Unresectable Basal Cell Carcinoma Research Articles

Phase II, Single-Arm Trial of Induction and Concurrent Vismodegib With Curative-Intent Radiation Therapy for Locally Advanced, Unresectable Basal Cell Carcinoma.

Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatisfactory. Vismodegib is a hedgehog pathway inhibitor (HPI) active in BCC that may radiosensitize BCC. We evaluated the combination of vismodegib and RT for patients with LA BCC. In this multicenter, single-arm, phase II study, patients with unresectable LA BCC received 12 weeks of induction vismodegib, followed by 7 weeks of concurrent vismodegib and RT. The primary end point was LRC rate at 1 year after the end of treatment. Secondary end points included objective response, progression-free survival (PFS), overall survival (OS), safety, and patient-reported quality of life (PRQOL). Twenty-four patients received vismodegib; five were unable to complete 12 weeks of induction therapy. LRC was achieved in 91% (95% CI, 68 to 98) of patients at 1 year. The response rate was 63% (95% CI, 38 to 84) after induction vismodegib and 83% (95% CI, 59 to 96) after concurrent vismodegib and RT. With a median follow-up of 5.7 years, 1-year PFS and OS rates were 100% and 96%, and at 5 years PFS and OS rates were 78% and 83%, respectively. Distant metastasis or BCC-related death has not been observed. The most frequent treatment-related adverse events (AEs) were dysgeusia, fatigue, and myalgias occurring in 83%, 75%, and 75% of patients. No grade 4 to 5 treatment-related AEs occurred. PRQOL demonstrated clinically meaningful improvements in all subscales, with emotions and functioning improvements persisting for a year after the end of treatment. In patients with unresectable LA BCC, the combination of vismodegib and RT yielded high rates of LRC and PFS and durable improvements in PRQOL.

Hedgehog inhibitors with and without adjunctive therapy in treatment of locally advanced basal cell carcinoma

Hedgehog inhibitor therapy (HHIT) is considered first-line treatment for locally advanced, unresectable basal cell carcinoma (laBCC). HHIT often results in a partial response, which requires adjunctive therapy (AT) post HHIT. We present real-world data for laBCCs undergoing HHIT ± AT. Retrospective review at Duke University from 11/01/2007 through 5/20/2020 revealed 13 patients treated with systemic HHIT (sonidegib or vismodegib) for laBCC. Fourteen laBCCs were identified in 13 patients. LaBCCs were treated with sonidegib (n = 10, 71%) or vismodegib (n = 4, 29%) for a median (IQR) of 9.4 (9.3) or 9.8 (8.5) months, respectively. The median (IQR) follow-up time from HHIT initiation was 15.5 (8.7) months. Tumors were most often located on the trunk (43%), followed by head and neck (29%), extremities (21%), and orbit/periorbital area (7%). Nine laBCCs (64%) were treated with HHIT alone, of which five (36%) achieved complete response (CR), four (29%) achieved partial response (PR), and five (36%) achieved CR with combined HHIT and AT post-HHIT. Duration of HHIT treatment (IQR) was 7.5 (3.5) months in the 10 CR patients, versus 15.1 (6.3) months in the four PR patients (P = 0.024). Nine patients (69%) experienced adverse events from HHIT, most commonly ageusia/dysgeusia, muscle spasms, and alopecia. As a single institutional experience, we report 10/14 laBCCs (71%) with CRs without recurrence and 4/14 laBCCs (29%) with PRs with HHIT ± AT over median follow-up of 15.5 months. Longer follow-up and larger cohorts evaluating responses with HHIT followed by AT are needed to substantiate our findings.

Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma.

Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ≥65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age.