Before 2005, systemic treatment of metastatic renal cell carcinoma (RCC) was limited to a few minimally effective options. Since then, new agents have emerged targeting the vascular endothelial growth factor and mTOR pathways, which has improved outcomes for patients. Options increased even further beginning in 2015 with 3 new agents, including the addition of nivolumab, the first immune checkpoint inhibitor to demonstrate improved survival in RCC. RCC has long been considered a malignancy with immunogenic potential, and nivolumab offers the potential for durable responses in some patients with a generally tolerable toxicity profile. With so many drugs available to clinicians and patients, properly integrating immune checkpoint blockade (ICB) into the treatment paradigm is challenging. Additionally, emerging research with other ICB agents, as well as ongoing trials of combination strategies, is likely to further impact clinical decision-making. This article attempts to provide some context to inform systemic treatment decisions in the current landscape, with a particular emphasis on the role of immunotherapy, outlines the ongoing immunotherapy research in RCC, and discusses how treatment may evolve.
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Integrating Immunotherapy Into the Management of Renal Cell Carcinoma
Matthew Zibelman and Elizabeth R. Plimack
Selecting Targeted Therapies for Patients With Renal Cell Carcinoma
Elizabeth R. Plimack and Gary R. Hudes
Advanced renal cell carcinoma (RCC) is a heterogeneous disease with variable histology, biology, and response to treatment. In the past 5 years, 6 new agents have been approved for the treatment of RCC, and many more are in clinical development. With an ever-increasing number of treatment options, selecting among them for a particular patient can be a daunting task for clinicians. This article describes how treatment choice can be guided by the disease setting and histology, as well as patient characteristics, comorbidities, and preference within the context of available data. Results from clinical trials are combined with practical considerations to make recommendations for first-line and subsequent treatment of patients with clear cell and non-clear cell RCC. These recommendations should supplement the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for the treatment of advanced RCC.
Integration of Immunotherapy Into the Treatment of Advanced Urothelial Carcinoma
Pooja Ghatalia and Elizabeth R. Plimack
Five new PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of metastatic urothelial carcinoma (UC): pembrolizumab, atezolizumab, durvalumab, nivolumab, and avelumab. Although cisplatin-based chemotherapy remains the recommended frontline option for cisplatin-eligible patients with metastatic UC, immunotherapy is now an available option in the second-line setting as well as the frontline setting for selected cisplatin-ineligible patients who are either unable to tolerate chemotherapy or PD-L1–positive. This review describes the updated clinical efficacy of these checkpoint inhibitors in the treatment of advanced UC and suggests how they can be sequenced in the context of available chemotherapeutic options.
Optimizing Systemic Therapy for Bladder Cancer
Sumanta K. Pal, Matthew I. Milowsky, and Elizabeth R. Plimack
Over the past several decades, few new systemic agents have been incorporated into the treatment paradigm for bladder cancer. Platinum-based therapy remains the cornerstone of treatment in the perioperative and metastatic settings. Despite level one evidence, use of cisplatin-based therapy in the neoadjuvant setting has been dismal. Second-line therapy for metastatic disease has only modest activity with no survival benefit. However, the elucidation and investigation of novel molecular targets, new therapeutics, and associated biomarkers with strong biologic rationale are actively changing the landscape in bladder cancer. Although the field is moving rapidly, no new drug approvals are currently pending and a need remains to continue to educate the medical oncology and urology communities on the optimal use of currently available treatments. This article outlines the evidence, including that from prospective studies and meta-analyses, providing the basis for the current recommendations from NCCN, and details previous and ongoing studies of targeted therapy for bladder cancer.
Distress and Financial Distress in Adults With Cancer: An Age-Based Analysis
Caitlin R. Meeker, Yu-Ning Wong, Brian L. Egleston, Michael J. Hall, Elizabeth R. Plimack, Lainie P. Martin, Margaret von Mehren, Bianca R. Lewis, and Daniel M. Geynisman
Background: Although financial distress is commonly recognized in patients with cancer, it may be more prevalent in younger adults. This study sought to evaluate disparities in overall and financial distress in patients with cancer as a function of age. Methods: This was a single-center cross-sectional study of patients with solid malignancies requiring cancer therapy. The patient questionnaire included demographics, financial concerns, and measures of overall and financial distress. Data analyses compared patients in 3 age groups: young (<50 years), middle-aged (50–64 years), and elderly (≥65 years). Results: The cohort included 119 patients (median age, 62 years; 52% female; 84% white; 100% insured; 36% income ≥$75,000). Significant financial concerns included paying rent/mortgage (P=.003) and buying food (P=.032). Impact of Event Scale (IES) results revealed significant distress in 73% young, 64% middle-aged, and 44% elderly patients. The mean Distress Thermometer (DT) score was 6.1 (standard deviation [SD], 2.9) for young patients, 5.4 (SD, 2.6) for middle-aged, and 4.4 (SD, 3.3) for elderly patients. Young patients were more likely than elderly patients to have a higher IES distress score (P=.016) and DT score (P=.048). The mean InCharge score was lowest (indicating greatest financial distress) in the young group and progressed with age: 5.0 (SD, 1.9), 5.7 (SD, 2.7), and 7.4 (SD, 1.9), respectively (P<.001). Multivariable analyses revealed that the relationship between financial distress and overall distress was strongest in the middle-age group; as the DT increased by 1 point, the InCharge scores decreased by 0.52 (P<.001). Conclusions: Overall and financial distress are more common in young and middle-aged patients with cancer. There are several factors, including employment, insurance, access to paid sick leave, children, and education, that affect younger and middle-aged adults and are less of a potential stressor for elderly individuals.
