NEW DATA FOR M0-CRPC AND ADJUVNANT THERAPY FOR BLADDER CANCER

While many investigators still prefer to present their research at the ASCO Annual Meeting, more and more are choosing to present impactful data at subspecialty meetings. This was certainly true at the 2018 Genitourinary Cancers Symposium, held February 8-10 in San Francisco. Trials presented in the relatively common situation of M0 prostate cancer as well as the less common upper urinary tract malignancies may change daily practice.

M0 Prostate Cancer 

Castration resistance in the form of a rising prostate-specific antigen (PSA) during androgen deprivation therapy (ADT) is not at all unusual. When no radiographic signs of metastatic disease can be found, the cancer is still classified as M0. Deciding when to intervene in these men can be difficult. The current practice is to wait until clear radiographic signs of metastasis are found. Previous analyses have shown that PSA doubling time can predict when these radiographic signs will arise. A PSA doubling time of less than 6-10 months may be associated with radiographic metastases arising within 9 months or less. Two trials presented at this meeting looked at the effects of intervening in this situation.

The PROSPER trial^[1] looked at whether treating this population with enzalutamide would have an effect. A total of 1401 men with a PSA doubling time of 10 months or less were randomly assigned in a 2:1 ratio to receive either enzalutamide or placebo. The primary endpoint of the trial was metastasis-free survival. The addition of enzalutamide prolonged this endpoint from 14.7 months to 36.6 months, a nearly 2.5-times improvement. Time to PSA progression lengthened from 3.9 months to 37.2 months, and time to first use of a new therapy increased from 17.7 months to 39.6 months.

The SPARTAN trial^[2] also looked at this group of men but compared a new therapy, apalutamide, with placebo. Metastasis-free survival was again the primary endpoint. In this trial, the time to radiographic metastasis increased from 16.6 months in men receiving placebo to 40.5 months in men receiving this new agent. Time to PSA progression was 3.7 months in men receiving placebo and had not been reached in men receiving apalutamide.

The PROSPER and SPARTAN trial results were very impressive, but these studies had a less commonly described endpoint. The use of metastasis-free survival allowed the investigators to have reportable results in a reasonable length of time. The relatively short follow-up time in both of these trials means that overall survival data (a secondary endpoint in both trials) are too immature to show significant results. As a result of the primary endpoint data being so strongly positive, on February 14, the US Food and Drug Administration, following a priority review, approved apalutamide.^[3] There has also been discussion that an indication for enzalutamide in this population will be sought as well.

Adjuvant Chemo for Bladder Cancer 

Patients with muscle-invasive bladder cancer have been shown to benefit from neoadjuvant chemotherapy. For many years, trials of adjuvant chemotherapy were attempted in this group but somehow could not be completed successfully. As a result, strong data showing the benefit of adjuvant chemotherapy (as opposed to neoadjuvant therapy) do not exist in bladder cancer. Primary cancers of the upper urothelial tract are much less common but are often treated similarly to lower tract cancers. Investigators at this meeting presented the results of the POUT trial,^[4]which included 261 patients with primary cancers of the upper urothelial tract. Following surgery, patients were randomly assigned to either surveillance or four cycles of gemcitabine and either cisplatin or carboplatin (depending on renal function). The primary endpoint of the trial was 3-year disease-free survival. At an interim analysis with median follow-up of 19 months, the early stopping criteria were met and the trial was halted. The primary endpoint of 3-year disease-free survival was 71% in those patients receiving adjuvant chemotherapy as opposed to 54% in those not receiving chemotherapy. This translated to a hazard ratio of 0.49 with a P value of .001. Better results were seen among patients with N0 disease, patients with clear margins, and those receiving cisplatin as opposed to carboplatin. Overall survival data are immature, but early separation in the curves has occurred.

These trials, along with other presentations, make it clear that the Genitourinary Symposium specialty meeting is gaining in importance. It may never have the impact of the ASCO Annual Meeting, but it can no longer be ignored.