The novel agent MDV3100 prolonged survival in men with castration- resistant prostate cancer (CRPC) who progressed on treatment with docetaxel, according to results of the large phase 3 AFFIRM trial reported at the 2012 American Society of Clinical Oncology Genitourinary Cancers Symposium held in San Francisco, California.
The trial was halted early by an Independent Data Monitoring Committee in November 2011 due to the obvious survival benefit of MDV3100, and men in the placebo group were offered MDV3100 treatment. Results reported were based on interim results leading to the trial’s discontinuation.
“MDV3100 significantly and meaningfully prolonged survival by nearly 5 months in men with late-stage prostate cancer. Secondary measures of time to progression and response were all consistent with the survival benefit. The drug was well tolerated. The favorable benefit:risk ratio will likely position MDV3100 as the frontline agent in the post-docetaxel setting,” stated Howard Scher, MD, Memorial Sloan-Kettering Cancer Center, New York City.
MDV3100 is a first-in-class, oral investigational agent designed to target and inhibit androgen receptor signaling, which is a major driver of prostate cancer growth. The randomized, double-blind, placebo-controlled, multinational AFFIRM trial enrolled 1199 men with late-stage CRPC in whom docetaxel chemotherapy failed. They were randomized 2:1 to treatment with MDV3100 160 mg/day versus matched placebo.
MDV3100 achieved a median overall survival of 18.4 months versus 13.6 months for placebo, reflecting a highly significant 37% reduction in risk of death (P <.0001).
The survival benefits were supported by secondary outcome measures. A significantly higher proportion of patients in the MDV3100 arm demonstrated evidence of tumor shrinkage on CT or MRI imaging (soft tissue response on imaging 28.9% for MDV3100 vs 3.8% for placebo; P <.0001). Additionally, significantly more men treated with the androgen receptor signaling inhibitor had declines of 50% or greater in prostate-specific antigen (PSA) levels from baseline versus placebo patients (54% vs 1.5%, respectively; P <.0001). Median time to confirmed PSA progression was 8.3 months for MDV3100 versus 3 months for placebo (P <.0001).
MDV3100 had exceptionally good tolerability in this compromised group of patients. A similar percentage of men experienced adverse events: 98.1% in the MDV3100 group and 97.7% in the placebo group. More serious adverse events were reported in the placebo group: 45.3% for MDV3100 and 53.1% for placebo. Further, more drug discontinuations due to adverse events were reported in the placebo group (7.6% and 9.8%, respectively), and more adverse events led to death in placebo patients (2.9% and 3.5%, respectively).
Scher said that it is unusual for placebo patients to experience more serious adverse events than treated patients.
MDV3100 joins the list of drugs known to extend survival in CRPC. These positive results were greeted with much enthusiasm. Press Cast moderator, Nicholas Vogelzang, MD, said: “I have just one word: Wow!” Vogelzang went on to say this drug will be studied earlier in the course of disease and in sequence or combination with other drugs known to improve survival in CRPC.