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This activity is supported by an educational grant from Merck Sharp & Dohme Corp.
Community Practice Connections™: Immunotherapeutic Strategies with the Potential to Transform Treatment for Genitourinary Cancers
Release Date: August 29, 2018
Expiration Date: August 29, 2019
Media: Internet - based
Unmet clinical needs remain in the management of genitourinary (GU) cancers, particularly for your patients with advanced forms of these tumors. As the field of immunotherapies rapidly advances, you face challenges in ensuring the provision of cutting-edge care to manage these most difficult-to-treat forms of cancer. In this online activity, focused on expert interviews and clinical vignettes, you will engage with renowned medical experts in the treatment of patients with renal cell carcinoma (RCC), bladder cancer, prostate cancer, and less common but important malignancies, such as testicular and penile cancers. Charles G. Drake, MD, PhD, Joaquim Bellmunt, MD, PhD, Douglas G. McNeel, MD, PhD, and Brian I. Rini, MD, FACP, will provide insight into staging and sequencing options. You will learn how the latest evidence on immunotherapies can be contextualized, given rapidly changing treatment paradigms to manage these challenging GU tumors. The content and interviews are based on presentations delivered in June 2018 at the Immunotherapeutic Strategies with the Potential to Transform Treatment for GU Cancers satellite symposium held adjunct to the 2018 American Society of Clinical Oncology Annual Meeting.
Acknowledgment of Commercial SupportThis activity is supported by an educational grant from Merck Sharp & Dohme Corp.
Instructions for This Activity and Receiving Credit
This educational activity is directed toward medical oncologists interested in the treatment of GU cancers. Nurse practitioners, physician assistants, nurses, and other healthcare professionals involved in the treatment and management of patients with GU cancers are also invited to participate.
At the conclusion of this activity, participants should be better prepared to:
- Outline the use of patient- and disease-specific characteristics to inform clinical decision-making in the management of patients with GU malignancies
- Discuss current strategies and practice-changing evidence for the management of patients with GU malignancies across multiple lines of care
- Explain how to proactively mitigate expected treatment-related toxicities associated with immunotherapeutic and targeted approaches to treating GU cancers
- Apply emerging clinical trial data for the management of GU malignancies in the context of changing treatment paradigms in the field
Faculty, Staff, and Planners' Disclosure
Professor of Oncology and Immunology
Director, Genitourinary Cancer Program
Co-director of the Immunotherapy Program
Herbert Irving Comprehensive Cancer Center
Columbia University Medical Center
New York, NY
Disclosure: Grant/Research Support: Aduro Biotech, Bristol Myers Squibb, Janssen; Consultant: Agenus, Dendreon, NexImmune, ImmunExcite, Janssen, Lilly, Merck, Pierre Fabre, Roche/Genentech; Patents: AZ, Medimmune, BMS, Janssen; Ownership Interests: Compugen, Harpoon, Kleo, Potenza, Tizona
Director, Bladder Cancer Center
Dana-Farber Cancer Institute
Associate Professor of Medicine, Harvard Medical School
Disclosure: Grant/Research Support: Sanofi Aventis, Novartis, Takeda, Pfizer; Consultant: Genentech, MSD, Pfizer, GSK, BMS, Pierre-Fabre, Sanofi Aventis, Astellas, OncoGenex, Janssen
Professor of Medicine
University of Wisconsin-Madison
Disclosure: : Grant/Research Support: Madison Vaccines, Inc.; Consultant: Madison Vaccines, Inc; Clinical Trial Research Support: Novartis, BMS, Merck & Co., Janssen
Professor of Medicine, Lerner College of Medicine
Leader, GU Program
Department of Hematology and Oncology
Cleveland Clinic Taussig Cancer Institute
Disclosure: Grant/Research Support: Pfizer, Merck, Genentech; Consultant: Merck, Pfizer
The staff of Physicians' Education Resource®, LLC have no relevant financial relationships with commercial interests to disclose.
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Off-Label Disclosure and Disclaimer
This CMEactivity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CMEactivity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician or nurse relative to diagnostic, treatment, or management options for a specific patient’s medical condition. The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER®.
