Clinical trialPhase 3Prostate cancer

Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer

N Engl J Med · 2019255 patients

de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wülfing C, et al. N Engl J Med. 2019. 381:2506-2518

Study type: Clinical trial
Study name: CARD
Phase: Phase 3
Design: Randomised trial (1:1)
Sample size: 255 patients
Source: N Engl J Med · 2019
Trial registration: NCT02485691

In plain words

In men whose prostate cancer had grown after docetaxel chemotherapy and one of the tablets abiraterone or enzalutamide, cabazitaxel chemotherapy controlled the disease better and helped them live longer than switching to another hormone tablet (median 13.6 versus 11.0 months).

Key results

8.0 vs 3.7 months

Median imaging-based progression-free survival

Hazard ratio 0.54 (0.40–0.73); P<0.001

13.6 vs 11.0 months

Median overall survival

Hazard ratio for death 0.64 (0.46–0.89); P=0.008

35.7% vs 13.5%

PSA response

P<0.001

56.3% vs 52.4%

Grade 3 or higher adverse events

Drugs in this study:Abiraterone (Zytiga)Enzalutamide (Xtandi)

Dose and schedule cards

Cabazitaxel + prednisone (CARD)

mCRPC after docetaxel; in CARD, after progression within 12 months on abiraterone or enzalutamide, it was superior to switching to another ARPIEach drug’s schedule in the tableOn the page “Prostate cancer” · Castration-resistant disease (mCRPC): new-generation hormone therapy and chemotherapy

mCRPC after docetaxel; in CARD, after progression within 12 months on abiraterone or enzalutamide, it was superior to switching to another ARPI

Drug	Dose	Route	Schedule
Cabazitaxel	20 mg/m² (recommended label dose); 25 mg/m² in CARD and in selected patients	IV, 1-h infusion	Day 1, every 21 days
Prednisone	10 mg once daily	Oral	Continuously throughout treatment
ADT (GnRH agonist or antagonist, or prior orchiectomy)	Per formulation	—	Continuous

Cycle schedule: Cabazitaxel every 21 days; prednisone daily throughout treatment; ADT continuous
Duration: Until progression or unacceptable toxicity

Per the FDA label and the CARD trial, which used 25 mg/m² with primary G-CSF prophylaxis. Premedication 30 minutes before each dose (IV): an antihistamine (diphenhydramine 25 mg or equivalent), dexamethasone 8 mg and an H2 antagonist; antiemetic prophylaxis. Primary G-CSF prophylaxis is recommended in high-risk patients and should be considered for all patients at the 25 mg/m² dose. Contraindications: neutrophils ≤1500 and severe hepatic impairment (bilirubin more than 3 times the upper limit of normal); moderate hepatic impairment: 15 mg/m². Weekly blood counts during the first cycle and before each cycle. Dose reduction: from 25 to 20 and then 15 mg/m²; grade 3 or higher neuropathy: discontinue. Do not use PVC containers or infusion sets.

On the page “Prostate cancer” · Castration-resistant disease (mCRPC): new-generation hormone therapy and chemotherapy

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Cabazitaxel

Cabazitaxel 25 mg/m² IV over 1 hour on day 1 every 3 weeks, with prednisone 10 mg orally daily and primary G-CSF prophylaxis, until radiographic progression or unacceptable toxicity (median treatment duration 22 weeks).

2Alternative androgen-pathway inhibitor

A different hormonal agent (other than the previous one): abiraterone acetate 1000 mg orally once daily with prednisone 5 mg twice daily, or enzalutamide 160 mg orally once daily, until progression (median treatment duration 12.5 weeks).

Source of the regimen details: ClinicalTrials.gov NCT02485691

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

255 patients with mCRPC and effective castration (testosterone below 0.5 ng/mL) who had received at least 3 cycles of docetaxel (in the hormone-sensitive or castration-resistant setting, before or after a hormonal agent) and had progressed within 12 months of starting abiraterone or enzalutamide (before or after docetaxel); PSA at least 2 ng/mL.

Endpoints

Primary endpoint: imaging-based progression-free survival; secondary endpoints: survival, response and safety.

Safety and side effects

Grade 3 or higher adverse events occurred in 56.3% of the cabazitaxel group and 52.4% of the androgen-pathway inhibitor group; no new safety signals were seen.

Clinical significance and place in guidelines

CARD showed that after docetaxel and one ARPI, switching to another ARPI offers little benefit and cabazitaxel is the better option; this finding has been adopted in guidelines for treatment sequencing in mCRPC.

Limitations

Relatively small sample size and short follow-up; only patients who had progressed within 12 months on an ARPI were enrolled.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.