Basal cell carcinomas (BCCs) exhibit aberrant activation of the hedgehog pathway.,Sonidegib is a hedgehog pathway inhibitor approved for the treatment of locally advanced BCC (laBCC) and metastatic BCC (mBCC) based on primary results of the BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment].,This is the final 42‐month analysis of the BOLT study, evaluating the efficacy and safety of sonidegib.,Adults with no prior hedgehog pathway inhibitor therapy were randomized in a 1 : 2 ratio to sonidegib 200 mg or 800 mg once daily.,Treatment continued for up to 42 months or until disease progression, unacceptable toxicity, death, study termination or withdrawal of consent.,The primary efficacy end point was the objective response rate (ORR) by central review, assessed at baseline; weeks 5, 9 and 17; then subsequently every 8 or 12 weeks during years 1 or 2, respectively.,Safety end points included adverse event monitoring and reporting.,The study enrolled 230 patients, 79 and 151 in the 200‐mg and 800‐mg groups, respectively, of whom 8% and 3.3% remained on treatment by the 42‐month cutoff, respectively.,The ORRs by central review were 56% [95% confidence interval (CI) 43-68] for laBCC and 8% (95% CI 0·2-36) for mBCC in the 200‐mg group and 46·1% (95% CI 37·2-55·1) for laBCC and 17% (95% CI 5-39) for mBCC in the 800‐mg group.,No new safety concerns emerged.,Sonidegib demonstrated sustained efficacy and a manageable safety profile.,The final BOLT results support sonidegib as a viable treatment option for laBCC and mBCC.,What's already known about this topic?,Basal cell carcinoma (BCC) is usually treatable with surgery or radiation therapy, but there are limited treatment options for patients with advanced BCC.Sonidegib, a hedgehog pathway inhibitor approved for the treatment of advanced BCC, demonstrated clinically relevant efficacy and manageable safety in prior analyses of the phase II randomized, double‐blind BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment].,Basal cell carcinoma (BCC) is usually treatable with surgery or radiation therapy, but there are limited treatment options for patients with advanced BCC.,Sonidegib, a hedgehog pathway inhibitor approved for the treatment of advanced BCC, demonstrated clinically relevant efficacy and manageable safety in prior analyses of the phase II randomized, double‐blind BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment].,What does this study add?,This final 42‐month analysis of BOLT is the longest follow‐up available for a hedgehog pathway inhibitor.Clinically relevant efficacy results were sustained from prior analyses, with objective response rates by central review of the approved 200‐mg daily dose of 56% in locally advanced BCC and 8% in metastatic BCC.No new safety concerns were raised.The results confirmed sonidegib as a viable long‐term treatment option for patients with advanced BCC.,This final 42‐month analysis of BOLT is the longest follow‐up available for a hedgehog pathway inhibitor.,Clinically relevant efficacy results were sustained from prior analyses, with objective response rates by central review of the approved 200‐mg daily dose of 56% in locally advanced BCC and 8% in metastatic BCC.,No new safety concerns were raised.,The results confirmed sonidegib as a viable long‐term treatment option for patients with advanced BCC.,Linked Comment:Fife.,Br J Dermatol 2020; 182:1322-1323.
Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498).,Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).,The primary objective for each group was objective response rate (ORR) per independent central review (ICR).,Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.,For Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively.,ORR per ICR was 41.1% (95% CI, 28.1% to 55.0%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 45.2% (95% CI, 35.9% to 54.8%) in both groups combined.,Per ICR, Kaplan-Meier estimate for DOR at 8 months was 95.0% (95% CI, 69.5% to 99. 3%) in responding patients in Group 3, and at 12 months was 88.9% (95% CI, 69.3% to 96.3%) in responding patients in Group 1.,Per INV, ORR was 51.8% (95% CI, 38.0% to 65.3%) in Group 3, 49.2% (95% CI, 35.9% to 62.5%) in Group 1, and 50.4% (95% CI, 41.0% to 59.9%) in both groups combined.,Overall, the most common adverse events regardless of attribution were fatigue (27.0%) and diarrhea (23.5%).,In patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile.,Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.,Clinicaltrials.gov, NCT02760498.,Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498