Cabazitaxel increases progression-free survival in mCRPC patients irrespective of age

July 2021 Cancer trials Tobias Rawson

Patients with metastatic castration-resistant prostate cancer (mCRPC) have limited treatment options, following progression on abiraterone/enzalutamide. Following the results of the CARD study, the European Society of Medical Oncology (ESMO) recommend the use of cabazitaxel in mCRPC patients who have already received docetaxel. In a more recent analysis of the same trial, the efficacy and safety of cabazitaxel was examined in younger (<70 yrs) and older (>70 yrs) patients.

CARD study design

This phase 4 study enrolled 255 mCRPC patients, who had previously received docetaxel and an androgen-signalling-targeted inhibitor (abiraterone/enzalutamide) were randomised 1:1 to receive either cabazitaxel (25 mg/m2 intravenously every 3 weeks), plus prednisone and granulocyte colony-stimulating factor, or the opposite androgen-signalling-targeted inhibitor to what each patient had previously received (1000mg abiraterone plus prednisone daily or 160mg enzalutamide daily). Analysis of radiographic progression-free survival (rPFS) (primary endpoint) and safety was stratified by age (>70 yrs / <70 yrs).

Reduction in the risk of progression by 53%

Following randomisation, 135 patients were >_70 yrs, with an overall median age of 76 years of age. Cabazitaxel was able to reduce the risk of radiographic progression in younger patients by 53%, compared to abiraterone/enzalutamide (median rPFS <70 yrs: 7.4 vs. 3.2 mo; HR[95%CI]: 0.47[0.30-0.74], P< 0.001). Older patients also received a statistically significant benefit with cabazitaxel (median rPFS >_70 yrs: 8.2 vs. 4.5 mo; HR[95%CI]: 0.58[0.38-0.89], P= 0.012). Treatment with cabazitaxel also resulted in a numerical advantage in overall survival (OS) in both younger and older patients. (median OS < 70 yrs: 13.6 vs. 11.8 mo; HR[95%CI]: 0.66[0.41-1.08], P= 0.093) ; (median OS >_70 yrs: 13.9 vs. 9.4 mo; HR[95%CI]: 0.66[0.41-1.06], P= 0.084). Additionally, prostate-specific antigen, as well as tumour and pain responses were in favour of cabazitaxel, irrespective of age. Grade >_3 treatment-emergent adverse events (TEAEs) were higher in patients treated with cabazitaxel across all ages. Grade >_3 TEAEs occurred in 48% vs. 42% of younger patients, respectively. Similarly, older patients experienced grade >_3 TEAEs at rates of 58% and 49%. However, in older patients, cardiac adverse events were more frequent in those treated with abiraterone/enzalutamide. Conversely, asthenia and diarrhoea were more frequent with cabazitaxel.

Conclusion

In patients with advanced, treatment-refractory prostate cancer, cabazitaxel was able to provide a superior radiographic progression-free survival, irrespective of age, compared to abiraterone or enzalutamide. Furthermore, although TEAEs were more frequent in older patients, the safety profile of cabazitaxel was manageable across both age groups.

Reference

Sternberg CN, et al., Efficacy and safety of cabazitaxel versus abiraterone or enzalutamide in older patients with metastatic castration-resistant prostate cancer in the CARD study. Euro Urol. 2021; 80(2).   

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