New Agents and Combinations Targeting Genitourinary Cancers Presented at 2020 Symposium

February 14, 2020

Research from the 2020 Genitourinary (GU) Cancers Symposium highlights innovative new approaches for treating bladder, kidney, and prostate cancers. The studies will be presented at the Symposium, taking place February 13-15 at The Moscone West Building in San Francisco, California.

ASCO Perspective:
"Studies presented at the Symposium show that not only are new treatments that work in novel ways under development, but we're also combining existing treatments in new and more effective ways. Down the road, this research could translate to better survival with fewer side effects for patients with genitourinary cancers," said Sumanta K. Pal, MD, ASCO Expert in GU cancers.

Experts are available to comment on the studies below. Please contact the ASCO Media Team to schedule an interview with a study author or ASCO expert in GU cancers.

Patients With Locally Advanced or Metastatic Urothelial Carcinoma Show Durable Response to Enfortumab Vedotin Plus Pembrolizumab

Study Details: As of October 2019, 45 patients with locally advanced or metastatic urothelial carcinoma who were ineligible for platinum-based treatment received 1.25 mg/kg enfortumab vedotin (days 1 and 8) plus pembrolizumab (day 1). The primary endpoint was safety/tolerability.

Key Findings: The most common treatment-emergent adverse events were fatigue (58%, 11% at least grade 3), alopecia (53%), and peripheral sensory neuropathy (53%, 4% at least grade 3). One patient died due to an adverse event reported as related (multiple organ failure). Combination treatment with enfortumab vedotin plus pembrolizumab led to an objective response rate of 73% in patients with locally advanced or metastatic urothelial carcinoma, who were not eligible for treatment with cisplatin. Progression-free survival was 12.3 months, and overall survival at 1 year was 81.6%. Median duration of response has not been reached. The results compare favorably to historical data with gemcitabine and carboplatin chemotherapy.

Why It Matters: While platinum chemotherapy is the standard treatment for patients with metastatic urothelial carcinoma, some patients are not eligible for treatment with cisplatin. Gemcitabine/carboplatin is poorly tolerated, and survival and durability of response are limited. Enfortumab vedotin is an antibody-drug conjugate that delivers a compound (MMAE), which disrupts the formation and function of microtubules, to certain cells that are highly expressed in urothelial carcinoma. The results show that enfortumab vedotin plus pembrolizumab not only has a high rate of objective responses, but these responses appear to be durable.

Lead Author: Jonathan E. Rosenberg, MD

Read the full abstract (#441)

Presentation Information:
Rapid Abstract Session B: Urothelial Carcinoma; Penile, Urethral, Testicular, and Adrenal Cancers
Friday, February 14, 2020: 7:15 a.m. -7:20 a.m. PT
The Moscone West Building, Level 3, Ballroom

Targeting an Essential Transcription Factor in RCC Demonstrates Effectiveness in Early Studies as Treatment for Clear-Cell Renal Cell Carcinoma

Study Details: Fifty-five patients with advanced clear-cell renal cell carcinoma (RCC), who had received at least one prior therapy (and on average three), were enrolled in an expansion cohort of the first-in-human phase I/II study of the novel drug MK-6482 against advanced solid tumors. Patients received 120 mg of MK-6482 orally once daily. Safety was the primary endpoint.

Key Findings: The most common all-grade, all-cause adverse events were anemia (75%), fatigue (67%), dyspnea (47%), nausea (33%), and cough (31%). Anemia (26%) and hypoxia (15%) were the most common grade-3 adverse events with a median follow up of 13 months. No grade 4/5 drug-related adverse events were observed and only 4% of patients discontinued therapy due to side effects. The overall response rate was 24%; 13 patients were confirmed to have partial responses. Thirty-one patients (56%) had stable disease for a disease control rate of 80%. Over two-thirds of patients with baseline and post-baseline assessments had tumor shrinkage.

Why It Matters: Hypoxia-inducible factor (HIF)-2 α, an important protein in the development and maintenance of RCC, is an attractive therapeutic target. MK-6482 is a first-in-class small molecule that helps to block RCC tumor growth. This drug could potentially be combined with other therapies to provide an alternative approach to treating RCC, particularly given that most side effects form single agent MK-6482 were minor. A Phase 3 pivotal study is planned.

Lead Author: Toni K. Choueiri, MD

Read the full abstract (#611)

Presentation Information:
Oral Abstract Session C: Renal Cell Cancer
Saturday, February 15, 2020: 8:00 a.m. - 8:10 a.m. PT
The Moscone West Building, Level 3, Ballroom

PARP Inhibitor Talazoparib's Additional Mechanism of Action Works Against Prostate Cancer Cells While Sparing Normal Cells

Study Details: Eighty-one patients with metastatic castration-resistant prostate cancer and DNA damage repair mutations received oral talazoparib 1 mg/day as of June 5, 2019. Patients were assessed until radiographic progression, unacceptable toxicity, or consent withdrawal. Primary endpoint is objective response rate (ORR; blinded independent review). A planned interim analysis of safety and efficacy was performed after 20 patients with BRCA1/2 mutations who received treatment for at least 8 weeks. Forty-three patients enrolled by February 12, 2019 were evaluable for the primary endpoint of objective response rate.

Key Findings: The overall objective response rate was 25.6% (13.5-41.2). The objective response rates for patients with BRCA1/2 mutations was 50.0%, and 7.1% for ATM mutations. The median progression-free survival based on radiographic findings was 5.6 months overall and 8.2 months for patients with BRCA1/2 mutations and 3.5 months for those with ATM mutations. The most common treatment-emergent adverse events were anemia, nausea, asthenia, decreased appetite, constipation, and decreased platelet count.

Why It Matters: Talazoparib is a poly ADP ribose polymerase, or PARP, inhibitor. These drugs work by stopping prostate cancer cells from repairing faulty DNA. Talazoparib is unique in that it also traps PARP on DNA, interfering with cancer cell replication. This novel treatment works against prostate cancer cells, while selectively sparing normal cells in metastatic castration-resistant prostate cancer. In addition, the treatment does not have the side effects of chemotherapy or castration treatment. Talazoparib could have a major impact on the treatment of this type of prostate cancer.

Lead Author: Johann S. De Bono, FRCP, MB, MD, PhD

Read the full abstract (#119)

Presentation Information:
Poster Session A: Prostate Cancer
Thursday, February 13, 2020:  
11:30 a.m. - 1:00 p.m. PT
5:30 p.m. - 6:30 p.m. PT
The Moscone West Building, Level 1, West Hall

For more on the latest research in GU cancers, listen to this podcast where members of the Cancer.Net Editorial Board share their expert opinions about three ongoing clinical trials that will be presented at the Symposium.

2020 Genitourinary Cancers Symposium News Planning Team
Neeraj Agarwal, MD, American Society of Clinical Oncology; Robert Dreicer, MD, MS, MACP, FASCO, American Society of Clinical Oncology; Daniel A. Hamstra, MD, American Society for Radiation Oncology; Sumanta K. Pal, MD, American Society of Clinical Oncology.    

View the disclosures for the News Planning Team.

About the Symposium Co-Sponsors
 
ATTRIBUTION TO THE 2020 GENITOURINARY CANCERS SYMPOSIUM IS REQUESTED IN ALL NEWS COVERAGE.