(P-574) Frequency, Characteristics, and Subsequent Treatment (Tx) of Real-world Patients (pts) Who Discontinue Hedgehog Inhibitors (HHIs) as First-line (1L) Systemic Tx for Advanced Basal Cell Carcinoma (aBCC)

Background: HHIs are the only approved 1L systemic Tx for aBCC and Tx options following HHI Tx failure are limited.

Objectives: To assess frequency, characteristics, and subsequent Tx patterns of pts with aBCC discontinuing 1L HHIs due to toxicity or disease progression.

Methods: We conducted a retrospective cohort study using electronic health records of pts treated in The US Oncology Network (Network), a community-based network of >450 oncology clinics. We identified adults (18+ years) with aBCC, not treated for another primary malignancy in the past 3 years, with ≥2 Network visits who discontinued 1L HHI monotherapy between January 2012 and November 2019 due to documented toxicity or progression without evidence of complete response (CR) who subsequently initiated second-line (2L) systemic Tx (2L initiators) or not (2L non-initiators). To exclude pts potentially using neoadjuvant HHIs, we required 2L non-initiators to be followed for ≥90 days after HHI discontinuation and excluded pts who underwent surgery or radiation during this period. Index date was Tx initiation for 2L initiators and 90 days after HHI discontinuation for 2L non-initiators. We describe cohort attrition and characteristics of 2L initiators and 2L non-initiators as well as Txs initiated among 2L initiators.

Results: Among 138 aBCC pts treated with HHIs regardless of line of therapy with fully accessible charts: 115/138 (83.3%) received HHIs as 1L systemic aBCC therapy; 73/115 (63.5%) discontinued 1L HHIs; 37/73 (50.7%) discontinued due to documented toxicity or progression without evidence of CR. 4/37 pts (10.8%) initiated 2L systemic Tx (1 carboplatin & paclitaxel; 1 cemiplimab; 1 nivolumab; 1 pembrolizumab) within a median (range) of 75 days (2‒130) from HHI discontinuation. 2L initiators were 68.7 years of median age (48.4‒71.1); 100% female; 75% White; 75% immunocompetent; 100% treated with 1L vismodegib for a median of 8.6 months (6.8‒42.2); 100% discontinued 1L HHIs due to documented disease progression. We identified 15 2L non-initiators; median age 80.2 years (49.6‒90+); 20% female; 100% White; 86.7% immunocompetent; 100% treated with 1L vismodegib for a median of 6.8 months (1.9‒20.6); 93.3% discontinued 1L HHIs due to documented toxicity and 6.7% due to progression.

Conclusions: In this small cohort of aBCC pts discontinuing 1L HHIs, ~50% discontinued due to toxicity or disease progression. There was no standard of care after HHI Tx failure with only a minority of pts initiating 2L Tx. Effective Tx strategies for pts who do not respond to or cannot tolerate HHIs are needed.