Intermittent dosing of vismodegib (Erivedge) for locally advanced/metastatic basal cell carcinoma appears to preserve efficacy, but reduces treatment-related side effects, according to Kishwer Nehal, MD, director of Mohs micrographic and dermatologic surgery at Memorial Sloan Kettering Cancer Center, New York.

That’s important because, although some patients have a good response to vismodegib, more – about 80% – have side effects that make it necessary to stop treatment, including muscle spasms and weight loss, among other problems. Side effects often come on quickly and can become intolerable after a few months of treatment, so physicians have looked for alternative dosing regimens to hold them off, with some success.

Dr. Kishwer Nehal
Dr. Kishwer Nehal
At the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation, Dr. Nehal reviewed a trial of 229 patients with six or more basal cell carcinomas (BCCs), published in 2017. They had 8-week drug holidays between either 12 or 24 weeks of treatment with vismodegib (150 mg by mouth daily); the treatment-placebo cycles went on for 73 weeks. Results were compared with continuous-dosing data in a large vismodegib safety trial.

Compared with those on continuous dosing, fewer patients on intermittent dosing discontinued treatment for adverse events (23% versus 31%). Patients on intermittent dosing also experienced fewer grade 3 adverse events (31% versus 44%) and were on treatment for a longer period of time (a median of 71.4 weeks versus 37.6 weeks).

Meanwhile, among those on intermittent dosing, the number of BCCs was reduced in more than half of the patients in both interrupted treatment groups, but more so in the 12-weeks-on/8-weeks-off group (Lancet Oncol. 2017 Mar; 18[3]:404-12).

Other treatment options are being explored for vismodegib, as well as for sonidegib (Odomzo), another hedgehog signaling pathway inhibitor approved for advanced BCC. Ongoing trials are looking at the use of hedgehog inhibitors with radiation, and for shrinking tumors before surgery, Dr. Nehal said

For now, however, surgery remains the mainstay of treatment for BCC; both biologics are indicated for when other treatments fail or are not feasible. For high-risk BCC (meaning high risk for recurrence, based on infiltrative or poorly defined histology, perineural or bony involvement, or location on the face, for instance), “surgery with clear margins remains the goal and is the most effective treatment. For a high-risk [BCC], you pretty much need surgery,” she said.

Recurrence is less likely with Mohs surgery than with standard excision. When Mohs isn’t available, “you should wait for the pathology report before reconstruction,” she said.

“Radiation for high-risk [BCC] is really reserved for nonsurgical candidates,” Dr. Nehal commented. There are only two scenarios to consider radiation in high-risk BCC, “and they really have no proven benefit in any sort of prospective trial. One is if you cannot, after exhaustive surgery, clear your very high risk [BCC].” The other is if there is “really large nerve involvement, greater than 0.1 mm, or such extensive perineural involvement that surgery is unlikely to be successful,” she said.

Dr. Nehal had no relevant disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.