Cabazitaxel No Better Than Docetaxel in Metastatic CRPC

June 8, 2016

Cabazitaxel at two different doses was no better than docetaxel with regard to OS or PFS in men with metastatic castration-resistant prostate cancer.

Cabazitaxel at two different doses was no better than docetaxel with regard to overall survival (OS) or progression-free survival (PFS) in men with metastatic castration-resistant prostate cancer (mCRPC), according to results of the phase III FIRSTANA trial. The results were presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract 5006).

Cabazitaxel is a semisynthetic taxane. “It was initially selected from a wide variety of taxanes to be able to overcome taxane resistance,” said A. Oliver Sartor, MD, of Tulane University in New Orleans, who presented the study. In preclinical studies the drug was particularly active against docetaxel-resistant cells, and it was approved as a second-line option in 2010 based on results of the phase III TROPIC trial.

“Many individuals have been comparing a variety of agents against placebo, mitoxantrone, and other therapies that are not known to prolong survival,” Sartor said. “In this case, two life-prolonging therapies are compared to one another in a phase III trial for the first time.”

The FIRSTANA trial included 1,168 patients randomized to one of three groups: cabazitaxel 20 mg/m2 (389 patients), cabazitaxel 25 mg/m2 (388 patients), or docetaxel (391 patients). All patients also received prednisone. Patients had received no prior chemotherapy and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; the demographics were well-balanced between groups. Sartor noted that very few patients had received prior enzalutamide or abiraterone.

The OS was no different between the three groups. The median OS in the docetaxel group was 24.3 months, compared with 24.5 months with cabazitaxel 20 mg and 25.2 months with the 25-mg dose. The hazard ratio (HR) for the 20-mg group compared with docetaxel was 1.009 (95% CI, 0.85–1.197; P = .9967). For the 25-mg group compared with docetaxel, the HR was 0.97 (95% CI, 0.819–1.16; P = .7574).

PFS was also very similar, at 5.3 months for docetaxel, 4.4 months for the 20-mg dose, and 5.1 months for the 25-mg dose. The HRs again showed no differences. The tumor response rate with the 25-mg dose was 41.6%, which was significantly better than the 30.9% with docetaxel (P = .0370), but Sartor said that likely doesn’t have much clinical significance.

Almost all patients experienced treatment-emergent adverse events of any grade. There were more serious events in the 25-mg group (47.6%) than in the 20-mg group (34.4%) and in the docetaxel group (32.6%). There were some differences in specific adverse event incidence, such as a higher rate of hematuria with cabazitaxel, and a higher incidence of peripheral sensory neuropathy with docetaxel. Most of the deaths that occurred in the trial were due to disease progression.

The discussant for the session, Derek Raghavan, MD, PhD, of the Levine Cancer Institute in Charlotte, North Carolina, said that the similarity in outcomes suggests docetaxel should remain the first therapy used in these patients. “There’s no indication that I can see for using cabazitaxel front-line,” he said.