(UroToday.com) The European Society of Medical Oncology (ESMO) 2021 annual meeting’s non-prostate cancer mini-oral session included a presentation by Dr. Giulia Baciarello discussing results from the phase 2 CABA-GCT trial. Men with advanced germ cell tumors with cancer progression after 2-3 lines of chemotherapy have a poor prognosis with currently no standard treatment. Taxanes have established activity in germ cell tumor. Cabazitaxel may cross the blood-brain barrier (the brain is a frequent site of progression in highly pretreated patients) and has limited peripheral neuro-toxicity, two major potential advantages for these patients. At the 2021 ESMO congress, Dr. Baciarello and colleagues presented results of this phase 2 trial of cabazitaxel in male patients with chemotherapy pre-treated metastatic germ-cell tumors.
In this multicenter phase II study, men with cancer progression after at least 2 chemotherapy regimens for advanced germ cell tumor received cabazitaxel 25 mg/m2 every 3 weeks, for a maximum of 6 cycles. The trial design for the CABA-GCT trial is as follows:
The primary endpoint was the favorable response rate, defined as complete response or partial response with normalized tumor markers. Using a 1-step Fleming design, 34 patients 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 cabazitaxel is active in this setting (exact type I error = 9%, exact type II error = 7%). Tumor response was assessed at week 6 and at the end of treatment.
From September 2014 to October 2019, 34 patients from 5 centers were included, including 14.7% with mediastinal primary GCT, and 94.2% with nonseminomatous GCT. These patients had 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, 2/34 (5.9%, 95% CI 1.0-21.1) achieved a favorable response. Exploratory analyses included overall disease control rate (complete response, partial response with normalized tumor markers, partial response with elevated tumor markers or stable disease), observed in 9 (26.5%, 95% CI 13.5-44.6) patients at end of treatment. The 6-month PFS rate was 20.6% (95% CI 10.4 - 36.8) and the 6-month OS 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 week 6, 10 patients (29.4%) and 6 patients (17.6%) had a ≥30% reduction in hCG and AFP, respectively. Grade 3 adverse events were reported in 7 patients (20.6%), including febrile neutropenia in 4/34 patients (11.8%); 1/4 did not receive G-CSF prophylaxis. Only 1/34 patient (2.9%) developed a grade 2 peripheral neuropathy after the 1st cycle.
Dr. Baciarello concluded her presentation of the CABA-GCT trial with the following take-home messages:
- Cabazitaxel can be safely administered in men with refractory nonseminomatous germ cell tumor
- The small cohort of men with brain metastases limited the efficacy analysis in this subgroup
- Similar to other drugs, cabazitaxel has modest activity as a single-agent in highly pretreated men who received previous taxane-based or high-dose chemotherapy plus germ cell support in 70% of cases
Presented by: Giulia Baciarello, MD, Medical Oncology 1, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, Milan, Italy
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.