Sonidegib not affected by cardiovascular medications in locally advanced BCC

Sonidegib efficacy in patients with locally advanced basal cell carcinoma was not affected by concomitant cardiovascular medications, according to a presentation at Maui Derm for Dermatologists.

“Hedgehog inhibitors were developed to block aberrant Hedgehog signaling found in most sporadic BCCs; inhibition of the Hedgehog pathway is among the few treatment options available for patients with advanced BCC,” John Lear, MB, ChB, MD, FRCCP(UK), and colleagues wrote in the poster. “Many patients taking sonidegib also take multiple concomitant cardiovascular medications, which may affect the efficacy of sonidegib.”

Lear and colleagues presented a post hoc analysis of BOLT, a multicenter, randomized, double-blind phase 2 clinical trial. The study enrolled patients with locally advanced basal cell carcinoma (laBCC) that was “not amenable to curative surgery or radiation” or metastatic basal cell carcinoma “for which all other treatment options had been exhausted.” Researchers randomly assigned patients in a 1:2 ratio to sonidegib 200 mg daily or sonidegib 800 mg daily. Among 79 patients (median age, 67 years; men, 48) assigned to sonidegib 200 mg, 66 had laBCC; of those, 29 received some form of concomitant cardiovascular medication (angiotensin II antagonist, three; ACEI, 13; direct thrombin inhibitor, four; HMG CoA reductase inhibitor, nine).

The objective response rate among patients with laBCC taking concomitant cardiovascular medications (angiotensin II antagonist, ORR = 66.7; 95% CI, 9.4-99.2; ACEI, ORR = 92.3; 95% CI, 64.0-99.8; direct thrombin inhibitor, ORR = 75.0; 95% CI, 19.4-99.4; HMG CoA reductase inhibitor, ORR = 77.8; 95% CI, 40.0-97.2) was “comparable” to all patients (ORR = 71.2; 95% CI, 58.7-81.7) with laBCC.

At 42 months, 97% of patients with laBCC experienced an adverse event. The researchers wrote that the majority of adverse events were grade 1 to 2, with the most frequent events including muscle spasms (54.4%), alopecia (49.4%), dysgeusia (44.3%) and nausea (39.2%).

“Sonidegib 200 mg daily led to clinically meaningful outcomes in patients with laBCC through 42 months of treatment, with a manageable tolerability profile,” the researchers wrote. “Efficacy of sonidegib 200 mg daily was not impacted by concomitant CV medication usage.”