In the second article of a 2-part series, Mehmet A. Bilen, MD, explains how further findings from the phase 3 CARD trial support the wider role cabazitaxel should have in treating patients with metastatic castration-resistant prostate cancer.
Treatment and follow-up
Targeted OncologyTM: What were the secondary endpoints of the CARD trial (NCT02485691) and what were the results?
MEHMET A. BILEN, MD: [This trial evaluated patients with mCRPC] PSA response to cabazitaxel [Jevtana] vs abiraterone or enzalutamide, favoring [the 115 evaluable patients on cabazitaxel vs 111 on either abiraterone or enzalutamide] with a PSA response rate of 35.7% (n = 41) vs 13.5% (n = 15), respectively.1 Objective tumor response favored [the group of patients on] cabazitaxel vs the comparator arm who had measurable disease [at 36.5% (n = 23) vs 11.5% (n = 6), respectively]. Pain improvement and time to a symptomatic skeletal event, also favored patients on cabazitaxel, with a HR of 0.59 [95% CI, 0.35-1.01; P = .05].1
What were the safety findings of this study?
Safety is important, especially with these patients, but the rate of [patients who had] any grade 3 or greater adverse event [AE] was similar between the cabazitaxel [56.3%] arm compared with the abiraterone or enzalutamide arm [52.4%].2 Sometimes we have an impression that novel hormone agents are without AEs, but we can see more AEs [with them], especially fatigue and others with enzalutamide. Looking at the percentage of patients who experienced serious AEs, [they are closer in both arms] at about 39%. The number of patients with an AE leading to treatment discontinuation was higher on the chemotherapy vs either novel hormone agent [19.8% vs 8.9%, respectively].2
The patient-reported health-related quality of life outcomes were also important, as there is no big deterioration with chemotherapy.3 We saw some pain improvement with cabazitaxel [compared with the hormone agents at (P < .001)], but overall, the prostate-specific concerns well-being were similar between cabazitaxel vs androgen receptor-targeted therapy [P = .11].
How does dosing impact the use of cabazitaxel in these patients?
Now, we have…a trial comparing [a reduced dose of] cabazitaxel at 20 mg/m2 with [the approved dose of] 25 mg/m2 after docetaxel.4 [Events of grade 3 or higher] febrile neutropenia were higher in the 25 mg/m2 group [at 9.2%], but we see very little febrile neutropenia in patients on 20 mg/m2. I think clearly 20 mg/m2 is much better, as overall grade 3 or 4 toxicity is 39.7% [in the reduced dose group] vs 54.5% in the 25 mg/m2.
1. Fizazi K, Kramer G, Eymard J, et al. Pain response and health-related quality of life (HRQL) analysis in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel (CBZ) versus abiraterone or enzalutamide in the CARD study. J Clin Oncol. 2020;6(16);16-16. doi:10.1200/JCO.2020.38.6_suppl.16
2. de Wit R, de Bono J, Sternberg CN, et al; CARD Investigators. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. N Engl J Med. 2019;381(26):2506-2518. doi:10.1056/NEJMoa1911206
3. Fizazi K, Kramer G, Eymard JC, et al. Quality of life in patients with metastatic prostate cancer following treatment with cabazitaxel versus abiraterone or enzalutamide (CARD): an analysis of a randomised, multicentre, open-label, phase 4 study. Lancet Oncol. 2020;21(11):1513-1525. doi:10.1016/S1470-2045(20)30449-6
4. Eisenberger M, Hardy-Bessard AC, Kim CS, et al. Phase III study comparing a reduced dose of cabazitaxel (20 mg/m2) and the currently approved dose (25 mg/m2) in postdocetaxel patients with metastatic castration-resistant prostate cancer-PROSELICA. J Clin Oncol. 2017;35(28):3198-3206. doi:10.1200/JCO.2016.72.1076