The following article features coverage from the 2020 Gastrointestinal Cancers Symposium meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Results of a study involving comprehensive genomic profiling of a large number of biopsy specimens taken from patients with a diagnosis of advanced intrahepatic cholangiocarcinoma (IHCC) showed a higher frequency of genomic alterations in IDH1 and a lower frequency of a potentially targetable KRAS mutation in primary tumor specimens compared with specimens derived from metastatic lesions. The findings from this poster were presented at the 2020 Gastrointestinal Cancers Symposium held in San Francisco, California.

Although primary IHCC has been well characterized by comprehensive genomic profiling, less is known about the genomic characteristics of metastatic IHCC lesions.

In this study, comprehensive genomic profiling was performed on biopsy specimens from 1268 patients with advanced IHCC. The biopsy site was the primary tumor or a metastatic lesion (eg, lymph nodes, soft tissues, peritoneum, lung/pleura, omentum, bone, and other locations) in 1048 and 220 cases, respectively. DNA sequencing results also provided information on tumor mutational burden (TMB) and microsatellite instability (MSI) for both types of lesions, and immunohistochemistry was used to determine the level of programmed cell death ligand 1 (PD-L1) expression.

Similarities between the molecular landscapes of the 2 sets of samples included an average number of genomic alterations of approximately 4, as well as similar frequencies of MSI-high status, TMB-high status, and PD-L1 positivity.


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Notable differences in the genomic profiles of specimens taken from primary tumors compared with metastatic lesions included a higher frequency of genomic alterationsin IDH1 (16% vs 6%; P <.001), and a lower frequency of STK11 (2% vs 8%), in the former compared with the latter. IDH1 is a potentially targetable gene alteration and STK11 is a potential marker of resistance to immunotherapy.

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In addition, the frequency of KRAS alterations overall was 16% and 34% in primary and metastatic specimens, respectively (P <.001). Furthermore, the frequency of the potentially targetable KRAS G12C alteration in metastatic lesions was also found to be more than double that of the frequency of this mutation seen in primary lesions (2% vs <1%).

The authors reported that the metastatic-biopsy group “may contain a significant number of non-IHCC cases whose metastatic lesions were actually derived from other primary sites incorrectly assigned the diagnosis of IHCC.”

Disclosures: Foundation Medicine, Inc., funded this research, and some of the study authors disclosed financial relationships with pharmaceutical and medical device companies. For a full list of disclosures, please refer to the study abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO GI annual meeting by visiting the conference page.

Reference

Ross JS, Sokol E, Vergilio J-A, et al. Primary versus metastatic intrahepatic cholangiocarcinoma: A comparative comprehensive genomic profiling (CGP) study. J Clin Oncol. 2020;38(suppl 4):Abstract 578.