PER Pulse Recap™PER Pulse Recap (1 of 3)
Engage with renowned medical experts in the treatment of genitourinary (GU) cancers, Charles G. Drake, MD, PhD, Joaquim Bellmunt, MD, PhD, Douglas G. McNeel, MD, PhD, and Brian I. Rini, MD, FACP, in the online continuing medical education (CME) activity, Community Practice Connections™: Immunotherapeutic Strategies With the Potential to Transform Treatment for Genitourinary Cancers. Through expert interviews and clinical vignettes, you will gain insight into the rationale for checkpoint inhibition (CPI) strategies and explore the emerging role of immunotherapy in the treatment of urologic malignancies. You will learn how the latest evidence in immunotherapies can be contextualized, given rapidly changing treatment paradigms to manage these challenging GU tumors. The content and interviews are based on presentations delivered in June 2018 at the Immunotherapeutic Strategies With the Potential to Transform Treatment for GU Cancers satellite symposium held adjunct to the 2018 American Society of Clinical Oncology Annual Meeting.
This first of 3 PER Pulse™ Recaps will focus on the therapeutic options for patients with advanced or metastatic urothelial cancer (mUC) in the first line and subsequent lines of therapy.
Cisplatin-based chemotherapy is standard first-line treatment for mUC. However, approximately 50% of patients are ineligible for cisplatin due to poor performance status, renal impairment, or other comorbidities. For these cases, carboplatin-based combinations are valid alternative options, although they are associated with inferior survival. Additional new strategies for cisplatin-ineligible patients are therefore urgently needed.
Checkpoint inhibition therapy is associated with significant antitumor activity in mUC, both as an initial therapy in cisplatin-ineligible patients and in patients with cisplatin-pretreated disease. For patients with mUC, however, PD-L1 expression should not be considered a definitive marker of response to treatment with CPIs.
“We have been discussing the five agents that are approved for treating bladder cancer in the second line. We have gone through the long-term follow-up results obtained with atezolizumab, pembrolizumab, and nivolumab. With now 2 years of follow-up, we see patients who have long-term durable responses, and that is good news.”
— Joaquim Bellmunt, MD, PhD
According to the National Comprehensive Cancer Network (NCCN) guidelines,1 CPIs recommended for the treatment of locally advanced or mUC that has progressed during or within 12 months of platinum-based chemotherapy include pembrolizumab (category 1 recommendation) or alternative preferred regimens of atezolizumab, nivolumab, durvalumab, or avelumab.
The NCCN guidelines stratify treatment for patients with mUC based on eligibility for cisplatin therapy.
For patients with mUC who are eligible for cisplatin, NCCN guideline‒preferred regimens are gemcitabine and cisplatin or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) with growth factor support. Both options are category 1 recommendations.
For patients with mUC who are ineligible for cisplatin therapy, NCCN guideline‒preferred first-line systemic treatment options include treatment with atezolizumab, pembrolizumab, or gemcitabine and carboplatin. Atezolizumab is a preferred regimen only in patients whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells covering ≥5% of the tumor area), and pembrolizumab is a preferred regimen only in patients whose tumors express PD-L1 (combined positive score ≥10). Both atezolizumab and pembrolizumab are first-line recommended therapeutic options for patients who are ineligible for platinum-based chemotherapy, regardless of PD-L1 expression.1
1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Bladder Cancer. Version 5.2018. https://www.nccn.org/professionals/physician_gls/PDF/bladder.pdf. Accessed August 8, 2018.
PER Pulse Recap (2 of 3)
As a follow-up to the online continuing medical education (CME) activity, Community Practice Connections™: Immunotherapeutic Strategies With the Potential to Transform Treatment for Genitourinary Cancers, this second of 3 PER Pulse™ Recaps will focus on the recent data in patients with renal cell carcinoma (RCC) treated with CPIs. Below are some highlights from the activity.
Although the current role of CPIs in the treatment of RCC is limited to use of nivolumab in relapsed patients and in the nonsurgically resectable metastatic treatment setting, active investigation with multiple other CPIs in this disease state is ongoing.
“The standard of care is shifting from TKIs [tyrosine kinase inhibitors] like sunitinib and pazopanib to ipilimumab/nivolumab. The data about PD-L1 positivity with ipilimumab/nivolumab, I would summarize as – patients whose tumor cells express PD-L1 are more likely to respond to the regimen. They are more likely to have a complete response, but PD-L1-negative patients still benefit.”
