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Physicians' Education Resource®, LLC, designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
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Acknowledgement of Commercial Support
This activity is supported by educational grants from Regeneron Pharmaceuticals, Inc. and Sanofi Genzyme.
Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of Immunotherapy
Release Date: August 13, 2018
Expiration Date: August 13, 2019
Media: Internet - based
For busy oncologists focused on the management of complex patients with advanced or metastatic cSCC, this activity provides you with an up-to-date perspective on the efficacy and safety evidence underpinning the use of immunotherapy for this patient population.
Below are some clinical pearls and highlights from the activity:
- Risk factors for the development of cSCC include cumulative sun exposure and immunosuppression status. Immunotherapy holds promise of therapeutic benefit for most patients; however, further research is needed to determine appropriate therapies for patients who are immunosuppressed.
- Emerging evidence shows that immunotherapy treatment for patients with cSCC is associated with objective response rates between 40% and 50%, along with tolerable safety profiles. Expected US Food and Drug Administration approval is eagerly awaited by oncologists.
- Treatment with immune checkpoint inhibitors provides survival benefits, but associated toxicities need to be carefully managed. Upfront educational efforts with both patients and family caregivers may encourage prompt and effective management of immune-related adverse events.
“It is difficult to overstate the need for novel strategies in treating cutaneous squamous cell carcinoma. The current standard of care includes disfiguring surgical resections, repeated radiation, or highly toxic chemotherapy. The promise of immunotherapy both to potentially shrink tumors and to control advanced unresectable disease over indefinite periods of time is extremely exciting for patients. ”
‒ Jason J. Luke, MD
The University of Chicago
Acknowledgement of Commercial SupportThis activity is supported by educational grants from Regeneron Pharmaceuticals, Inc. and Sanofi Genzyme.
Instructions for This Activity and Receiving Credit
This educational activity is directed toward medical oncologists. Nurse practitioners, nurses, physician assistants, pharmacists, researchers, and other healthcare professionals interested in the treatment of cSCC are also invited to participate, as well as those involved in the multidisciplinary care of patients with cSCC, including dermatologists, surgeons, head and neck cancer surgeons, and Mohs surgeons.
At the conclusion of this activity, you should be better prepared to:
- Discuss current unmet clinical needs in the management of advanced/metastatic cSCC and evidence-based recommendations for the care of patients with these tumors
- Determine the rationale for development of cytoreductive strategies for the management of patients with advanced/metastatic cSCC
- Report recent evidence concerning the use of emerging immunotherapeutic approaches for the treatment of patients with advanced or metastatic cSCC
- Describe multidisciplinary approaches to plan for and proactively mitigate the impact of immune-related adverse events in patients who are undergoing treatment for advanced/metastatic cSCC
Chief, Translational Research & Immuno-Oncology
Director, Cutaneous Malignancies
The Angeles Clinic and Research Institute
Director, Experimental Therapeutics
Cedars-Sinai Medical Care Foundation
Los Angeles, CA
Disclosure: Consultant: Amgen, Novartis, Roche, BMS, Merck; Speakers’ Bureau: BMS, Genentech, Novartis, Amgen; Contracted Research for Institution: AstraZeneca, BMS, Celldex, Genentech, Immunocore, Incyte, Merck, Merck-Serono, MedImmune, Novartis, Pfizer, Rinat, Roche
Assistant Professor of Medicine
The University of Chicago Medicine
Disclosure: Grant/Research Support: AbbVie, Array, Boston Biomedical, Bristol-Myers Squibb, Celldex, CheckMate, Corvus, Delcath, Five Prime, Genentech, lmmunocore, lncyte, Medlmmune, Macrogenics, Novartis, Pharmacyclics, Palleon, Merck, Tesaro, Xencor; Consultant: 7 Hills, Actym, Amgen, Array, AstraZeneca, BeneVir, Bristol-Myers Squibb, Castle, Check-Mate, Compugen, EMO Serono, Gilead, Janssen, Merck, NewLink, Nimbus, Novartis, Palleon, RefleXion, Syndax, Tempest, WntRx; Travel: Amgen, Array, AstraZeneca, BeneVir, Bristol-Myers Squibb, Castle, CheckMate, EMD Serono, Gilead, Janssen, Merck, NewLink, Novartis, RefleXion
Vice Chair, Department of Cutaneous Oncology
Moffitt Cancer Center
Disclosure: Research Funding (Institute): BMS, Merck, Amgen, GSK, Novartis, Regeneron, HUYA; Advisory Board: Castle Biosciences, BMS, EMD Serono, Genentech, Regeneron; Data Safety Monitoring Board: AstraZeneca
Associate Professor of Dermatology
Harvard Medical School
Director, Dermatologic Surgery Center
Brigham and Women’s Hospital
Disclosure: Grant/Research Support: Site PI, Regeneron EMPOWER-CSCC Trial
The staff of Physicians' Education Resource®, LLC have no relevant financial relationships with commercial interests to disclose.
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As a sponsor accredited by the ACCME, it is the policy of Physicians’ Education Resource®, LLC, (PER®) to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines relevant financial relationships as financial relationships in any amount occurring within the past 12 months that creates a conflict of interest (COI).
Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.
