RESUMEN
Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC.
RESUMEN
BACKGROUND: Comprehensive cancer genomic profiling has been used recently for patients with advanced solid cancers. Two cancer genomic profiling tests for patients with no standard treatment are covered by Japanese public health insurance since June 2019. METHODS: We prospectively analyzed data of 189 patients with solid cancers who underwent either of the two-cancer genomic profiling tests at Hokkaido University Hospital and its liaison hospitals and whose results were discussed in molecular tumor board at Hokkaido University Hospital between August 2019 and July 2020. RESULTS: All 189 patients had appropriate results. Actionable gene alterations were identified in 93 patients (49%). Frequent mutations included PIK3CA (12%) mutation, BRCA1/2 alteration (7%), ERBB2 amplification (6%) and tumor mutation burden-High (4%). The median turnaround time from sample shipping to acquisition by the expert panel was 26 days. Although 115 patients (61%) were provided with information for genotype-matched therapies, only 21 (11%) received them. Notably, four of eight patients below the age of 20 years were provided information for genotype-matched therapies, and three received them. Their response rates and disease control rates were 29% and 67%, respectively. Most patients who did not undergo the genotype-matched therapies were provided information for only investigational drugs in phases I and II at distant clinical trial sites in central Japan. Twenty-six patients were informed of suspected germline findings, while 11 patients (42%) received genetic counseling. CONCLUSIONS: The publicly reimbursed cancer genomic profilings may lead to the modest but favorable therapeutic efficacy of genotype-matched therapy for solid cancer patients with no standard therapy. However, poor access to genotype-matched therapy needs to be resolved.