Safety Results with Cabazitaxel Support Wider Use in mCRPC

Case Summary

• A 75-year-old man presented with intermittent left hip pain​.
• Physical exam: unremarkable except for a prostate nodule on rectal exam​
• ECOG performance status: 1​

Clinical workup ​

• Prostate-specific antigen (PSA) level: 16.2 ng/mL​
• Gleason score 5 + 4, grade group 5​ per transrectal ultrasound–guided biopsy
• Bone scan and abdominal/pelvic CT scan​ were negative.
• X-ray of the pelvis indicated osteoarthritis.
• The patient was diagnosed with category cT2N0M0​ prostate cancer.
• Germline and somatic genetic testing were negative for pathogenic alterations​.

Treatment and follow-up​

• External beam radiation therapy plus androgen deprivation therapy (ADT) was initiated (planned for 24 months). Six months after initiation of therapy, PSA was undetectable, and the patient was asymptomatic​.
• Unfortunately, the patient did not return for regularly scheduled PSA follow-ups, and​ 36 months later, he experienced progression.
• The patient received ADT plus enzalutamide (Xtandi) 160 mg once daily before noon; his initial PSA (nadir, 3.9 ng/mL) and symptom response​ were good.
• Because of a busy travel schedule, the patient did not return for routine PSA monitoring​.
• He developed metastatic castration-resistant prostate cancer (mCRPC) and was started on docetaxel 75 mg/m² intravenously once every 3 weeks plus prednisone 10 mg once a day.
• The patient responded clinically to treatment (ie, resolution of pain, improved energy, and declining PSA)​.
• He completed 4 cycles of treatment but developed worsening bilateral digital neuropathy throughout therapy. Therapy was stopped, and cycle 5 was not administered.​
• Three months later, the patient showed rising PSA, new back pain, and shortness of breath on exertion​.
• Abdominal/pelvic CT showed enlargement of known pelvic lymph nodes and 1 new liver lesion (< 2 cm).

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.

^References

^{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}