ESMO 2022: Cabazitaxel Every 2 Weeks Versus Every 3 Weeks in Older Patients with mCRPC: The CABASTY Randomized Phase III Trial

(UroToday.com) The 2022 ESMO annual meeting featured a prostate cancer session, including a presentation by Dr. Stephane Oudard discussing results of CABASTY, a randomized, phase III trial assessing cabazitaxel every 2 weeks versus every 3 weeks in older patients with mCRPC. Cabazitaxel 25 mg/m² every 3 weeks (q3w) + G-CSF prolongs overall survival (OS) vs abiraterone or enzalutamide in mCRPC patients previously treated with docetaxel and the alternative androgen-targeted agent.¹ Additionally, pilot studies suggest that cabazitaxel 16 mg/m² every 2 weeks (q2w) induces less severe neutropenia and could be useful for older patients unfit to receive cabazitaxel q3w.² The CABASTY trial aimed to confirm this hypothesis.

 Patients enrolled in CABASTY had progressive mCRPC (≥65 years of age, ECOG performance status 0-2, G8 >14 or ≤14 with reversible geriatric impairment) and were previously treated with docetaxel. Patients were randomized to cabazitaxel q3w + prednisone + G-CSF vs cabazitaxel q2w + prednisone + G-CSF and stratified by age (<70 vs ≥ 70 yrs) and G8 (>14 vs ≤14). The primary endpoint was the percentage of patients with grade ≥3 neutropenia and/or neutropenic complications (febrile neutropenia, neutropenic infection, sepsis). Secondary endpoints were radiographic progression-free survival (rPFS), objective tumor response, skeletal related events (SREs), PSA response, quality of life (not reported at ESMO 2022), safety, and OS:

Overall, 196 patients (median age, 74.0 years, with 79.6% ≥ 70 years; 19.9% G8 <14; 30.1% vulnerable or frail per SIOG guidelines; 86.7% treated with prior androgen-targeted agent) were randomized to cabazitaxel q3w (n = 97) versus cabazitaxel q2w (n = 99). Baseline characteristics for the two groups is as follows:

The rate of Grade ≥3 neutropenia and/or neutropenic complications was significantly higher with cabazitaxel q3w vs cabazitaxel q2w (62.9% vs 5.1%; OR 0.03, 95% CI 29.5-48.9, p<0.001):

There was no difference in the secondary endpoints of radiological PFS or OS between the two groups: 

Additionally, there was no difference in PSA response >=50% and objective tumor response: 

Relative dose intensity for cabazitaxel q3w vs cabazitaxel q2w was comparable (92.3% vs 91.6%). Grade ≥3 adverse events were more common with cabazitaxel q3w (72.9% vs 58.2%). One patient (cabazitaxel q3w arm) died of neutropenic complications. There were no new safety signals observed.

Dr. Oudard concluded his presentation discussing the results of CABASTY, a randomized, phase III trial assessing cabazitaxel every 2 weeks versus every 3 weeks in older patients with mCRPC with the following take-home messages:

• The CABASTY trial met its primary endpoint – in this heavily pretreated elderly mCRPC population (50% >= 75 years), cabazitaxel 16 mg/m² q2w plus G-CSF significantly reduced the rate of grade >= 3 neutropenia and/or neutropenic complications versus cabazitaxel 25 mg/m² q3w plus G-CSF
• Secondary efficacy endpoints (OS, rPFS, PSA response, objective tumor response) were comparable between the two arms
• There were no new safety signals with cabazitaxel 16 mg/m² q2w plus G-CSF
• Cabazitaxel 16 mg/m² q2w plus G-CSF should be offered to older patients with mCRPC who are considered unfit for the standard cabazitaxel regimen

Presented by: Stephane Oudard, Oncology Department, HEGP - Hopital Europeen Georges-Pompidou - APHP - University de Paris, Paris, France

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 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022. 

References:

1. de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med 2019 Dec 26;381(26):2506-2518.
2. Clement-Zhao A, Auvray M, Aboudagga H, et al. Safety and efficacy of 2-weekly cabazitaxel in metastatic castration-resistant prostate cancer. BJU Int. 2018 Feb;121(2):203-208.