Vismodegib offers promise for basal cell carcinoma, with caveats



SAN DIEGO – Patients treated with vismodegib for locally advanced or metastatic basal cell carcinoma went a median of 15 months before their disease progressed or they stopped treatment because of side effects, according to a 30-month update of the pivotal ERIVANCE basal cell carcinoma study.

Median progression-free survival on the first-in-class oral hedgehog-pathway inhibitor was 9 months, reported Dr. Seaver Soon at the annual meeting of the American Society for Dermatologic Surgery.

Data from two other trials of vismodegib resemble results from ERIVANCE, added Dr. Soon, a dermatologist in private practice in La Jolla, Calif. An expanded access study (J. Am. Acad. Dermatol 2014;70:60-9) of 119 patients with advanced basal cell carcinoma (BCC) reported comparable objective response rates (46.4% for patients with locally advanced BCC and 30.8% for patients with metastatic disease), and an interim analysis of data from the STEVIE trial had findings that were “very similar” to ERIVANCE, he said.

Dr. Seaver Soon

Dr. Seaver Soon

Thus far, vismodegib “offers a hope in treating otherwise difficult to manage, unresectable basal cell carcinoma tumors,” said Dr. Iren Kossintseva, a dermatologist in Vancouver, B.C. But the drug “may not be as tissue sparing as promised, she added. In a patient with chronic lymphocytic leukemia who had a large BCC on his lower eyelid and cheek, 7.5 months of vismodegib reduced the exophyticity and erosiveness of the tumor, but “likely did not substantially reduce the overall extent of necessary reconstruction,” she reported.

Vismodegib can cause potentially severe side effects. All seven patients who Dr. Kossintseva treated with 150 mg vismodegib per day during 2013-2014 developed “notable” adverse effects – including polycyclic rash, sensory and motor problems within the tumor area, bilateral edema of the lower limbs, congestive heart failure, and renal failure that has been slow to improve after stopping vismodegib, she said. “These are unique patients, and it’s often an uphill battle with these patients,” she added.

Tumors also can exhibit primary and secondary resistance to vismodegib, Dr. Soon noted. Studies have shown primary resistance characterized by tumor progression after as little as 2 months of treatment (Mol. Oncol. 2014; S1574-7891:00216-6) while secondary (or acquired) resistance occurs after an initial response to treatment and is linked to a mutation that interferes with drug binding, he said. Acquired resistance typically occurs when patients have been on vismodegib for about a year, Dr. Soon added. “Concurrent treatment with an alternative smoothened inhibitor, such as itraconazole, and downstream target inhibitors may overcome resistance,” he said. Dr. Kossintseva declared no conflicts of interest. Dr. Soon reported receiving honoraria and research grants from Genentech, the maker of vismodegib.

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