Reduced-dose cabazitaxel is non-inferior to the standard dose for patients with metastatic castration-resistant prostate cancer (mCRPC) who previously received docetaxel, according to results of the PROSELICA (ClinicalTrials.gov Identifier: NCT01308580) study.1
The lesser toxicity of the 20 mg/m2 (C20) dose compared with the 25 mg/m2 (C25) dose may benefit frail patients in particular, or those with poor functional status.
“The PROSELICA study confirmed the observations of a prior study that cabazitaxel is an active drug for prostate cancer. The study showed that, if you decrease the dose from 25 to 20 mg/m2, that treatment remains active,” said lead author Mario Eisenberger, MD, R. Dale Hughes professor of oncology and urology at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland.
Since 2004, docetaxel has been recommended as a first-line chemotherapy for men with mCRPC, based on the finding that it improves overall survival (OS) compared with mitoxantrone.2 Yet men with mCRPC who progress or cannot tolerate first-line docetaxel have limited options.
For these patients, cabazitaxel, a semi-synthetic taxane derivative in clinical use since 2010, offers an effective option. Although cabazitaxel may prolong OS vs mitoxantrone, a trade-off is a greater number of severe adverse events (AEs), a higher death rate related to sepsis, and renal failure.3,4 Nonetheless, it is recommended over mitoxantrone in the second-line setting for men with mCRPC.
The FIRSTANA (ClinicalTrials.gov Identifier: NCT01308567) study, which evaluated C20 and C25 vs docetaxel as first-line therapy with a primary endpoint of OS, concluded that either dose was as effective as docetaxel (OS = 24.5, 25.2, and 24.3 months, respectively). AEs occurred most often with C25, though the types of AEs differed. Febrile neutropenia, diarrhea, and hematuria were more frequent with C25, while peripheral neuropathy, peripheral edema, alopecia, and nail disorders were more frequent with docetaxel.5
For PROSELICA, researchers enrolled men from 22 countries with prostate adenocarcinoma, evidence of progression on androgen-deprivation therapy, and previous docetaxel treatment. Patients previously treated with mitoxantrone, cabazitaxel, or radiopharmaceuticals, or who had persistent grade 2 or worse adverse events on previous therapy were excluded.
Of 1200 patients (intent-to-treat [ITT] population) randomly assigned to receive C20 plus 10 mg prednisone or C25 plus 10 mg prednisone, 1175 received treatment (safety population). The per-protocol population included 489 men who received C20 and 498 who received C25. Most patients had rising prostate-specific antigen (PSA) levels at study entry. More than 8 in 10 had received prior chemotherapy with docetaxel, almost half of each group had received multiple hormonal therapy regimens, and a quarter of each group had received prior abiraterone.
Median OS was 13.4 months with C20 and 14.5 months with C25 in the ITT population, for a hazard ratio of 1.024 (95% CI, 0.922-1.184). The upper boundary of the HR was within the predefined upper boundary for non-inferiority, demonstrating that C20 was an effective mCRPC treatment.
But results on several secondary endpoints favored treatment with the higher dose.
A significantly higher proportion of patients achieved at least 50% reduction in PSA with C25 (P <.001), and treatment with C20 was associated with a significantly higher risk of PSA progression (HR = 1.195, 95% CI: 1.025-1.393). In the subgroup analyses, trends favoring C25 were seen in patients previously treated with abiraterone, and those with bone progression or lactate hydrogenase levels greater than 500 IU/L at baseline.