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Patients diagnosed with metastatic basal cell carcinoma (BCC) have a poor prognosis. The current standard of care for adults with locally advanced or metastatic BCC who are not candidates for surgery or radiation therapy is treatment with hedgehog pathway inhibitors (HHIs). For patients who progress while on this therapy, further treatment options are limited. There is also a need for real-world clinical practice data on the clinical characteristics, management, disease progression, and survivorship of these patients. The ongoing CemiplimAb-rwlc Survivorship and Epidemiology (CASE) study is a phase IV, multicenter, prospective, noninterventional survivorship and epidemiology cohort study evaluating the effectiveness and safety of cemiplimab, a fully human immunoglobulin G4 monoclonal antibody that blocks the interaction between the programmed cell death-1 (PD-1) receptor and its ligands. This paper describes one cohort of the CASE study of patients with locally advanced or metastatic BCC who have failed or are intolerant of HHIs or for whom HHI therapy is not appropriate. Outcome measures of the study include response to treatment, quality of life, safety, treatment patterns, patient experience, and survival. This study could provide a more complete characterization of this patient population and fill knowledge gaps related to real-world treatment utilization and patient outcomes. Clinical Trial registration: NCT03836105 [ABSTRACT FROM AUTHOR]

Background: Cemiplimab is the first treatment approved in the United States (as cemiplimab-rwlc) for patients with metastatic basal-cell carcinoma (mBCC) or locally advanced disease (laBCC) after hedgehog inhibitor (HHI) treatment or for whom an HHI is not appropriate. Cemiplimab provided substantial clinical benefit and an acceptable safety profile in patients with laBCC who discontinued HHI therapy due to progressive disease (PD), intolerance, or no better than stable disease (SD) after 9 months (NCT03132636). Objective: Here, we present the primary analysis of the mBCC cohort. Methods: Patients with mBCC (nodal or distant) post- HHI treatment received cemiplimab 350 mg intravenously every 3 weeks for up to 93 weeks or until PD. The primary end point was objective response rate (ORR) by independent central review (ICR). Key secondary end points included safety and tolerability, ORR per investigator (INV) assessment, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and complete response (CR) rate (data cutoff date: May 20, 2021). Results: Fifty-four patients were enrolled (70.4% male; median age 63.5 years [range, 38-90]; Eastern Cooperative Oncology Group performance status 0 [66.7%] and 1 [33.3%]). Median duration of follow-up was 8.4 months (range, 1.5- 36.2). ORR per ICR was 24.1% (95% CI, 13.5-37.6), with 1 CR and 12 partial responses (PRs). ORR per INV was 25.9% (95% CI, 15.0-39.7), with 2 CRs and 12 PRs. Among responders, median time to response per ICR was 4.0 months (range, 2.0-10.5). Estimated median DOR per ICR was 16.7 months (95% CI, 9.8-not evaluable). Disease control rate was 63.0% (95% CI, 48.7-75.7) per ICR and 70.4% (95% CI, 56.4-82.0) per INV. Median OS was not reached. Median PFS per ICR was 8.3 months (95% CI, 4.2-15.9). The most common treatment-related adverse events were fatigue (37.0%), diarrhea (14.8%), pruritus (13.0%), hyperthyroidism (9.3%), and arthralgia (9.3%), as well as hypothyroidism, asthenia, constipation, and maculopapular rash (7.4% each). There were no treatment-related deaths. Conclusions: Until the current study, patients with mBCC who had progressed on or showed intolerance to first-line HHI therapy had no standard second-line options. Cemiplimab provided clinically meaningful antitumor activity, including durable responses, and an acceptable safety profile in this patient population. These results complement those of the laBCC cohort and suggest that patients with mBCC may benefit from treatment with cemiplimab following first-line HHI therapy or for whom HHI therapy is not appropriate. Funding: Regeneron Pharmaceuticals, Inc. and Sanofi. Medical writing and editorial support were provided by Daniel Himmel, PhD, of Prime (Knutsford, UK) funded by Regeneron Pharmaceuticals, Inc. and Sanofi. Previously presented (encore) at the American Association for Cancer Research (AACR) 2022 Annual Meeting, April 8-12, 2022, in New Orleans, LA, USA. [ABSTRACT FROM AUTHOR]

Standard treatment for basal cell carcinoma (BCC) is surgical resection. However, a subset of locally advanced BCCs may be unresectable, or surgery would result in unacceptable functional or cosmetic defects. Outcomes after definitive radiation therapy for locally advanced BCC in the contemporary era are not well established. We sought to determine locoregional control and disease-specific survival after definitive radiation therapy for locally advanced BCC. Patients with locally advanced BCC treated with definitive radiation therapy between 2005 and 2020 from 4 academic tertiary care institutions were included. Locally advanced BCCs were defined as patients with unresectable disease, or locations where margin negative resection would lead to unacceptable cosmetic or functional deficit. Additionally, a set of 5 risk factors (size ≥4 cm, the presence of bone invasion, PNI, immunocompromised patient, and recurrent disease) was separately defined and outcomes were investigated. Six hundred eight locally advanced BCC cases were identified, of which 140 were treated with definitive radiation therapy. Median follow-up was 22.9 months (1.5-207.2 months). One hundred one (72.1%) tumors were treated with upfront definitive radiation therapy, whereas 39 (27.9%) were treated for a recurrence. Five-year Kaplan-Meier estimated locoregional control was 78%. The majority of locoregional failures were local recurrences (95.5%). Larger tumor diameter was a risk factor for locoregional failure (P =.045), whereas recurrent disease was not (P =.29). Cumulative incidence of BCC-related mortality at 5 years was 9.5%. Patients with 0 risk factors had a 5-year FF-LRF of 92.4%, whereas those with 1+ risk factors had a 5-year freedom from locoregional failure of 68.5% (P =.004). Definitive radiation therapy for locally advanced BCC has excellent locoregional control, with tumor size representing the only risk factor for recurrence in this study. [ABSTRACT FROM AUTHOR]

Although the cost of acitretin has beendecreasingsince2013,itisstill4to10timeshigher than in other countries and is a barrier to providing appropriate care to patients most in need of skin cancer chemoprevention. Several studies have evaluated the efficacy of retinoids for chemoprevention of skin cancer. Thisstudysoughtto review all published literature on acitretin for KC chemoprevention, pool outcome data, and evaluate treatment costs in RTRs (see Supplemental Digital Content 1, Table S1, http://links.lww.com/DSS/A341). Downloaded from http://journals.lww.com/dermatologicsurgery by BhDMf5ePHKbH4TTImqenVA+lpWIIBvonhQl60EtgtdlLYrLzSPu+hQedJnbNaXBf on 01/29/2021 Downloaded from http://journals.lww.com/dermatologicsurgery by BhDMf5ePHKbH4TTImqenVA+lpWIIBvonhQl60EtgtdlLYrLzSPu+hQedJnbNaXBf on 01/29/2021 The prognosis of extraskeletal osteosarcomas, both primary and secondary, is extremely poor. [Extracted from the article]