Two Clinical Factors May Predict PSA Response to Cabazitaxel

March 2, 2015

Two clinical factors may predict PSA response to cabazitaxel in men with metastatic castration-resistant prostate cancer.

In a small retrospective analysis, men with metastatic castration-resistant prostate cancer (CRPC) treated with cabazitaxel had greater prostate-specific antigen (PSA) responses if more time elapsed following their treatment with docetaxel and visceral disease was present.

A lower hemoglobin level (< 100 g/L) was associated with a worse overall survival (P = .024), although there was no specific value that could be used as a cutoff, according to the study authors.

No factors were statistically significantly linked to an improved overall survival.

A patient’s age of less than 65 years was associated with an increased risk of PSA progression (P = .023). Other factors associated with a PSA response were lung metastases (P = .040), although this did not translate to an improvement in overall survival.

Prior treatment with abiraterone did not impact response to cabazitaxel.

These results (Abstract 281) were presented by Daniel Yokom, MD, of Princess Margaret Hospital in Toronto, at the 2015 Genitourinary Cancers Symposium.

“Unfortunately, we were not able to identify any specific factors that were associated with improved overall survival,” said Yokom.

There are several second-line treatment options for metastatic CRPC, including cabazitaxel. The randomized open-label TROPIC trial previously compared cabazitaxel plus prednisone with mitoxantrone in men with metastatic CRPC who progressed following docetaxel therapy. Treatment with cabazitaxel improved overall survival by 2.4 months (12.7 months in the mitoxantrone arm vs 15.1 months in the cabazitaxel arm).

Yokom and colleagues analyzed the data to identify patient clinical factors that may predict a better response to cabazitaxel. “The TROPIC trial showed that many patients with metastatic CRPC can benefit from cabazitaxel. In the meantime, however, abiraterone, enzalutamide, and radium-223 have all been approved in the post-docetaxel setting. With so many agents to choose from, the purpose of this study was an attempt to inform physicians on patient and disease factors that predict which patients would do well or become worse on cabazitaxel,” Yokom told Cancer Network.

Yokom and colleagues evaluated baseline characteristics in 45 patients from 5 centers in Canada who were treated as part of an early access program. The median patient age was 65 years and the median PSA level was 249.7 ng/mL. Twenty-two percent of patients had visceral disease, and 69% had pain.

Both cabazitaxel and docetaxel belong to the taxane class of cytotoxic chemotherapies, binding to microtubules and interfering with cell division. The two agents have different side effect profiles, as well as different pharmacokinetic and pharmacodynamic properties, according to Yokom. “We do know that patients on the TROPIC trial who were heavily pretreated had the most benefit, so there is clearly a difference in the patients who will respond to cabazitaxel compared to docetaxel,” he said.

The analysis showed a similar response and side effect profile in the patients treated in regular practice and those treated as part of the TROPIC trial.

Further studies are needed to assess the clinical factors, and potentially, biomarkers that may predict which patients will have a better response to cabazitaxel after docetaxel treatment. “It will be important to continue to assess factors associated with response to cabazitaxel as we get more experience using the drug in routine practice, in particular, as an increasing number of patients are exposed to other agents such as enzalutamide or exposed to docetaxel early in the castrate-sensitive setting,” said Yokom.