Long-term results of investigator-assessed efficacy and safety of 200mg dose of sonidegib for locally advanced basal cell carcinoma: 30-month BOLT analysis

Long-term results of investigator-assessed efficacy and safety of 200mg dose of sonidegib for locally advanced basal cell carcinoma: 30-month BOLT analysis

Presenters: Migden M¹, Lewis KD²

Affiliations: ¹University of Texas MD Anderson Cancer Center, Departments of Dermatology, Division of Internal Medicine, and Head and Neck Surgery, Division of Surgery, Houston, TX; ²University of Colorado Denver, School of Medicine, Division of Medical Oncology, Denver, CO

Background/Objective: The 200mg dose of sonidegib was approved in 2015 in the European Union, Switzerland, Australia, and the United States for the treatment of patients with locally advanced basal cell carcinoma (laBCC) who are not amenable to curative surgery or radiation therapy. In both Switzerland and Australia, sonidegib is also approved for the treatment of metastatic BCC (mBCC). Sonidegib is a selective smoothened (SMO) inhibitor that blocks hedgehog pathway signaling. Approvals were based on results from the pivotal BOLT Phase II clinical trial (NCT01327053). Efficacy and safety data from BOLT were assessed by both investigator and central review. Here, we report the investigator-assessed efficacy and safety data of sonidegib 200mg QD from the 30-month analysis.

Methods: BOLT is a randomized, double-blind clinical trial that was conducted in 58 centers across 12 countries. Patients received either 200mg or 800mg of sonidegib once daily. Only the 200mg dose data will be presented here, as this dose was found in earlier studies to be more tolerable and equally as effective as the higher dose. As a primary endpoint, investigators evaluated objective response rate (ORR), which is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor evaluations were done using BCC-modified Response Evaluation Criteria In Solid Tumors (mRECIST) for laBCC. Sonidegib safety was monitored, including the monitoring of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.

Results: In patients with laBCC who received sonidegib 200mg (n=66), the investigator-assessed ORR was 71 percent. Median overall survival was not reached at this time point, but the two-year overall survival rate was 93 percent. Tumor responses were durable with a median duration of response of 15.7 months. At the 30-month data cutoff, the median duration of PFS was 19.4 months. One death was reported in the 200mg dose arm of patients with laBCC, but it was not considered to be related to study treatment. The safety profile of sonidegib 200mg was manageable, and no new safety concerns were found compared to the earlier BOLT data analyses. In summary, 43 percent of patients experienced grade 3/4 adverse events and AEs requiring dose interruptions/reductions. AEs that led to discontinuation occurred in 30 percent of patients, and the most commonly reported AEs included muscle spasms (56%), alopecia (52%), and dysgeusia (47%).

Conclusion: In the BOLT 30-month analysis, sonidegib 200mg QD provided sustained efficacy and a continued long-term acceptable safety profile in patients with laBCC. Interestingly, both the median DOR and median PFS data were higher when assessed by central review compared to investigator review. Given the stringent criteria used to assess tumor responses in the BOLT trial, these data support the use of sonidegib 200mg QD in patients with laBCC when used according to local treatment guidelines.