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An autologous dendritic cell-based immunotherapy (DCVAC/PCa) added to chemotherapy did not improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC), a phase III trial found.

Among over 1,100 men with mCRPC, median overall survival (OS) was 23.9 months in those who received DCVAC/PCa plus docetaxel-prednisone compared with 24.3 months for those who received placebo plus the chemotherapy (HR 1.04, 95% CI 0.90-1.21, P=0.60), reported Nicholas Vogelzang, MD, of the Comprehensive Cancer Centers of Nevada in Las Vegas, and colleagues.

There were also no differences observed for the secondary efficacy endpoints, including radiologic progression-free survival, time to prostate-specific antigen progression, or skeletal-related events, they noted in .

Post-hoc analyses of subgroups of patients who received different doses of DCVAC/PCa or placebo did show a trend in median OS suggestive of a treatment effect with increasing exposure:

• 10 or more doses: 31.5 months for DCVAC/PCa vs 27.0 months for placebo (HR 0.92, 95% CI 0.74-1.15, P=0.48)
• 12 or more doses: 35.9 vs 29.8 months, respectively (HR 0.77, 95% CI 0.60-1.00, P=0.05)
• 15 doses: 41.2 vs 38.7 months, respectively (HR 0.72, 95% CI 0.49-1.06, P=0.09)

An had shown that DCVAC/PCa combined with docetaxel resulted in a median OS of 19 months in patients with mCRPC -- superior to the predicted median OS of 11.8 months with the Halabi nomogram and 13 months with the Memorial Sloan Kettering Cancer Center nomogram.

Based on this prior trial, VIABLE was performed to test the hypothesis that combining DCVAC/PCa with docetaxel followed by maintenance therapy with DCVAC/PCa would improve OS in patients with mCRPC.

"The results of the VIABLE trial temper expectations for combination with docetaxel based on current technologies, but VIABLE also raises additional questions on the interplay of prior therapies and potential resistance patterns that may emerge," wrote Hiten D. Patel, MD, MPH, and Stephanie Berg, DO, of Loyola University Medical Center in Maywood, Illinois, in an .

"With several therapies now being used in the metastatic hormone-sensitive setting, determining the most appropriate sequence of these agents is a major challenge, and patients with mCRPC may have different biologic characteristics compared with those evaluated 20 years ago in traditional studies where the only prior therapy was androgen deprivation therapy or docetaxel," Patel and Berg added. "As the future of clinical trial design for mCRPC gets more complicated, acknowledging negative trials is important because they can spur thought and guide development that may ultimately lead us down more fruitful pathways to effective therapies."

VIABLE was conducted at 177 hospital clinics in the U.S. and Europe from June 2014 to November 2017, and included 1,182 men (median age 68) who were randomized 2:1 to receive DCVAC/PCa (n=787) or placebo (n=395), both in combination with docetaxel plus prednisone.

Since about two-thirds of patients had not received abiraterone or enzalutamide prior to the trial, Vogelzang and colleagues noted that "prior treatment status may act as an effect modifier."

They found no difference in median OS between the DCVAC/PCa and placebo groups among the 817 abiraterone- and enzalutamide-naive patients: 26.7 months versus 25.7 months (HR 0.94, 95% CI 0.78-1.13, P=0.50). Among the 365 patients pretreated with abiraterone and/or enzalutamide, the median OS was shorter in the DCVAC/PCa group: 16 months versus 21.0 months (HR 1.28, 95% CI 0.98-1.67, P=0.07).

These findings "may be attributed to the emergence of drug resistance after androgen receptor therapy," the authors suggested, and "provide a testable hypothesis for examining the interaction between prior abiraterone or enzalutamide exposure and the effects of DCVAC/PCa."

As for safety, treatment-emergent adverse events occurred in 9.2% of patients receiving DCVAC/PCa and 12.7% of those receiving placebo, with the most common being fatigue (36.2% vs 40.1%), alopecia (29.6% vs 34.3%), and diarrhea (27.5% vs 30.9%).

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