Third-line Cabazitaxel Benefit Demonstrated For metastatic CRPC Patients

Cabazitaxel Benefit Demonstrated For metastatic CRPC Patients
Patients with metastatic castration-resistant prostate cancer have better outcomes with third-line cabazitaxel than with receipt of a second androgen signalling-targeted agent
Date: 08 Oct 2019
Author: By Lynda Williams, Senior medwireNews Reporter
Topic: Prostate Cancer / Anticancer Agents
medwireNews: For men with metastatic castration-resistant prostate cancer (CRPC) who have progressed after docetaxel and use of enzalutamide or abiraterone, cabazitaxel offers significantly better survival than treatment with the alternative androgen signalling-targeted agent, research suggests.

The CARD trial findings were presented at the ESMO Congress 2019 in Barcelona, Spain and simultaneously reported in The New England Journal of Medicine.

After a median of 9.2 months, imaging-based progression or death had occurred in 73.6% of the metastatic CRCP 129 patients who were randomly assigned to receive cabazitaxel 25 mg/m2 every 3 weeks, alongside prednisone 10 mg/day and granulocyte colony-stimulating factor therapy at each cycle.

This rate was significantly lower than the 80.2% reported for the 126 patients who instead were randomly assigned to receive enzalutamide or abiraterone, according to which agent they had previously received, giving a significant hazard ratio (HR) for progression or death of 0.54 in favour of the taxane.

Post hoc analyses confirmed that this superior outcome with cabazitaxel was true regardless of whether the second androgen signalling-targeted inhibitor was enzalutamide or abiraterone, reported presenting author Ronald de Wit, from Erasmus Medical Center in Rotterdam, the Netherlands, and co-workers.

Patients using cabazitaxel also achieved a significantly longer duration of overall survival than those given a second androgen signalling-targeted agent (median 13.6 vs 11.0 months, HR=0.64) as well as better progression-free survival when including prostate-specific antigen (PSA) and pain progression (median 4.4 vs 2.7 months, HR=0.52).

These benefits with cabazitaxel were accompanied by higher rates of PSA response (35.7 vs 13.5%) and tumour response (36.5 vs 11.5%), the researchers say.

Of note, there was a comparable incidence of serious adverse events (AEs) in the cabazitaxel and second androgen signalling-inhibitor trial arms (38.9 vs 38.7%), although cabazitaxel was associated with a higher rate of discontinuation because of AEs (19.8 vs 8.9%).

Cabazitaxel-treated patients were more likely than those given enzalutamide or abiraterone to experience grade 3 and more severe asthenia/fatigue (4.0 vs 2.4%), diarrhoea (3.2 vs 0%), peripheral neuropathy (3.2 vs 0%), and febrile neutropenia (3.2 vs 0%), but were less likely to develop 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%).

“The results of the CARD trial are in agreement with those of previous studies that have shown poor outcomes with a second androgen-signaling–targeted inhibitor”, de Wit and co-workers note.

“This is probably due to the fact that these agents target the same pathway and thus share common mechanisms of resistance” whereas “taxanes, owing to their different mechanism of action, are able to overcome several mechanisms of resistance to androgen-signaling-targeted inhibitors”, they hypothesise.



References

de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer . N Engl J Med; Advance online publication 30 September 2019. DOI: 10.1056/NEJMoa1911206

de Wit R, Kramer G, Eymard J-C, et al. CARD: Randomized, open-label study of cabazitaxel (CBZ) vs abiraterone (ABI) or enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC). ESMO Congress 2019 ; Barcelona, Spain: 27 September–1 October. LBA13