Docetaxel rechallenge was tied to improved overall survival compared with cabazitaxel in men with metastatic castration-resistant prostate cancer (mCRPC) who did not experience disease progression on prior docetaxel treatment, according to findings from a retrospective cohort study.

The analysis also highlighted the “markedly greater” cost of cabazitaxel compared with generic docetaxel. According to drug pricing data from Veterans Affairs (VA), a six-cycle course of cabazitaxel can cost tens of thousands of dollars, while generic docetaxel may come to less than $100.

“Docetaxel rechallenge may offer a tolerable, lower-cost option for patients previously responsive to taxane therapy,” lead author Pedro C. Barata, MD, of Case Western Reserve University School of Medicine in Cleveland, and colleagues wrote.

The study was published online on January 16 in JAMA Network Open.

Several new and expensive agents have appeared on the market since docetaxel was established as the mainstay chemotherapy option for mCRPC two decades ago. But the best treatment for men who discontinue docetaxel for reasons other than disease progression remains unclear.

Given that randomized trials in this select patient group are unlikely, the researchers undertook a retrospective cohort study evaluating patient outcomes in the nationwide VA healthcare system.

Overall, 3123 patients received at least three cycles of initial docetaxel treatment after being diagnosed with mCRPC. Of these, 669 patients met the study’s inclusion criteria, with 407 receiving cabazitaxel and 262 receiving docetaxel rechallenge. The median number of cycles of initial docetaxel treatment was 6 in both groups.

Docetaxel rechallenge was associated with significantly longer overall survival (12.3 vs 9.6 months; hazard ratio, 0.81; 95% CI, 0.55-0.99) after adjusting for patient characteristics.

“Although the absolute survival difference of approximately 2.7 months appears modest, this magnitude is comparable to other meaningful gains seen in mCRPC,” Barata and colleagues said.

Patients receiving docetaxel rechallenge also demonstrated greater reductions in PSA and a longer time to subsequent systemic treatments or death, which was 10.7 vs 8.9 months in the docetaxel rechallenge vs cabazitaxel groups.

Additionally, the economic implications of this treatment choice “are substantial,” according to Divya A. Parikh, MD, of Stanford University, Stanford, and the VA Palo Alto Health Care System, Palo Alto, California, and colleagues, writing in an accompanying editorial.

While the cost of these drugs in the US can vary significantly, pricing data from the VA indicate that a six-cycle course of cabazitaxel (20 mg/m²) costs nearly $54,000 vs $85 for generic docetaxel (75 mg/m²).

“Rechallenge with docetaxel in appropriately selected patients represents a cost-conscious alternative that aligns with the principles of efficient resource utilization without compromising patient outcomes,” the editorialists noted.

The study authors acknowledged some study limitations, namely the possibility of residual confounding for certain unmeasured confounders. Data on symptom burden, tumor genomics, and chemotherapy dosing, for instance, were not available.

Urban Emmenegger, MD, medical oncologist who was not involved in the research, agreed about possible residual confounding in the study, in particular the type of systemic prostate cancer drugs given before, between, or after the two taxane therapies.

Emmenegger also pointed out that cost considerations may be different outside of the US, where more affordable generic versions of cabazitaxel are available. Although the FDA has approved generic versions of cabazitaxel, they’re not widely available, partly due to ongoing patent disputes that have delayed market entry.

Overall, “I do not regard docetaxel rechallenge as a competitor for cabazitaxel,” explained Emmenegger, of Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada. The “aim is to provide my patients with as many lines of therapy as possible (eg, docetaxel->docetaxel rechallenge->cabazitaxel).”

This study had no commercial funding. Barata reported receiving personal fees from Astellas Pharma Inc, Bayer AG, AstraZeneca, Pfizer Inc, Johnson & Johnson, and others. Other study authors reported having relevant disclosures. Emmenegger and the editorialists reported having no relevant disclosures.