Follow-Up Management of Patients With Testicular Cancer: A Multidisciplinary Consensus-Based Approach
Clair J. Beard, Shilpa Gupta, Robert J. Motzer, Elizabeth K. O'Donnell, Elizabeth R. Plimack, Kim A. Margolin, Charles J. Ryan, Joel Sheinfeld, and Darren R. Feldman
Testicular cancer is the most common cancer in men aged 15 to 40 years in the United States, Canada, and many European countries. Given the excellent prognosis of most men with testicular cancer, updates in care after treatment have become very important. This article provides a review of the available evidence, integrated with expert medical judgment, in the area of testicular cancer follow-up.
Prostate Cancer
James Mohler, Robert R. Bahnson, Barry Boston, J. Erik Busby, Anthony D'Amico, James A. Eastham, Charles A. Enke, Daniel George, Eric Mark Horwitz, Robert P. Huben, Philip Kantoff, Mark Kawachi, Michael Kuettel, Paul H. Lange, Gary MacVicar, Elizabeth R. Plimack, Julio M. Pow-Sang, Mack Roach III, Eric Rohren, Bruce J. Roth, Dennis C. Shrieve, Matthew R. Smith, Sandy Srinivas, Przemyslaw Twardowski, and Patrick C. Walsh
Kidney Cancer, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology
Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Sam Bhayani, William P. Bro, Sam S. Chang, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Mayer Fishman, Thomas H. Gallagher, John L. Gore, Steven L. Hancock, Michael R. Harrison, Won Kim, Christos Kyriakopoulos, Chad LaGrange, Elaine T. Lam, Clayton Lau, M. Dror Michaelson, Thomas Olencki, Phillip M. Pierorazio, Elizabeth R. Plimack, Bruce G. Redman, Brian Shuch, Brad Somer, Guru Sonpavde, Jeffrey Sosman, Mary Dwyer, and Rashmi Kumar
The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non–clear cell renal carcinoma. These guidelines are developed by a multidisciplinary panel of leading experts from NCCN Member Institutions consisting of medical oncologists, hematologists and hematologic oncologists, radiation oncologists, urologists, and pathologists. The NCCN Guidelines are in continuous evolution and are updated annually or sometimes more often, if new high-quality clinical data become available in the interim.
Prostate Cancer, Version 3.2012 Featured Updates to the NCCN Guidelines
James L. Mohler, Andrew J. Armstrong, Robert R. Bahnson, Barry Boston, J. Erik Busby, Anthony Victor D’Amico, James A. Eastham, Charles A. Enke, Thomas Farrington, Celestia S. Higano, Eric Mark Horwitz, Philip W. Kantoff, Mark H. Kawachi, Michael Kuettel, Richard J. Lee, Gary R. MacVicar, Arnold W. Malcolm, David Miller, Elizabeth R. Plimack, Julio M. Pow-Sang, Mack Roach III, Eric Rohren, Stan Rosenfeld, Sandy Srinivas, Seth A. Strope, Jonathan Tward, Przemyslaw Twardowski, Patrick C. Walsh, Maria Ho, and Dorothy A. Shead
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer provide multidisciplinary recommendations for the clinical management of patients with prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Abiraterone acetate is a first-in-class hormonal agent that represents a new standard of care for patients with metastatic castration-recurrent prostate cancer who have previously received docetaxel (category 1 recommendation). Abiraterone acetate also received category 2B recommendations in the prechemotherapy setting for asymptomatic patients or symptomatic patients who are not candidates for docetaxel. The NCCN Prostate Cancer Panel also added new indications for existing agents, including the option of sipuleucel-T as second-line therapy. In addition, brachytherapy in combination with external beam radiation therapy with or without androgen deprivation therapy is now an alternative for patients with high-risk localized tumors or locally advanced disease.
Prostate Cancer, Version 1.2014
James L. Mohler, Philip W. Kantoff, Andrew J. Armstrong, Robert R. Bahnson, Michael Cohen, Anthony Victor D’Amico, James A. Eastham, Charles A. Enke, Thomas A. Farrington, Celestia S. Higano, Eric Mark Horwitz, Mark H. Kawachi, Michael Kuettel, Richard J. Lee, Gary R. MacVicar, Arnold W. Malcolm, David Miller, Elizabeth R. Plimack, Julio M. Pow-Sang, Sylvia Richey, Mack Roach III, Eric Rohren, Stan Rosenfeld, Eric J. Small, Sandy Srinivas, Cy Stein, Seth A. Strope, Jonathan Tward, Patrick C. Walsh, Dorothy A. Shead, and Maria Ho
The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer. This report highlights notable recent updates. Radium-223 dichloride is a first-in-class radiopharmaceutical that recently received approval for the treatment of patients with symptomatic bone metastases and no known visceral disease. It received a category 1 recommendation as both a first-line and second-line option. The NCCN Prostate Cancer Panel also revised recommendations on the choice of intermittent or continuous androgen deprivation therapy based on recent phase III clinical data comparing the 2 strategies in the nonmetastatic and metastatic settings.