Research Highlights from the 2016 Genitourinary Cancers Symposium

Apr 26, 2016

The 2016 Genitourinary (GU) Cancers Symposium, held in San Francisco in January, brought together over 3,300 urologists, surgeons, radiation oncologists, medical oncologists, pathologists, and other members of the cancer care community. With cosponsorship from ASCO, the American Society for Radiation Oncology, and the Society of Urologic Oncology, the Symposium featured studies selected from nearly 650 abstracts submitted by researchers from North America, Europe, Asia, and other regions. The theme of this year’s meeting, “Patient- Centric Care: Translating Research to Results,” focused on practical implementation of new therapeutic strategies informed by basic and translational research as well as on emerging translational research that will drive additional therapeutic innovation in the future.

Prostate Cancer

Two large, randomized, phase III noninferiority studies conducted in men with localized prostate cancer—the Radiation Therapy Oncology Group (RTOG) trial RTOG 0415 and the CHHiP (CRUK/06/016) trial—demonstrated that hypofractionated delivery of radiation therapy (RT) provides greater patient convenience without major sacrifices in efficacy or tolerability (Abstracts 1 and 2). RTOG 0415, conducted in the United States in more than 1,100 men with low-risk disease, established that hypofractionated delivery of 70 Gy in 28 fractions over 5.6 weeks is noninferior to conventional delivery of 73.8 Gy in 41 fractions over 8.2 weeks, shaving off 2.6 weeks of treatment time, albeit with a small increase in grade 2 GU and gastrointestinal late toxicities. Similarly, CHHiP, conducted in the United Kingdom in 3,216 men with primarily intermediate-risk prostate cancer, demonstrated that a hypofractionated RT regimen of 60 Gy delivered in 20 fractions, which provided radiation in roughly half the time of a conventional RT schedule of 74 Gy delivered in 37 fractions (4.0 weeks vs. 7.4 weeks), produced comparable efficacy and near-comparable toxicity outcomes.

The 10-year results from the RTOG 9601 trial confirmed that adding 24 months of antiandrogen therapy (AAT) to RT in men with prostate cancer who required salvage after radical prostatectomy prolonged survival and reduced the incidence of prostate cancer-related metastasis and death compared with RT alone—without causing undue toxicity (Abstract 3). The patients most likely to benefit from the addition of AAT included men with adverse prognostic features: namely, those with Gleason scores ranging from 7 to 10, entry prostate- specific antigen values of 0.7 to 4.0 ng/mL, or positive surgical margins.

Penile, Urethral, and Testicular Cancers

A retrospective study revealed that patients with metastatic testicular germ cell tumors (GCTs) who survive and remain disease-free for greater than 2 years have an excellent probability of staying alive and disease-free in subsequent years (Abstract 472). For example, among the 16% of patients with poor-risk disease, the probability of surviving an additional 2 years after initial diagnosis was 71%. However, for those men who survived 12, 24, and 36 months after treatment, the probability of surviving an additional 2 years steadily increased to 80%, 93%, and 97%, respectively. The findings support less frequent surveillance imaging post-treatment and the need to update the 1997 International Germ Cell Cancer Collaborative Group risk classification findings.

Researchers demonstrated that use of the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay that examines cancer-related genes singled out 51 potentially actionable alterations in nearly half of 76 patients harboring platinum-resistant advanced GCTs (Abstract 473). These alterations include receptor tyrosine kinases and proteins in the TP53, Ras, PI3K/mTOR, and WNT pathways. Applying this technology in the clinic may someday guide individualized treatment selection in a significant proportion of patients with resistant advanced GCT.

Urothelial Carcinoma

According to new data from the IMvigor 210 trial conducted in 429 patients with locally advanced or metastatic urothelial carcinoma (UC) who were previously treated with platinum, the PD-L1 inhibitor atezolizumab yielded an overall response rate of 26% and a median overall survival (OS) of 11.4 months in patients with the highest levels of PD-L1 expression on immune cells (Abstract 355). In addition, a number of patients without response experienced stable disease, bumping the disease control rates up to 19% to 35% across PD-L1 subgroups, which suggests that atezolizumab may provide clinical benefit to a sizable proportion of patients who have no other viable treatment options. These findings are anticipated to lead to accelerated approval of atezolizumab for metastatic UC that has progressed after a prior platinum-based chemotherapy.

Renal Cell Carcinoma

In an update of the phase III CheckMate 025 trial conducted in 821 patients with advanced renal cell carcinoma (RCC) that progressed after prior antiangiogenic therapy, preplanned subgroup analyses showed that the survival and response benefits observed with nivolumab in the overall population also applied across a wide variety of patient subgroups (Abstract 498). Most notably, nivolumab edged out everolimus for survival improvement among the subgroup of patients who received one prior antiangiogenic therapy. Median OS in this subgroup reached 23.6 months with nivolumab versus 19.9 months with everolimus (HR 0.79, 95% CI [0.63, 0.99]), supporting the use of nivolumab as a second-line regimen after failure of antiangiogenic therapy.

An analysis of data from nearly 1,100 patients with metastatic RCC (mRCC) in the International mRCC Database Consortium revealed that the 19% who stopped first-line antiangiogenic therapy because of toxicity fared far better on second-line treatment than the 77% of patients who had to stop initial therapy because of progression (Abstract 503). Not only was the clinical benefit rate in the second-line setting improved in the former group (68% vs. 57%; adjusted odds ratio 1.58, 95% CI [1.07, 2.35]; p = 0.023), so too was OS (17.4 vs. 11.2 months; adjusted HR 0.69, 95% CI [0.56, 0.84]; p = 0.0002). These findings suggest that it may be important to stratify patients according to the reason for discontinuation of first-line antiangiogenic therapy in future mRCC clinical trials of second-line therapy.


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