— Brian I. Rini, MD, FACP
In the phase III CheckMate 214 study1 combining nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks dosed 4 times followed by maintenance treatment with nivolumab 3 mg/kg every 2 weeks, 1096 patients were randomized to receive the combination of immunotherapies (n=550) or sunitinib (n=546). After a median follow-up of 25.2 months in intermediate- and poor-risk patients, the 18-month overall survival (OS) rate was 75% (95% CI, 70-78) in the nivolumab-plus-ipilimumab treatment arm and 60% (95% CI, 55-65) in the sunitinib treatment arm. Median OS was not reached with nivolumab plus ipilimumab versus 26.0 months with sunitinib (hazard ratio [HR] for death, 0.63; P <.001).
In the nivolumab-plus-ipilimumab group, treatment-related adverse events (trAEs) were reported in 509/547 patients (93%) and 521/535 patients (97%) in the sunitinib treatment arm. Grade 3/4 AEs were less common in the nivolumab-plus-ipilimumab group versus the sunitinib group, occurring in 250 patients (46%) and 335 patients (63%), respectively.
In the phase III IMmotion151 study2 of atezolizumab in combination with bevacizumab, use of atezolizumab and bevacizumab in combination versus sunitinib reduced the risk of progression or death by 26% (HR, 0.74; 95% CI, 0.57-0.96; P =.0217). Over 15 months of follow-up, the median progression-free survival (PFS) with atezolizumab and bevacizumab was 11.2 months (95% CI, 8.9-15.0) versus 7.7 months (95% CI, 6.8-9.7) with sunitinib. The trAEs of grade 3/4 severity were less frequent in patients receiving combination therapy (41%) versus patients receiving sunitinib (54%).
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378:1277-1290. doi: 10.1056/NEJMoa1712126.
- Motzer RJ, Powles T, Atkins MB, et al. IMmotion151: a randomized phase III study of atezolizumab plus bevacizumab vs sunitinib in untreated metastatic renal cell carcinoma (mRCC). J Clin Oncol. 2018;36(suppl 6S; abstr 578).
PER Pulse Recap (3 of 3)
This third of 3 PER Pulse™ Recaps will focus on the strategies for mitigating toxicities associated with treatment with checkpoint inhibitors (CPIs). Below are some highlights from the activity.
According to the ASCO Clinical Practice Guidelines for the management of immune-related adverse events (irAEs), education should be provided to both the patient and their family caregivers regarding immunotherapies, their mechanism of action, and possible irAEs before therapy is initiated, throughout treatment, and continuing into the survivorship phase of care.1
Recognition of irAEs related to the skin may be straightforward, but recognition in other organ systems can be more nuanced.
“The first key in treating these adverse events is recognizing them. Pneumonitis often presents as a new dry cough, sometimes as shortness of breath, or sometimes as hypoxia tested on a pulse ox. Recognizing that early is important, because if you treat these adverse events earlier, they tend to resolve more quickly and be more readily treatable.”
— Charles G. Drake, MD, PhD
The irAEs can affect virtually any organ system, including the skin, gastrointestinal (GI) tract, lungs, endocrine, thyroid, adrenal, pituitary, musculoskeletal, renal, nervous, hematologic, cardiovascular, and ocular systems. Changes in any of these systems post-therapy should confer a high level of suspicion that the changes may be treatment-related.1
Commonly, irAEs present as mild to moderate in severity and respond well to treatment. In some cases, serious irAEs can occur, including severe colitis, toxic epidermal necrolysis, myocarditis, pneumonitis, encephalitis, and autoimmune type I diabetes mellitus presenting as diabetic ketoacidosis.2 Early recognition and early treatment are proactive strategies to help to resolve irAEs.
- Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018;36:1714-1768. doi: 10.1200/JCO.2017.77.6385.
- Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5:95. doi: 10.1186/s40425-017-0300-z.
For additional commentary about these topics and others, visit www.gotoper.com to access more resources from the activity, Community Practice Connections™: Immunotherapeutic Strategies With the Potential to Transform Treatment for Genitourinary Cancers.
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