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ASCO 2013 Report: Genitourinary Cancer

Meeting Report |
June 17, 2013

ASCO 2013 Report: Genitourinary Cancer

  1. Robert Dreicer, MD, MS, FACPAU1254

Highlights of the latest research in renal, germ-cell, and prostate cancers

  1. Robert Dreicer, MD, MS, FACPAU1254

At this year's annual meeting of the American Society of Clinical Oncology (ASCO 2013), held May 31 through June 5 in Chicago, specialists discussed the latest findings in cancer research. The editors of Journal Watch Oncology and Hematology were in attendance to report highlights of the conference. Here, Dr, Robert Dreicer reviews new treatments for genitourinary cancers.

Sequential Sunitinib and Everolimus for Metastatic Renal Cancer

Sequential therapy for patients with good- or intermediate-risk metastatic renal cancer involves the use of a vascular endothelial growth factor receptor (VEGFR)–targeted tyrosine kinase inhibitor (TKI) followed by a mammalian target of rapamycin (mTOR) inhibitor, typically the oral agent everolimus.

To test whether this is the most effective sequence in which to administer these agents, Motzer and colleagues conducted a manufacturer-sponsored, phase II, randomized trial [Abstract 4504] comparing the standard dose and schedule of the TKI sunitinib followed at time of progression by the mTOR inhibitor everolimus (10 mg/day) versus the reverse order of everolimus followed by sunitinib. The study involved 471 treatment-naive patients with good- or intermediate-risk metastatic renal cell cancer (85% with clear-cell disease). At time of progression, patients crossed over and continued on the alternate drug until further progression. The primary endpoint was progression-free survival (PFS) noninferiority of first-line everolimus to first-line sunitinib. Secondary endpoints were overall survival (OS), combined first-line and second-line PFS, and safety.

At median follow-up of 2 years, patients initially treated with sunitinib or everolimus had median PFS of 10.71 and 7.85 months, respectively; thus, noninferiority of first-line everolimus was not achieved. Moreover, the combined PFS and OS of sunitinib followed by everolimus was 25.8 and 32.3 months, respectively, whereas the combined PFS and OS of everolimus followed by sunitinib was 21.1 and 22.4 months. The toxicity observed was as expected for these agents.

The authors concluded that a standard treatment paradigm of front-line sunitinib followed by everolimus at progression should remain. By extension, one should include other approved TKIs such as pazopanib or sorafenib as initial therapy. Unaddressed in this study is the comparative utility of using a second TKI versus an mTOR inhibitor in the second-line setting.

Active Surveillance Effective for Patients with Stage I Nonseminoma

Current management of patients with stage I nonseminomatous germ-cell tumors (NSGCTs) includes consideration of retroperitoneal node dissection, adjuvant chemotherapy, and active surveillance. To gain further insights into the role of active surveillance, Kollmannsberger and international colleagues pooled large institutional databases to retrospectively analyze 1034 patients with clinical stage I NSGCT managed with active surveillance from 1999 to 2009 [Abstract 4503]. Of these patients, 220 had evidence of lymphovascular invasion (LVI+) and 220 were negative for lymphovascular invasion (LVI–).

During a median follow-up of 63 months, 221 relapses occurred (21%); median time to relapse, 6 months. A total of 48% of LVI+ patients relapsed versus 14% of LVI– patients. Essentially, all patients relapsed with good- or intermediate-risk disease. Regardless of LVI status, testicular cancer–specific survival was 99%, and 98% of patients were alive without evidence of disease. The authors concluded that active surveillance is a safe and effective management strategy for all patients with stage I NSGCT.

This retrospective study with a relatively recent data set confirms that active surveillance is most appropriate for stage I NSGCT patients if there is reasonable certainty of adherence. The vast majority of patients who relapsed did so within 2 years; most had good- or intermediate-risk disease and were cured at a very high rate.

Bone-Targeted Therapy Plus Docetaxel for Prostate Cancer

Advanced prostate cancer is a highly bone-tropic neoplasm. Strontium-89 (Sr89), a beta-emitting radiopharmaceutical, has demonstrated utility as a palliative agent for patients with advanced disease, and zolendronic acid (ZA), a bisphosphonate, has been shown to decrease skeletal-related events (SREs). Now James and U.K. colleagues have conducted a factorial randomized controlled trial [Abstract LBA5000] to evaluate the clinical utility of combining these agents with docetaxel in 757 patients with castrate-refractory prostate cancer metastatic to bone. Of these patients, 45% had received prior palliative radiotherapy; the median prostate-specific antigen (PSA) level was 144.

Patients were randomized to receive 6 cycles of docetaxel plus steroids alone or with zolendronic acid, a single dose of Sr89 after cycle 6, or both. Primary outcomes were clinical progression-free survival, pain progression, SRE, or death. Of note, no mandated radiologic assessments were included in this protocol.

No meaningful differences in overall survival were observed from adding either SR89 or zolendronic acid to docetaxel. However, SRE-free progression was significantly longer in patients receiving zolendronic acid plus docetaxel versus docetaxel alone (18.1 vs. 13.1 months; P=0.008).

These results provide evidence of the utility of zolendronic acid in patients receiving docetaxel and limited utility of Sr89 combination therapy. In an accompanying discussion, a recent change in the definition of skeletal issues proposed by the FDA was reviewed. Now termed symptomatic skeletal events (SSEs), these include external beam radiation for skeletal symptoms, symptomatic pathologic fracture, spinal cord compression, and tumor-related orthopedic surgical intervention, thus removing asymptomatic changes on x-ray imaging from the previous definition of SRE.

  • Disclosures for Robert Dreicer, MD, MS, FACP at time of publication Consultant / Advisory board Dendreon; Eli-Lilly; Endo Pharmaceuticals; Ferring; Janssen; Millennium; Novartis Speaker's bureau Janssen Editorial boards Urology Leadership positions in professional societies National Cancer Institute (Co-Chair, GU Oncology Steering Committee)

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