Ronald de Wit, MD, PhD, group leader, Experimental Systematic Therapy of Urogenital Cancers program, Erasmus MC Cancer Institute, Rotterdam, Netherlands, discusses the adverse events (AEs) with cabazitaxel (Jevtana) in the phase III CARD trial in patients with metastatic castration-resistant prostate cancer (mCRPC).

In the phase III CARD trial, cabazitaxel showed a significant improvement in overall survival and radiographic progression-free survival versus enzalutamide (Xtandi) or abiraterone acetate (Zytiga) in the third-line treatment of patients with mCRPC.

Additionally, the rate of AEs was comparable between arms despite the fact that the median duration of treatment was longer in patients receiving cabazitaxel versus those receiving an androgen receptor (AR) inhibitor. The rate of serious AEs in the cabazitaxel and AR inhibitor arms was 38.9% and 38.7%, respectively. Neutropenic fever was a concern with cabazitaxel, says de Wit; however, the use of primary prophylactic granulocyte-colony stimulating factor was required in each cycle of cabazitaxel therapy.

Regarding grade ≥3 AEs, patients in the cabazitaxel arm were more likely to experience severe asthenia/fatigue (4.0 vs 2.4%), diarrhea (3.2 vs 0%), peripheral neuropathy (3.2 vs 0%), and febrile neutropenia (3.2 vs 0%) compared with those in the AR inhibitor arm. However, patients in the cabazitaxel arm were less likely to experience grade ≥3 renal disorders (3.2 vs 8.1%), musculoskeletal pain (1.6 vs 5.6%), cardiac disorders (0.8 vs 4.8%) and spinal cord or nerve root disorders (2.4 vs 4.0%) compared with those in the AR inhibitor arm.

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Dr. de Wit on the AEs With Cabazitaxel in the CARD Trial in mCRPC

Ronald de Wit, MD, PhD, group leader, Experimental Systematic Therapy of Urogenital Cancers program, Erasmus MC Cancer Institute, Rotterdam, Netherlands, discusses the rationale for the randomized phase III CARD trial which showed a significant overall survival (OS) benefit with third-line cabazitaxel (Jevtana) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Docetaxel and the androgen signaling inhibitors, abiraterone acetate (Zytiga) and enzalutamide (Xtandi) are frequently used in the metastatic castration-resistant setting. However, once patients progress on one of the androgen signaling inhibitors, they are not likely to respond to the other agent, de Wit explains. Cabazitaxel, though available, is often used as the last intervention.

As such, patients in the CARD trial were randomized to receive either cabazitaxel or abiraterone or enzalutamide, depending on which androgen signaling inhibitor they had received previously. 

After a median follow-up of 9.2 months, investigators reported a median OS of 13.6 months with cabazitaxel versus 11.0 months with either abiraterone or enzalutamide (HR 0.64; 95% CI 0.46—0.89; 

Ronald de Wit, MD, PhD, discusses the rationale for the randomized phase III CARD trial which showed a significant overall survival benefit with third-line cabazitaxel in patients with metastatic castration-resistant prostate cancer.
 

Dr. de Wit on Rationale for Phase III CARD Trial in Metastatic CRPC

Ronald de Wit, MD, PhD, group leader, Experimental Systematic Therapy of Urogenital Cancers program, Erasmus MC Cancer Institute, Rotterdam, Netherlands, discusses findings with pembrolizumab (Keytruda) in non-muscle invasive bladder cancer (NMIBC).

Pembrolizumab demonstrated encouraging antitumor activity in patients with high-risk NMIBC whose tumors were unresponsive to Bacillus Calmette-Guérin, according to interim findings from an ongoing single-arm open-label phase II study. At 3 months, 38.8% (n=40) of patients had a complete response (CR). The median time to CR was 12.4 weeks (95% CI, 10.4-19.3). Of the 40 patients who had a CR, 29 (72.5%) had ongoing responses and about 80% of patients had a CR duration ≥6 months. The median duration of CR had not been reached, and de Wit says that many patients are still in response. Additionally, no patients progressed to muscle-invasive disease.

These results are encouraging, de Wit says, and this may provide another option for these patients, whose only option currently is radical cystectomy. Pembrolizumab is an important new avenue of treatment, as it can preserve the bladder and avoid subjecting patients to the morbidity and mortality of a radical cystectomy, or the possibility of progression to invasive disease.  

Ronald de Wit, MD, PhD, group leader, Experimental Systematic Therapy of Urogenital Cancers program, Erasmus MC Cancer Institute, Rotterdam, Netherlands, discusses findings with pembrolizumab (Keytruda) in non-muscle invasive bladder cancer.

Ronald de Wit, MD, PhD

Articles

Dr. de Wit on the AEs With Cabazitaxel in the CARD Trial in mCRPC

Dr. de Wit on Rationale for Phase III CARD Trial in Metastatic CRPC

Dr. de Wit Discusses Findings With Pembrolizumab in NMIBC