ASCO 2017 Report — Genitourinary Cancer

Meeting Report |
June 20, 2017

ASCO 2017 Report — Genitourinary Cancer

  1. Robert Dreicer, MD, MS, FACP, FASCO

Highlights of the latest treatments for urothelial, renal cell, germ cell, and prostate cancers

  1. Robert Dreicer, MD, MS, FACP, FASCO

At this year's annual meeting of the American Society of Clinical Oncology (ASCO 2017), held June 3 to 7 in Chicago, investigators discussed the latest findings in cancer research. The editors of NEJM Journal Watch Oncology and Hematology were on hand to report highlights of the conference. Here, Associate Editor Robert Dreicer, MD, MS, FACP, FASCO, reviews key presentations on new genitourinary cancer therapies. All meeting abstracts can be viewed in the ASCO meeting library).

Pembrolizumab for Cisplatin-Ineligible Advanced Urothelial Cancer

Until recently, therapeutic options for cisplatin-ineligible patients with advanced urothelial cancer were limited. Carboplatin-based chemotherapy has been considered a standard of care, and recently atezolizumab received FDA approval for this patient population.

O'Donnell and colleagues reported results from the Keynote-052 trial (abstract 4502), which evaluated the efficacy and safety of first-line therapy with the PD-L1 inhibitor pembrolizumab for 370 advanced urothelial cancer patients (median age, 74). All patients were deemed cisplatin-ineligible on the basis of renal function, performance status, grade 2 or higher neuropathy or hearing loss, or significant congestive heart failure.

Patients received standard-dose pembrolizumab every 3 weeks for 24 months or until disease progression or intolerable toxicity. The primary endpoint was objective response rate; secondary and exploratory endpoints included biomarker correlative studies.

At median follow-up of 9.5 months, the objective response rate was 29%, and the complete response rate was 7%. With longer follow-up, the response rate increased 5%. The median duration of response had not been reached.

This large phase II experience provides additional assurance regarding the activity and safety of checkpoint inhibitor therapy. With the level 1 evidence of a survival benefit demonstrated in the Keynote-045 trial, the role of pembrolizumab is firmly established as a standard of care in advanced urothelial cancer.

No Role for Pazopanib After Nephrectomy for Locally Advanced Renal Cell Cancer

The lack of a role for adjuvant tyrosine kinase inhibitor (TKI) therapy for locally advanced renal cancer seemed to have been settled by the large negative U.S. Intergroup ASSURE study (NEJM JW Oncol Hematol May 2016 and Lancet 2016; 387:2008). However, the more recent S-TRAC study (NEJM JW Oncol Hematol Dec 2016 and N Engl J Med 2016; 375:2246) suggested an improvement in disease-free survival (DFS) following 1 year of adjuvant sunitinib TKI therapy.

To test the efficacy and safety of the TKI pazopanib in this setting, Motzer and colleagues conducted an industry-sponsored, international, randomized study (PROTECT; abstract 4507), in which patients with locally advanced renal cancer received the drug or placebo for 1 year. Although initially designed and powered to treat patients at 800 mg/day, the study was amended after accrual of 403 patients to administer a starting dose of 600 mg/day, and an additional 1135 patients were accrued. The primary objective was amended to test the impact of 600 mg/day on DFS. Secondary objectives included quality of life and DFS of the entire patient population and those treated with 800 mg/day.

The primary objective of DFS in the 600 mg/day group was not met, and incidence of grade 3 or 4 toxicity was significantly greater with pazopanib than with placebo (60% vs. 21%). The investigators concluded that there is no role for pazopanib in the adjuvant setting. These results along with those of the ASSURE study suggest no routine role for adjuvant TKIs in locally advanced renal cancer.

PET Assessment of Residual Seminoma

The management of postchemotherapy masses in patients with seminoma has evolved following retrospective evidence of the utility of positron-emission tomography (PET) imaging in lesions >3 cm. Typically, patients with masses <3 cm would be managed expectantly with intermittent computed tomography (CT) assessment.

To provide additional insight into the utility of PET imaging in this setting, Cathomas and colleagues used a large germ cell registry to retrospectively study 91 patients with metastatic seminoma and residual PET-positive lesions after chemotherapy (abstract 4521).

At a median follow-up of 29 months, the median time from the last day of chemotherapy to PET imaging was 7 weeks. Post-PET management involved repeated imaging in 51% of patients, resection in 35%, biopsy in 10%, and radiotherapy in 4%. Histology of the resected specimen identified necrosis only in 25 cases (78%) and vital seminoma in 7 cases (22%). No biopsy revealed viable seminoma. This analysis demonstrated that PET-positive, postchemotherapy residual lesions were false-positive in about 75% of patients.

The utility of PET imaging for assessment of residual seminoma appears low. Therefore, routine CT scanning with most patients managed expectantly should be the standard of care.

Combination Therapy for Metastatic Prostate Cancer

Investigators for the STAMPEDE and LATITUDE studies showed that combining androgen-deprivation therapy (ADT) with abiraterone plus either prednisolone or prednisone significantly improved survival in men with metastatic disease and that this combination should be adopted as the standard of care (for complete summaries of these published studies, see NEJM JW Oncol Hematol Jul 2017 and N Engl J Med 2017 Jun 3 and 4; [e-pub]).

In the STAMPEDE study (abstract LBA5003), James and colleagues compared ADT alone or with abiraterone and prednisolone in 1917 patients with newly diagnosed, locally advanced, or metastatic disease who were starting ADT. At a median follow-up of 40 months, 3-year overall survival was significantly improved with combination therapy versus ADT alone, as was treatment-failure–free survival.

In the LATITUDE study (abstract LBA3), Fizazi and colleagues randomized 1199 patients with newly diagnosed, metastatic, castration-sensitive prostate cancer to receive ADT plus placebo or abiraterone and prednisone. At a median follow-up of 30.4 months, median OS was significantly longer in the abiraterone group than in the placebo group.

Editor Disclosures at Time of Publication

  • Disclosures for Robert Dreicer, MD, MS, FACP, FASCO at time of publication Consultant / Advisory board Medivation; Genentech/Roche; AstraZeneca; Bristol-Myers Squibb; Eisai; Exelixis; Asana Editorial boards Clinical Genitourinary Cancer; Current Urology Reports Leadership positions in professional societies National Cancer Institute (Co-Chair, GU Oncology Steering Committee); Bladder Cancer Advocacy Network (Member, Scientific Advisory Board)

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