ASCO 2020: Efficacy and Safety in Older Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Cabazitaxel versus Abiraterone or Enzalutamide in the CARD Study

(UroToday.com) Prostate cancer is the 2nd and 3rd leading cause of cancer death in the USA and in Europe, respectively,1,2 with most deaths occurring in men over the age of 75. In men with metastatic castrate-resistant prostate cancer (mCRPC), there are multiple treatment options available today, but the most appropriate treatment sequence and its impact on elderly patients are still unknown.

In this presented multicenter randomized, open-label CARD study (NCT02485691) led by Cora Sternberg, MD, FACP relevant mCRPC patients were enrolled between November 2015 and November 2018. Treatment with cabazitaxel was compared to treatment with abiraterone or enzalutamide in patients who had received prior docetaxel chemotherapy and had shown progression within 12 months while receiving the alternative androgen receptor-targeted agent. This can be shown in Figure 1, depicting the study design.

Figure 1:

Figure1_StudyDesign_ASCO2020.png


The initial published results in the New England Medical Journal demonstrated that radiographic progression-free survival and overall survival were significantly improved in patients treated with cabazitaxel versus those treated with abiraterone or enzalutamide.3 Specifically, radiographic progression-free survival (rPFS), which was the primary endpoint, showed a median of 8.0 versus 3.7 months with a hazard ratio of 0.54 (95% CI 0.40-0.73, p<0.001) in favor of cabazitaxel. Moreover, when examining median overall survival, the results showed 13.6 versus 11 months with a hazard ratio of 0.64 (95% 0.46-0.89, p=0.008), in favor of cabazitaxel. 

In this specific presented analysis of the CARD data at the ASCO 2020 virtual meeting, the authors evaluated the impact of age on the efficacy and safety of cabazitaxel versus abiraterone or enzalutamide. The authors conducted a subgroup analysis of the primary endpoint (radiographic progression-free survival) specifically in patients over the age of 70 and compared it to patients under the age of 70.

A total of 255 patients with metastatic castrate-resistant prostate cancer were randomly assigned to receive either cabazitaxel (n=129) or abiraterone or enzalutamide (n=126). The median duration of treatment for patients receiving cabazitaxel versus abiraterone or enzalutamide was 5.1 months versus 3 months for those above the age of 70, and 5.5 months versus 2.8 months for those under the age of 70.

The results showed that cabazitaxel significantly improved median radiographic progression-free survival in patients older than 70 years of age (8.2 vs. 4.5 months) and in patients under the age of 70 (7.4 vs. 3.2 months), as depicted in Figure 2. A similar advantage for cabazitaxel was also seen in median overall survival, both in patients over the age of 70 years (13.9 vs. 9.4 months) and in patients younger than 70 years of age (13.6 vs. 11.8 months), as shown in Figure 3. Additionally, progression-free survival (Figure 4), PSA response, tumor response, and pain response (Figure 5) were all improved with cabazitaxel compared to abiraterone or enzalutamide, regardless of age.

Figure 2:

Figure2_rPFS_age_ASCO2020.png

Figure 3:
OSAccordingtoAge_ASCO2020.png



Figure 4:

PFSaccordingtoage_ASCO2020.png

Figure 5:

PSA_Tumor_PainResponse_ASCO2020.png

When examining the safety profile, almost all patients had an adverse effect of any grade, irrespective of age. Generally, ≧ grade 3 adverse events occurred with higher frequency in patients older than 70 than in patients younger than 70. The more common grade three and above adverse effects in the cabazitaxel group in the older patients included fatigue/asthenia, diarrhea, and febrile neutropenia. In contrast, grade 3 and over adverse effects that occurred more frequently with the abiraterone or enzalutamide group in patients older than 70 included infection, renal disorders, and cardiac disorders. 

The authors concluded that cabazitaxel improved radiographic progression-free survival and median overall survival when compared to abiraterone or enzalutamide, regardless of patient age. All other secondary endpoints, including PSA, PSA response, objective tumor response, and pain response, all favored cabazitaxel as well, regardless of patient age. Cabazitaxel, abiraterone, and enzalutamide demonstrated a different safety profile with a higher rate of grade 3 or above adverse effects in patients over 70. Lastly, these results support the use of cabazitaxel over abiraterone or enzalutamide as a standard of care, irrespective of age in patients previously treated with docetaxel and the alternative androgen receptor-targeted agent.

Presented by: Cora N. Sternberg, MD, FACP Clinical Director of the Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, Former Chief of the Department of Medical Oncology at the San Camillo-Forlanini Hospital in Rome, Italy

Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, Twitter: @GoldbergHanan, at the 2020 ASCO Annual Meeting, Virtual Scientific Program #ASCO20, May 29-31, 2020.

References:
  1. Carioli G, Bertuccio P, Boffetta P, et al. European cancer mortality predictions for the year 2020 with a focus on prostate cancer. Annals of oncology : official journal of the European Society for Medical Oncology 2020; 31(5): 650-8.
  2. 1975-2017 SCSRC. Estimated New Cancer Cases and Deaths for 2020. https://seer.cancer.gov.statfacts/html/comon.html (accessed April 2020.)
  3. de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. The New England journal of medicine 2019; 381(26): 2506-18.

Related Content: 

View: Cabazitaxel Improves Pain and Health-Related Quality of Life Analysis in Patients with mCRPC, Results from the CARD Study - Karim Fizazi
View: The Clinical Implications and Heath-related Quality of Life Benefits: Reviewing the CARD Study Results in Men with mCRPC - Neal Shore
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