Off-Label Disclosure and Disclaimer
This CME/CE activity 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 CME/CE activity 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)
Join renowned medical experts in the treatment of cutaneous squamous cell carcinoma (cSCC), Omid Hamid, MD, Jason J. Luke, MD, Nikhil I. Khushalani, MD, and Chrysalyne Schmults, MD, MSCE, in the online continuing medical education (CME) activity, New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of Immunotherapy. You will engage with the faculty through expert interviews and clinical vignettes to gain insight into staging and sequencing options; consider how emerging immunotherapy options will impact the treatment paradigm; investigate best practices for management of associated toxicities; and explore the role of genomic testing and biomarkers in cSCC.
This first of 3 PER Pulse™ Recaps will focus on evidence supporting the use of immunotherapy in patients with advanced or metastatic cSCC.
Dr. Hamid characterized the potentially practice-changing implications for the management of patients with cSCC:
“Immunotherapy for cutaneous squamous cell carcinoma is here to stay. We look forward to the FDA ruling on cemiplimab and also the advent of the use of pembrolizumab for these patients.”
— Omid Hamid, MD
The use of immunotherapy for the treatment of cSCC is an active area of research with emerging recent evidence to improve outcomes for patients with locally advanced or metastatic cSCC. Several phase II trials of immune checkpoint inhibitors (ICPis) in cSCC are ongoing (Table 1), with some phase II data published.
Efficacy results from phase I expansion cohorts of patients with locally advanced or metastatic cSCC and a phase II cohort of patients with metastatic disease treated with cemiplimab showed an objective response rate (ORR) of 47% in the metastatic cohort (Table 2).1 Cemiplimab was well tolerated, with no new safety signals reported. The most common adverse events (AEs) in the phase II study were diarrhea (27%), fatigue (24%), nausea (17%), constipation (15%), and rash (15%).
A small phase II trial of pembrolizumab in 10 patients with metastatic cSCC showed clinical activity with an ORR of 40%, with complete response (CR) in 1 patient (10%); partial response (PR) in 3 patients (30%); and stable disease (SD) in 1 patient (10%). All patients with CR, PR, and SD have not progressed at the current follow-up. Two grade 3 AEs were reported: hepatitis and pneumonitis.2
- Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med. 2018;379:341-351. doi: 10.1056/NEJMoa1805131.
- Kudchadkar RR, Yushak ML, Lawson DH, et al. Phase II trial of pembrolizumab (MK-3475) in metastatic cutaneous squamous cell carcinoma (cSCC). J Clin Oncol. 2018;36(suppl; abstr 9543).
PER Pulse Recap (2 of 3)
Insight from Nikhil I. Khushalani, MD – PER Pulse™ Recap:
New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of Immunotherapy
As a follow-up to the online continuing medical education (CME) activity, New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of Immunotherapy, this second of 3 PER Pulse™ Recaps will focus on the role of tumor mutational burden (TMB) as a potential biomarker in cutaneous squamous cell carcinoma (cSCC). Below are some highlights from the activity.
An emerging biomarker of response to anti–PD-1 therapy is TMB. Tumor mutational burden is defined as the total number of mutations per coding region of a tumor genome.1 Increasing tumor mutation load (TML) translates to an increased potential for immune activity (Figure).2
“Low-grade tumors tend to have a lower TMB. This is an important factor in helping us determine, as a biomarker, who potentially may respond to immunotherapy. The possible hypothesis for that is the increase in neoantigens, which in turn may serve as targets for recognition by the immune system.”
— Nikhil I. Khushalani, MD
Aggressive forms of cSCC are characterized by a very high TML. Although there is a substantial biological rationale supporting the use of immune checkpoint inhibitors, such as anti–PD-1 antibodies, in patients with advanced cSCC, the encouraging preliminary findings will need confirmation through larger clinical trials.3
- Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 2017;377:2500-2501. doi: 10.1056/NEJMc1713444.
- Khushalani NI. Unpublished data. June 2018.
- Ribero S, Stucci LS, Daniels, GA, et al. Drug therapy of advanced cutaneous squamous cell carcinoma: is there any evidence? Curr Opin Oncol. 2017;29:129-135. doi: 10.1097/CCO.0000000000000359.
PER Pulse Recap (3 of 3)
Insight from Jason J. Luke, MD, FACP – PER Pulse™ Recap:
New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of Immunotherapy
As a follow-up to the online continuing medical education (CME) activity, New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of Immunotherapy, this third of 3 PER Pulse™ Recaps will focus on best practices for management of toxicities associated with immunotherapy. Below are some highlights from the activity.
Immune checkpoint inhibitors provide durable clinical benefit to some patients, but their use is often associated with a range of adverse events (AEs) related to their specific mechanism of action. These immune-related AEs (irAEs) can affect the skin, gastrointestinal 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
The most common irAEs are mild to moderate in severity, but serious and potentially life-threatening irAEs can occur, including severe colitis, toxic epidermal necrolysis, myocarditis, pneumonitis, encephalitis, and autoimmune type I diabetes mellitus presenting as diabetic ketoacidosis. Immunotherapy treatment–related deaths have been reported in up to 2% of patients participating in clinical trials.2
“It’s really quite clear at this point that if we have good communication with patients and their families and we learn about what is happening early on, we can block most of those toxicities from getting much worse. We don’t have great strategies to have patients not get toxicity, but if we can catch it early, we tend to be able to manage it much better.”
— Jason J. Luke, MD, FACP
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