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Invited Speaker: Gensenta. G. Gravis: Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Speaker’s Bureau: BMS; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Alliance Merck-Pfizer; Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Sanofi. A. Fléchon: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: AAA. E. Colomba: Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Tesaro; Financial Interests, Personal, Invited Speaker: GSK. R. Flippot: Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Pfizer. K. Fizazi: Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Advisory Board: Curevac; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Invited Speaker: Janssen; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Orion; Financial Interests, Institutional, Research Grant: Pfizer. All other authors have declared no conflicts of interest.