Vismodegib induces long-term response after discontinuation in locally advanced basal cell carcinoma
A substantial proportion of patients with locally advanced basal cell carcinoma demonstrated long-term responses to vismodegib after discontinuation of the drug, according to results of a retrospective study published in Journal of Clinical Oncology.
Researchers also found that most patients who relapsed after discontinuation responded to retreatment with vismodegib (Erivedge, Genentech), a hedgehog pathway inhibitor.
“Locally advanced basal cell carcinomas are complex and heterogeneous tumors for which surgery or radiotherapy might be contraindicated or inappropriate,” Florian Herms, MD, medical oncologist at Hospital Saint-Louis in France, and colleagues wrote. “Until recently, limited therapeutic options were available for these cancers, with a high morbidity and a profound psychological burden.”
Daily vismodegib, dosed at 150 mg orally, demonstrated clinical efficacy in phase 1 and phase 2 trials, with investigator-assessed objective response rates ranging from 60.3% (95% CI, 47.2-71.7) at 39 months to 68.5% (95% CI, 65.7-71.3) at median follow-up of 17.9 months. This included partial response rates of 28.6% to 35.1% and complete response rates of 31.7% to 33.4%.
Herms and colleagues evaluated the relapse rate after vismodegib discontinuation among 116 patients (median age, 73 years; range, 58.8-82.3; 57.8% men) with locally advanced basal cell carcinoma at nine French oncodermatology units who achieved complete response and stopped treatment between March 2012 and January 2016. Median time to complete response was 6 months (interquartile range [IQR], 4.2-8.6 months) and median treatment duration was 8.4 months (IQR, 6.1-12.2 months).
Among all patients, 14 received radiotherapy and one received chemotherapy before vismodegib.
Most patients (74.1%) stopped vismodegib because of adverse events.
Median RFS served as the study’s primary endpoint. Secondary endpoints included 3-year RFS, 3-year OS, 3-year cumulative incidence of relapse and assessment of treatment modalities after relapse.
Results showed median RFS of 18.4 months (95% CI, 13.5-24.8), with 36-month RFS rates of 35.4% (95% CI, 22.5-47.9) for the total population and 40% (95% CI, 25.7-53.7) after excluding 18 patients with Gorlin syndrome.
Median OS was not reached. However, researchers observed an OS rate at 36 months of 85% (95% CI, 74.6-96).
The rate of 3-year cumulative incidence of relapse was 59% (95% CI, 48.5-70), including 35 patients with focal relapse and 19 patients with multifocal relapse.
Locally advanced basal cell carcinoma to the limbs and trunk appeared to be the only factor independently associated with higher risk for relapse (HR = 2.77; 95% CI, 1.23-6.22).
Twenty-seven of the 54 patients who experienced relapse during follow-up received retreatment with vismodegib. Among them, 23 (85%) had an objective response to the drug, including 37% with complete response and 48% with partial responses. Twenty-four retreated patients became eligible for surgery.
The study’s retrospective nature served as its primary limitation. Researchers also acknowledged the difficulty assessing diagnosis of complete response, which may have resulted in overestimation of incidence among complete responders.
“We present here, to our knowledge, the first multicenter study that evaluates the durability of complete response for locally advanced basal cell carcinoma after discontinuation of the hedgehog pathway inhibitor vismodegib,” Herms and colleagues wrote. “These data underline the major benefit of vismodegib treatment of patients with nonsurgically resectable locally advanced basal cell carcinoma, particularly elderly patients or those with multiple comorbidities for whom the tumor burden can be life-threatening.” – by John DeRosier
Disclosures: Herms reports consultant/advisory roles with Aventis and Sanofi and travel expenses from Sun Pharmaceutical Industries. Please see the study for all other authors’ relevant financial disclosures.