Highlights from the 2015 Genitourinary Cancers Symposium

Apr 26, 2015

Nearly 3,000 attendees gathered at the 2015 Genitourinary (GU) Cancers Symposium, held on February 26-28 in Orlando, Florida, with the goal of exchanging ideas, best practices, and scientific research that will lead to future progress in GU cancers. Reflecting the meeting’s theme, “Integrating Biology into Patient-Centric Care,” this year’s sessions featured several key studies pulled from the more than 640 abstracts submitted by researchers from around the globe.

Adjuvant treatment of renal cell carcinoma

The data presentation causing the largest stir at the meeting was the report on the phase III ASSURE trial. The study was the first to evaluate the efficacy of multi-targeted VEGF inhibitors in the adjuvant setting for patients with locally advanced renal cell carcinoma at high risk of recurrence (Abstract 403). The results demonstrated that neither sorafenib nor sunitinib offered benefits above and beyond those of placebo in the adjuvant setting; time to disease recurrence after surgery reached 5.6 years with either sorafenib or sunitinib, as compared with 5.7 years with placebo. Using a stratified log-rank test, fiveyear disease-free survival (DFS) rates varied little across the three arms at 52.8% to 55.8%, yielding hazard ratios (HRs) of 0.98 for sorafenib and 1.01 for sunitinib in comparison with placebo. Similarly, five-year overall survival (OS) ranged little, from a low of 76.9% to a high of 80.7%, yielding HRs of 0.93 for sorafenib and 1.10 for sunitinib in comparison with placebo.

Prostate cancer: Detection and surveillance

The 4Kscore consists of a blood test that combines four kallikrein assays with important clinical information in an algorithm to determine a patient’s personalized probability of having high-grade cancer if a biopsy were to be performed. The first trial to prospectively evaluate the 4Kscore’s ability to identify high-grade prostate cancer among men in the United States found that the tool demonstrated accuracy (Abstract 1). Among 1,012 patients scheduled for a prostate biopsy who were included in the study, high-grade prostate cancer was identified in 231 (23%). The 4Kscore demonstrated better discrimination than the popular Prostate Cancer Prevention Trial Risk Calculator in predicting which men had high-grade prostate cancer (AUC [area under the curve] 0.82 vs. 0.74; p < 0.0001), thereby enabling clinicians to identify men likely to benefit from a prostate biopsy while sparing others from the invasive procedure.

Radiation therapy and hormone therapy for localized prostate cancer

The RTOG 0126 trial compared conventional versus dose-escalated radiation therapy (RT) in men with intermediate risk localized prostate cancer. The study found that among the nearly 1,500 evaluable patients included in the study, increasing the RT dose from 70.2 Gy to 79.2 Gy significantly decreased the 10-year rates of both biochemical failure according to the American Society for Radiation Oncology (ASTRO) definition (45% vs. 30%; p < 0.0001) and local disease progression (8% vs. 4%; p = 0.0059) (Abstract 4). Doseescalated RT significantly decreased the rate of distant metastases at 10 years compared with conventional RT (8% vs. 5%; p = 0.026). These improvements did come with a modest increase in late GU and gastrointestinal toxicities of grade 2 or higher, and the study failed to meet the primary endpoint of OS based on nearly identical 10-year survival rates (66% with 70.2 Gy vs. 67% with 79.2 Gy; p = 0.87).

Findings from the Prostate Cancer Study III showed that high-dose RT provides improved outcomes compared with standard-dose RT (Abstract 5). However, the trial also revealed the added benefit of a short course of androgen deprivation therapy (ADT). In this three-arm study, both arms that combined a six-month course of ADT with RT, whether it be 70 Gy or 76 Gy, excelled over high-dose RT alone. Based on median follow-up duration of 75.4 months, biochemical failure—one of the primary endpoints—occurred in 12.5% of patients who received short-term ADT plus low-dose RT, in 8.0% of patients who received short-term ADT plus high-dose RT, and in 21.5% of patients who received high-dose RT alone. DFS—the other primary endpoint— reached rates of 93.1%, 97.6%, and 86.3%, respectively, at five years.

A third related trial called ASCENDERT (Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy) pushed the treatment envelope even further by delivering higher RT doses via low-dose rate brachytherapy (LDR-B) and administering ADT for 12 months in patients with intermediate-/high-risk nonmetastatic prostate cancer (Abstract 3). The findings revealed that LDR-B resulted in a 50% reduction in the risk of biochemical relapse compared with an external beam conformal boost (DE-EBRT) in the context of ADT and pelvic EBRT— the first time this has been demonstrated in a randomized trial. The biochemical progression-free survival (PFS) rates for the LDR-B and DE-EBRT arms, respectively, were 88.7% versus 83.8% at five years, and 83.3% versus 62.4% at nine years. Notably, the trend favoring LDR-B over DE-EBRT for improved biochemical PFS held steady in both the intermediate-risk (seven year rates: 93.9% vs. 80.1%; p < 0.001) and high-risk (seven-year rates: 82.9% vs. 71.9%; p = 0.05) patient groups.

Commenting on this study, Daniel A. Hamstra, MD, PhD, of the University of Michigan Health System and Chair- Elect of the 2015 GU Cancers Symposium, said, “These results are potentially game changing... It’s the first level I evidence that we’ve had that brachytherapy provides a substantial improvement in disease control as compared to doseescalated EBRT.”

Systemic therapy for prostate cancer

Previous research tied androgen receptor splice variant 7 (AR-V7) to resistance to both enzalutamide and abiraterone in metastatic castration-resistant prostate cancer (mCRPC); the truncated form of AR-V7 lacks the ligand-binding domain targeted by androgen antagonists. In a new study, the presence of AR-V7 in circulating tumor cells did not correlate with primary resistance to taxane chemotherapy (Abstract 138). Among patients negative and positive for AR-V7 who received taxane, best prostate-specific antigen (PSA) response rates reached 65% and 41%, respectively, which did not differ significantly between arms (p = 0.194) in this small prospective study of 37 patients. PSA PFS and clinical/ radiographic PFS following taxane chemotherapy also turned out to be comparable between the AR-V7–negative and AR-V7–positive groups. Thus, these initial data suggest that AR-V7 may serve as a useful treatment selection marker in patients with mCRPC by indicating which patients may benefit from anti-androgens and which would fare better with taxane chemotherapy.

Results from the international phase III COMET-1 trial, which compared cabozantinib versus prednisone in patients with mCRPC previously treated with docetaxel and antiandrogens, also turned out negative, but with potential positive signals in select patient subgroups (Abstract 139). In the final analysis of the 1,028 patients who participated in the trial, median OS was 11.0 months with the anti-angiogenic agent versus 9.8 months with prednisone, a difference that did not reach statistical significance (HR 0.90, 95% CI [0.76, 1.06]; p = 0.213) (cabozantinib did yield significant improvements in the 12-week bone scan response, PFS, and time to the first skeletal-related event, among other endpoints, in comparison with prednisone).

To access complete Genitourinary Cancers Symposium Daily News coverage, visit gucasym.org/daily-news.

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