Walter M. Stadler, MD, Fred C. Buffett Professor of Medicine, deputy director of the Comprehensive Cancer Center, the dean for Clinical Research, the University of Chicago (UChicago) Medicine, discusses his role within the Stand Up To Cancer® (SU2C) 4-team initiative, where he will aim to enhance diversity in early-phase clinical trials in underserved urban community.

Martin Edelman, MD, and Linda Fleisher, PhD, of the Fox Chase Cancer Center

Anthony B. El-Khoueiry, MD, and Chanita Hughes-Halbert, PhD, of the University of Southern California (USC) Norris Comprehensive Cancer Center

David Gerber, MD, and Chika Nwachukwu, MD, PhD, of the University of Texas (UT) Southwestern Medical Center

Stadler and Briseis Aschebrook-Kilfoy, PhD, of UChicago Medicine

Each team will focus on initiatives at their respective institutions, which include accelerating and diversifying access to clinical trials at Fox Chase Cancer Center, eliminating enrollment barriers to early-phase trials in diverse populations at USC Norris Comprehensive Cancer Center, and transferring care to enhance access to early-phase cancer clinical trials at UT Southwestern Medical Center.

In addition to existing physician-oriented barriers to early-phase clinical trials for underrepresented populations, there has also been an ongoing discussion surrounding the patient/community barriers for enrolling in these studies, Stadler begins. These barriers can include health literacy, knowledge of what clinical trials may entail, and distrust in the community of the physicians and medical centers providing the clinical trials and treatment, Stadler emphasizes.

Based on these limitations and barriers to early-phase cancer clinical trials, the SU2C 4-team initiative will aim to address these obstacles by partnering with physicians. These partnerships will help determine if addressing physician-related barriers will be sufficient enough to enhance accrual to these trials, or if it is necessary to further address community- and patient-oriented issues, Stadler concludes.

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Walter M. Stadler, MD, discusses his role within the Stand Up To Cancer® 4-team initiative, where he will aim to enhance diversity in early-phase clinical trials in underserved urban community.

Dr Stadler on Enhancing Diversity in Early Phase Clinical Trials For Underserved Communities

Walter M. Stadler, MD, Fred C. Buffett Professor of Medicine and Surgery, dean for clinical research, director of the Genitourinary Oncology Program, and deputy director of the Comprehensive Cancer Center, at the University of Chicago Medicine, discusses the use of active surveillance in prostate cancer.

Active surveillance plays an important role in prostate cancer, specifically in patients who are diagnosed with low-grade localized prostate cancer, says Stadler. Many of those patients are able to live their lives without experiencing any impact from the disease. Active surveillance is an appropriate management strategy in this setting, he adds.

Active surveillance can also be useful to patients who may have received local therapy and then experience biochemical progression of their disease with slow doubling times of their PET prostate-specific antigen, says Stadler; these are doubling times on the order of 2 years or more. Many of those patients, especially if they're elderly or have comorbidities, may not require any intervention. As such, active surveillance may also be appropriate in these patients.

Dr. Stadler on Active Surveillance in Prostate Cancer

Walter M. Stadler, MD, Fred C. Buffett Professor of Medicine and Surgery, chief of the Section of Hematology/Oncology, and director of the Genitourinary Program at the University of Chicago Medicine, discusses the therapeutic landscape of renal cell carcinoma (RCC).

In the last 10 years or so, physicians have relied on VEGFR-targeted therapies in RCC, including pazopanib (Votrient), sunitinib (Sutent), and axitinib (Inlyta). Now, physicians are moving into an era of immunotherapy, which includes nivolumab (Opdivo), pembrolizumab (Keytruda), ipilimumab (Yervoy), and avelumab (Bavencio), enabling researchers to look at combination approaches.

Part of the rationale of exploring combinations of VEGF and immunotherapy agents is their accessibility, says Stadler. However, there is a scientific rationale for their use in combination as well. For example, some of the VEGF pathways have been shown to be immunosuppressive and may induce immunosuppressive properties, says Stadler. Some of the combinations that have been shown to be effective to date include axitinib and avelumab, axitinib and pembrolizumab, and atezolizumab and bevacizumab (Avastin).

Dr. Stadler on the Therapeutic Landscape of RCC

Walter M. Stadler, MD, Fred C. Buffett Professor of Medicine and Surgery, chief of the Section of Hematology/Oncology, and director of the Genitourinary Program at the University of Chicago Medicine, discusses approved and investigational therapies in renal cell carcinoma (RCC).

To date, physicians have access to the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) for patients with poor- and intermediate-risk RCC. In the CheckMate-214 trial, the combination outperformed single-agent sunitinib (Sutent) in patients with metastatic RCC.

There are a number of other combinations that are being examined, adds Stadler, including PD-1 inhibitors combined with various VEGFR inhibitors. Most of the data with combinations are still pending, but in September, positive results were reported with the combination of avelumab (Bavencio) and axitinib (Inlyta). The combination was reported to show a significant improvement in progression-free survival compared with sunitinib in treatment-naïve patients with advanced RCC regardless of PD-L1 expression.

Dr. Stadler on Approved and Investigational Therapies in RCC

Walter M. Stadler, MD, Fred C. Buffett Professor of Medicine and Surgery, chief of the Section of Hematology/Oncology, and director of the Genitourinary Program at the University of Chicago Medicine, discusses sequencing therapies in prostate cancer.

Prostate cancer is becoming quite complicated in terms of sequencing therapy, notes Stadler. The main question that often surfaces is regarding patients who have early castration-resistant prostate cancer (CRPC), and those who have disease progression after standard androgen ablation. In that setting, physicians are beginning to see the entrance of sipuleucel-T (Provenge). Physicians also have access to second-line androgen receptor targeted therapies, hormone therapies, and chemotherapies. Other targeted therapies for specific subsets such as PARP inhibitors in patients with DNA repair mutations are emerging, adds Stadler.

It is not always clear what to use first, explains Stadler, though there is a tendency to use second-line hormonal therapies in early CRPC. Another emerging marker is the androgen receptor splice variant AR-V7, which may help guide treatment choices in the future.

Walter M. Stadler, MD

Articles

Dr Stadler on Enhancing Diversity in Early Phase Clinical Trials For Underserved Communities

Dr. Stadler on Active Surveillance in Prostate Cancer

Dr. Stadler on the Therapeutic Landscape of RCC

Dr. Stadler on Approved and Investigational Therapies in RCC

Dr. Stadler on Sequencing Therapies in Prostate Cancer