205 Background: Anaplastic lymphoma kinase (ALK) fusions are well‐established therapy targets in non‐small cell lung cancer but can also occur in other tumor types. In colorectal cancer (CRC), ALK fusions were first described in 2012, and have since been detected by both tissue and liquid biopsies and linked to response to ALK inhibitors. This study characterizes the genomic and clinical features of ALK fusions in CRC. Methods: 56,206 advanced (stage III 1-49% = low positive and >50% = high positive). Results: 63 (0.1%) CRC tumors featured ALK fusions (ALKfus+). In contrast to CRC tumors negative for ALK fusions (ALKfus-), ALKfus+ CRC were older (median age 68 years vs 62 years; p=.012) and less frequently male gender (34.9% vs 56.0%; p20 mutations/Mb (28.6% vs 6.3%; p<.0001) and PD-L1 expression (23.7% vs 14.9%; NS). KRAS mutations are less frequently identified in ALKfus+ CRC (9.5% vs 48.6%; p<.0001), and APC mutations (31.7% vs 78.3%; p<.0001). Targetable mutations including BRAF V600E (6.3% vs 10.7%; NS) and ERBB2 (1.6% vs 5.3%; NS) were less frequent in ALKfus+ CRC. HRDsig+ status was extremely uncommon in both groups (0.0% vs 1.7%; NS). GA in TP53 were similar (74.6% vs 76.2%; NS). Non-fusion ALK GA were identified in 0.3% of ALKfus- CRC. Additional noteworthy GA with differences in frequency between ALKfus+ and ALKfus- CRC are summarized in Table 1. Conclusions: ALK fusions are uncommon in CRC but are associated with enrichment of IO response markers and fewer mutations in genes commonly targeted in CRC. This may represent a distinct therapeutic opportunity to treat ALKfus+ CRC with both ALK-directed targeted therapy and immunotherapy. Noteworthy GAs differentially observed in ALKfus+ vs ALKfus- CRC. Genes* ALKfus+ ALKfus- P-value † ARID1A 22.2% 8.2% 0.002 NF1 12.7% 2.9% 0.002 PTCH1 9.5% 1.7% 0.003 ASXL1 14.3% 5.2% 0.014 SMARCA4 7.9% 1.8% 0.014 BRCA2 9.5% 3.0% 0.027 CDH1 6.3% 1.6% 0.038 CDKN2A 7.9% 2.9% 0.064 PIK3CA 0.0% 18.9% <.0001 *Genes only included if seen at ≥5% in any population. † False discovery rate (FDR) corrected using Benjamini-Yekutieli procedure.
Li et al. (Sat,) studied this question.