Sonidegib, a hedgehog pathway inhibitor (HPI), is approved in the United States and European Union for locally advanced basal cell carcinoma (laBCC) based on primary results from the BOLT trial (Migden, Lancet, 2015). Updated data from 30-months analysis demonstrated continued efficacy and manageable safety (Dummer ASCO 2016). Here we present 30-month tumor burden results, which have not previously been presented or published.
Eligible HPI-treatment-naïve patients with laBCC not amenable to curative surgery/radiotherapy or patients with metastatic BCC (mBCC) were randomized 1:2 to receive sonedegib 200 or 800 mg QD. For all patients, tumor burden was assessed as decrease of best percentage change from baseline by central review. For patients with laBCC, tumor lesions were assessed by photography and modified RECIST criteria; for patients with mBCC, photography or MRI/computed tomography (CT) and RECIST 1.1 were used.
Evaluable patients at 30 months were from the primary efficacy analysis set (pEAS) for laBCC patients (200 mg, n = 32; 800 mg, n = 74) and mBCC patients (200 mg, n = 12; 800 mg, n = 19). Consistent with the primary, 12- and 18-month analyses, 96.9% (n = 31) and 94.6% (n = 70) of patients with laBCC experienced a substantial reduction in tumor size with sonidegib 200 and 800 mg, respectively. Reduction in target lesions for patients with mBCC receiving 200 mg was 91.7% (n = 11) across all time points; for the 800 mg group, 84.2% (n = 16) of patients experienced reduction in tumor lesions in the primary, 12-, 18-month analyses and 89.5% (n = 17) at 30 months. Sonidegib 200 mg had a more favorable safety profile compared to 800 mg, with lower rates of grade 3/4 adverse events (AEs; 43.0% vs 64.0%) and AESs events leading to discontinuation (30.4% vs 40.0%).
Sonedegib 200 and 800 mg in patients with laBCC and mBCC demonstrated substantial target tumor lesion reduction across 30 months. Safety/tolerability was manageable and similar across 30 months with no new side effects emerging following the primary analysis.
Clinical trial identification
Legal entity responsible for the study
Sun Pharmaceutical Industries Ltd.
R. Dummer: Received research funding from Novartis, Merck, Bristol-Myers Squibb, Roche, and GlaxoSmithKline and has served as a consultant/advisory board for Novartis, Merck, Bristol-Myers Squibb, Roche, GlaxoSmithKline, Amgen, and Takeda. M. Migden: Participated on advisory boards and received honoraria from Genentech, Inc.; Novartis Pharmaceuticals Corporation; Eli Lilly and Company; and Sun Pharmaceuticals