Advanced Basal Cell Cancer: Concise Review of Molecular Characteristics and Novel Targeted and Immune Therapeutics

M. Nikanjam; P. R. Cohen; S. Kato; J. K. Sicklick; R. Kurzrock


Ann Oncol. 2018;29(11):2192-2199. 

In This Article

Illustrative Patient Report: Advanced BCC With PTCH1 Mutation and High TMB

A 62-year-old Caucasian man presented with a 13-month history of a growing, large mass on his upper back (10 × 8 × 2.5 cm) (Figure 2A–C). Imaging with positron emission tomography (PET) and computed tomography (CT) scans showed no definitive metastatic disease. Pathology was consistent with advanced nodular basal cell carcinoma (Figure 2D–E). Genomic molecular testing [Foundation Medicine ( NGS of 315 genes)] of the carcinoma demonstrated a very high tumor mutation burden (53 mutations per megabase, with ≥ 20 mutations/megabase considered to be very high in oncology); the patient also had 11 genomic variants of known significance including PTCH1 (splice site 1504–1G>T), ASXL1 Q760, INPP4B W521, KEL R130Q, PIK3R1 R534, PTEN (splice site 210 2A>T), RAC1 P29S, TERT promoter-124C>T, TP53 R196, TP53 Q100, and WT1 C350R. After obtaining consent on the precision medicine protocol, I-PREDICT (Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy; NCT02534675) at our Center for Personalized Cancer Therapy, he was started on the oral Hedgehog inhibitor vismodegib 150 mg daily with nivolumab [checkpoint (PD-1) inhibitor immunotherapy] initiated 1 week later for four total doses (240 mg i.v. for three doses; 120 mg for final dose). Nivolumab was stopped after the fourth dose because he required steroids for grade 3 skin rash and developed recurrent transaminitis (which resolved after immunotherapy was discontinued). He attained a CR after 5 months of treatment (Figure 2F–G). Four skin biopsies from the previously affected area showed no microscopic evidence of disease. Vismodegib was administered for a total of 8.5 months and then stopped because of loss of appetite (and because the patient had achieved a CR). Follow-up imaging with PET/CT scan remained negative for metastatic disease. Currently, he has been off therapy for 12 months with ongoing CR 20 months from the time treatment was initiated. We cannot know for certain which drug (or whether it is the combination of nivolumab and vismodegib) that mediated the patient's exceptional response. Nevertheless, vismodegib alone has a CR rate of only about 7%,[36] with about 40% of patients who achieve CR being able to maintain the remission for the long term, and higher risk of relapse in individuals with tumors outside of the head and neck region (as found in our patient).[66] Therefore, a CR lasting for 20 months, including 12 months off of therapy, would be expected to occur in <3% of patients with advanced basal cell carcinoma of the trunk treated with vismodegib alone.

Figure 2.

Patient with advanced giant nodular basal cell carcinoma. (A–C) Initial clinical presentation with large exophytic tumor of the left back. (D, E) Pathology demonstrated hemorrhagic crust with nodular aggregates of basaloid tumor cells with cytologic atypical and peripheral palisading of the basal cells extending from the overlying eroded epithelium into the dermis. (F, G) Five months after therapy initiation. Complete response after treatment with vismodegib 150 mg by mouth daily and four doses of nivolumab. Patient remains in complete remission at 20+ months.