The 10th Genitourinary Cancers Symposium, sponsored by ASCO, the American Society for Radiation Oncology, and the Society of Urologic Oncology, was held January 29–February 1, 2014, in San Francisco. The more than 630 abstracts presented addressed essential research in genitourinary malignancies, including data on some of the newest, most cutting-edge treatments available.
Several papers stand out in my mind as important, possibly groundbreaking, and may alter the approach to treating genitourinary malignancies. The five following abstracts were among the most noteworthy.
Enzalutamide for Chemotherapy-Naive Prostate Cancer
Abstract LBA1. Beer TM, Armstrong AJ, Sternberg CN, et al: Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): Results of phase III PREVAIL study.
The authors performed a randomized, double-blind, placebo-controlled phase III (PREVAIL) study in patients with metastatic castration-resistant prostate cancer. The patients were either asymptomatic or mildly symptomatic. They received enzalutamide (Xtandi), an androgen-receptor blocker (160 mg/d) or placebo, and had never received any other chemotherapy.
A total of 1,717 men (1,715 treated) were randomly assigned to the two arms between September 2010 and September 2012. The investigators found a 29% reduction in deaths in the enzalutamide group compared to the placebo group, and an 81% reduction in disease progression. The two primary endpoints in this trial were overall survival and radiographic progression-free survival.
Enzalutamide treatment resulted in 20% complete responses and 39% partial responses, compared with a 5% objective response rate in the placebo arm. Enzalutamide also significantly delayed the need for chemotherapy. On average, patients receiving enzalutamide needed chemotherapy 17 months later than those in the placebo arm.
The Independent Data Monitoring Committee deemed the benefit-risk ratio to favor enzalutamide and recommended stopping the study and allowing placebo patients to cross over to enzalutamide. The authors concluded, “Treatment with enzalutamide significantly improves overall survival and radiographic progression-free survival in men with chemotherapy-naive metastatic castration-resistant prostate cancer.”
Radium-223 Improves Survival in Prostate Cancer
Abstract 9. Nilsson S, Vogelzang NJ, Sartor AO, et al: 1.5-year post-treatment follow-up of radium-223 dichloride (Ra-223) in patients with castration-resistant prostate cancer (CRPC) and bone metastases from the phase 3 ALSYMPCA study.
In follow-up to the ALSYMPCA study of radium Ra 223 dichloride (Xofigo), the first alpha-emitting pharmaceutical approved by the U.S. Food and Drug Administration for treatment of patients with castration-resistant prostate cancer with symptomatic bone metastases, the investigators found the agent significantly improved overall survival by 3.6 months vs placebo.
They concluded, “Ra-223 is an effective and well-tolerated treatment for castration-resistant prostate cancer with symptomatic bone metastases. No major safety issues were identified within ~1.5 years after treatment in the ALSYMPCA safety population.”
Role of Total Androgen Blockade in Prostate Cancer
Abstract 4. Fossa SD, Widmark A, Klepp OH, et al: Ten- and 15-year prostate cancer-specific survival in patients with nonmetastatic high-risk prostate cancer randomized to lifelong hormone treatment alone or combined with radiotherapy (SPCG VII).
This important Scandinavian trial, a follow-up to previous study of the same group of patients [Widmark et al: Lancet 373:301-308, 2009], demonstrated a significant reduction in prostate cancer–specific mortality among patients with locally advanced or histologically aggressive prostate cancer who received total androgen blockade followed by radiotherapy and continuous antiandrogen therapy compared to patients given hormonal treatment only. Patients in the total androgen blockade arm had a 12% reduction in deaths. The patients were followed for a median of 10.7 years.
The abstract data are quite convincing. Among the 439 men receiving hormone therapy only, 118 died of prostate cancer, whereas of the 436 receiving combination therapy, only 45 died. For the patients receiving androgen ablation alone, cancer-specific mortality at 10 and 15 years was 18.9% and 30.7%. Patients receiving both radiotherapy and androgen ablation had a 10- and 15-year prostate cancer-specific mortality of 8.3% and 12.4%, respectively.
The authors concluded, “Addition of local radiotherapy to hormonal treatment in patients with non-metastatic locally advanced or high-risk prostate cancer more than halved the 10 and 15 year prostate cancer-specific mortality and substantially decreased overall mortality.”
Impact of Angiotensin System Inhibitors on Renal Cell Cancer Outcomes
Abstract 437. McKay RR, Rodriguez GE, Lin X, et al: Impact of angiotensin system inhibitors (ASI) on outcomes in patients with metastatic renal cell carcinoma (mRCC): Results from a pooled clinical trials database.
Treatment of metastatic renal cell carcinoma has been the focus of intense research using new and exciting vascular endothelial growth factor (VEGF)-targeted agents such as sunitinib (Sutent), sorafenib (Nexavar), axitinib (Inlyta), bevacizumab (Avastin); mammalian target of rapamycin (mTOR)-targeted agents such as temsirolimus (Torisel); and interferon alfa. At the same time, however, accumulating evidence has implicated common antihypertensive angiotensin system inhibitors (angiotensin-converting enzyme inhibitors and angiotension-receptor blockers such as lisinopril, captopril, and losartan) in the modulation of angiogenesis and tumorigenesis. The authors of this important retrospective study evaluated the role of these medications in the survival outcomes of patients with metastatic renal cell carcinoma.
The study evaluated the mortality outcomes of 4,736 patients on one or a combination of the above-mentioned targeted therapy medications, also treated with an angiotensin system inhibitor (n = 1,383) or without additional angiotensin system inhibitor treatment (n = 3,353).
The overall survival for patients receiving angiotensin system inhibitors was 27 months, compared with 17 months for those not using these agents. In addition, cancer was more likely to shrink in patients taking angiotensin system inhibitors. The researchers also analyzed data from patients taking any type of antihypertensive agent (n = 2,000) and found that overall survival for patients using angiotensin system inhibitors was 27 months compared to 18 months for those on other types of antihypertensive agents.
The authors stated, “Angiotensin system inhibitor use was associated with improved progression-free survival and overall survival when compared to patients who did not receive an angiotensin system inhibitor. This association was retained in multivariable analysis adjusted for age, gender, presence of bone metastases, and risk groups…. This is the largest retrospective study to date evaluating the role of angiotensin system inhibitors on outcomes in cancer patients. In this analysis, we demonstrate that concomitant use of angiotensin system inhibitors may improve survival outcomes in patients with metastatic renal cell carcinoma treated in the era of targeted therapy.”
Prognostic Model for Renal Cell Carcinoma
Abstract 398. Ko JJ, Xie W, Heng DY, et al: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model as a prognostic tool in metastatic renal cell carcinoma (mRCC) patients previously treated with first-line targeted therapy (TT).
Prognostic models may be very helpful to both patients and oncologists in the treatment of any disease, especially in metastatic renal carcinoma. The authors of this international study sought to validate the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in predicting the value of second-line targeted therapy in patients with disease progression on first-line targeted therapy.
Their study included 1,021 patients on second-line targeted therapy in 19 international centers. The IMDC identified five (of six) predefined factors (anemia, thrombocytopenia, neutrophilia, Karnofsky performance status less than 80%, and interval less than 1 year from diagnosis to treatment), measured at the time of second-line targeted therapy, as independent predictors of poorer overall survival. The sixth predefined factor, hypercalcemia, was not a statistically significant predictor in multivariable analysis.
The authors concluded, “The IMDC prognostic model has been validated in and can be applied to patients previously treated with targeted therapy, in addition to previously validated populations in first-line targeted therapy and non-clear cell setting.”