Real-life survival with cabazitaxel shorter in FUJI vs TROPIC, PROSELICA

Treatment with cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC) results in a slightly lower median overall survival (OS) at 18 months as compared with that in the pivotal clinical trial, owing to the presence of features of poor prognosis at baseline and use of cabazitaxel in third line or beyond in 82 percent of patients, according to the FUJI study.

“There were no unexpected safety issues, with severe neutropaenia being the most important risk to consider when prescribing cabazitaxel,” the researchers said.

This multicentre, noninterventional cohort study included French mCRPC patients initiating cabazitaxel between 2013 and 2015. A total of 401 (median age, 70 years) patients were recruited in 42 centres and were followed for 18 months. The main metastatic sties were bones (87 percent), lymph nodes (42 percent) and visceral (20 percent).

Of the patients, 18 percent had cabazitaxel in second-line treatment, 39 percent in third-line and 43 percent in fourth-line or beyond. All of them received prior docetaxel, and 82 percent had prior abiraterone, enzalutamide or both.

Median duration of cabazitaxel treatment was 3.4 months, and median OS from initiation was 11.9 months (95 percent confidence interval, 10.1–12.9). [Br J Cancer 2019;doi:10.1038/s41416-019-0611-6]

Multivariate analyses revealed the association of grade ≥3 adverse events (AEs), visceral metastases, polymedication and >5 bone metastases with a shorter OS. The main grade ≥3 AEs were haematological with 8-percent febrile neutropaenia.

The median OS was shorter in this study (11.9 months) than in the phase III TROPIC trial (15.1 months) or in the PROSELICA trial (13.4 and 14.5 months for the initial cabazitaxel doses of 20 and 25 mg/m², respectively). [Lancet 2010;376:1147-1154; J Clin Oncol 35:3198-3206]

The researchers proposed two potential explanations for these differences: First, patients in the FUJI trial were older and more fragile than those enrolled in the clinical trials, where “severe eligibility criteria were applied.” Second, “patients with a very compromised status and short expected survival are often not included in clinical trials, whereas they are part of real-life observational studies.”

Data on cabazitaxel efficacy in everyday oncology practice were also available from the compassionate use programmes established in the Netherlands, Korea and Germany prior to the commercial availability of the said treatment.

The study from the Netherlands reported a median OS of 8.7 months (interquartile range [IQR], 6.0–15.9), which is closer to that seen in the present study and again shorter than that in TROPIC. [Clin Genitourin Cancer 2013;11:238-250e1]

The Korean study reported a longer median OS (16.5 months, 95 percent CI, 12.1–20.9), which is closer to that reported in TROPIC. On the other hand, the German study reported mean OS instead of median OS and is therefore not comparable. [Cancer Chemother Pharm 2014;74:1005-1013; Eur Urol 2013;63:977-982]

“The safety profile of cabazitaxel in FUJI was essentially similar to that observed in TROPIC or PROSELICA, and no unanticipated safety issues arose,” the researchers said.