Outcomes in patients (pts) with advanced basal cell carcinoma (aBCC) who discontinued hedgehog inhibitors (HHI) as first-line (1L) systemic treatment (Tx) in a US community oncology setting: A retrospective observational study.

e18742 Background: HHIs are the only approved 1L systemic Tx for aBCC. Many pts develop resistance or are intolerant to HHIs and may require second-line (2L) Tx. Little is known about patient outcomes following HHI discontinuation. In this study, we describe characteristics and outcomes among pts with aBCC who discontinued 1L HHIs due to progression or toxicity. Methods: In this retrospective cohort study, we identified adult pts diagnosed with aBCC who discontinued 1L HHI monotherapy between January 2012 and November 2019 in The US Oncology Network (Network), a community-based network of > 450 oncology clinics. Pts with ≥2 Network visits and no Tx for other primary malignancy 3 years prior to index date were included. Structured and unstructured data in the electronic health records were used to extract information on pt characteristics and outcomes. Pts were grouped based on initiation of 2L systemic Tx post-HHI discontinuation into 2L initiators and 2L non-initiators. 2L non-initiators were followed for ≥90 days post-HHIs discontinuation, and those undergoing surgery or radiation during this period (i.e. potential neoadjuvant HHI use) were excluded. Index date was date of 2L Tx initiation for 2L initiators and 90 days post 1L HHI discontinuation for 2L non-initiators. Pts were followed from index date until death, Tx initiation for another primary cancer, loss to follow-up, or end of study (February 1, 2020), whichever occurred first. Pt disposition and outcomes were described separately for each group. Results: We identified 73 aBCC pts who discontinued 1L HHI monotherapy during the specified period. Of those, 19 (26%) pts (4 [21%] 2L initiators and 15 [79%] 2L non-initiators) were included in the study: 12 (63%) were male and 3 (21%) were metastatic at diagnosis, with a mean age of 73 years. Median (range) follow-up time from index date was 10 (3‒42) months for 2L non-initiators and 6 (1‒61) months for 2L initiators. Fourteen (74%) pts discontinued HHI due to toxicity (all 2L non-initiators) and 5 (26%) due to progression (4 2L initiators and 1 2L non-initiator). Median time to discontinuation of 1L HHI was 7 (2‒9) months in 2L non-initiators and 9 (7‒42) months in 2L initiators. 2L initiators received subsequent Tx 2‒130 days following discontinuation of 1L HHI. Time to discontinuation of 2L Tx ranged 4–11 months. Six deaths (32%) were observed during study period (5 2L non-initiators and 1 2L initiator). Conclusions: The short duration of 1L HHI Tx in our small cohort of aBCC pts who did not respond to and/or tolerate HHI is consistent with previous findings. During the study period, limited therapeutic options existed post-HHI, highlighting the unmet need for more effective Tx strategies in a 2L aBCC setting.