TOKYO, NEW YORK & ALAMEDA, Calif.—Castration-resistant prostate cancer, as defined by the National Cancer Institute, is a type of prostate cancer “that keeps growing even when the amount of testosterone in the body is reduced to very low levels. Many early-stage prostate cancers need normal levels of testosterone to grow, but castrate-resistant prostate cancers do not.” In this type of cancer, even if there is no detectable metastasis, a rapid increase in prostate-specific antigen (PSA) can lead to the cancer becoming metastatic. Two different trials in castration-resistant prostate cancer—both metastatic and non-metastatic—have shown some success in addressing this cancer subtype, as announced this week.
Astellas Pharma Inc. and Pfizer Inc. are evaluating XTANDI (enzalutamide) plus androgen-deprivation therapy (ADT) vs. placebo plus ADT in the Phase 3 PROSPER trial in men with non-metastatic castration-resistant prostate cancer (nmCRPC). PROSPER is a randomized, double-blind, placebo-controlled trial that enrolled roughly 1,400 men with nmCRPC in several countries. Trial participants had prostate cancer that had progressed based on a rising PSA level despite ADT, but demonstrated no symptoms or present evidence of metastatic disease. The primary endpoint of the trial was metastasis-free survival, measured as the time from a patient entering the trial until the cancer was radiographically detected as having metastasized, or until death, within 112 days of treatment discontinuation. Secondary endpoints included overall survival, time to PSA progression and time to first use of antineoplastic therapy.
The companies announced that the combination of XTANDI and ADT resulted in a statistically significant improvement in overall survival in patients with nmCRPC. A preliminary analysis seems to show that adverse events were generally consistent with those previously seen in the trial, and further safety data will be shared in the final PROSPER analysis in the future.
This past December, the U.S. Food and Drug Administration approved Astellas' and Pfizer's supplemental New Drug Application for XTANDI as a treatment for men with metastatic castration-sensitive prostate cancer. In addition to that indication, XTANDI is also approved to treat non-metastatic and metastatic CRPC.
Metastatic CRPC is the focus of the second trial. Exelixis Inc. shared partial data from its metastatic CRPC cohort of COSMIC-021, with a full presentation to be made on Feb. 13 at the 2020 American Society of Clinical Oncology’s Genitourinary Cancers Symposium. The Phase 1b trial is evaluating the combination of cabozantinib (Cabometyx) and atezolizumab (Tecentriq) in patients with locally advanced or metastatic solid tumors.
This interim analysis featured 44 patients, with a median follow-up of 12.6 months. The objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1) was 32 percent, which included two complete responses and 12 partial responses, and disease control rate was 80 percent. Of the 36 patients with high-risk clinical features—including visceral metastases and/or extra-pelvic lymph node metastases, the overall response rate was 33 percent. Median duration of response for patients who responded to treatment was 8.3 months. Of the 12 patients who had an objective response and at least one post-baseline PSA evaluation, 67 percent saw a PSA decline of at least 50 percent.
“We’re happy to share these encouraging results from the metastatic CRPC cohort from COSMIC-021, our first trial evaluating the combination of cabozantinib and atezolizumab,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “We look forward to receiving data from the most recent expansion of this CRPC cohort while we are also preparing for the initiation of a Phase 3 pivotal trial in this indication. We are excited about the emerging data in metastatic CRPC and elsewhere, and the potential of combining cabozantinib with immunotherapies in this and other difficult-to-treat tumor types.”
On Jan. 7, Exelixis announced that the metastatic CRPC cohort 6 of the trial had been expanded to enroll up to 130 patients. Should the existing and expanded CRPC cohorts support it, and pending regulatory approval from the FDA, the company plans to file for accelerated approval in a metastatic CRPC indication as early as next year.