Genomic Profiling Utility for Targeted Therapy Selection Shown in Advanced GI Cancers

Access to targeted therapies was similar for patients with gastrointestinal (GI) cancers and non-GI cancers who underwent genomic profile testing, according to findings published recently in Targeted Oncology.

With recent advancements in precision oncology enabling targeted therapy selection for several cancers via comprehensive genomic profiling (CGP), researchers note that CGP utility for advanced GI cancers, which are associated with a poor prognosis, remains unclear because of common nondruggable alterations and rapid disease progression that prevent a sufficient time period to seek targets.

“The median survival time of patients with advanced gastric, pancreatic, and biliary cancers is around 1 year even with standard treatments, which is extremely short compared with that of patients with non-GI cancers (such as breast and prostate cancers),” they explained. “Access to targeted therapies based on genomic profling in patients with GI cancer was reported to be 5%-7% in Japan, which is lower than what has been reported in whole cancer entities.”

The authors conducted a retrospective cohort study to further investigate the utility of genomic profling tests in patients with GI cancers. Their study population consisted of patients with GI cancers and non-GI cancers who underwent tissue-based genomic profling from April 2017 to October 2020 at St. Marianna University School of Medicine Hospital in Japan.

“The profle of gene alterations, frequency of tumor mutational burden-high (TMB-high; ≥ 10 muts/Mb), and accessibility of recommended molecular targeted therapy were compared between patients with GI cancers and patients with non-GI cancers,” said the study authors.

The tissue-based assays used for analysis were Oncomine Comprehensive Assay version 3,  FoundationOne CDx, NCC Oncopanel, PleSSision-160, and PleSSision-Exome. A total of 133 patients with GI cancers (most frequent: colorectal, 44%; pancreatic, 20%; gastric, 8%; esophageal, 8%) and 63 patients with non-GI cancers (most frequent: breast, 29%; ovarian, 14%; cervical, 13%; uterine, 8%) were included.

Among patients with GI cancers, genomic profiles showed the highest frequencies of TP53, KRAS, and APC mutations, and a signifcantly lower frequency of PIK3CA mutations compared with non-GI cancers. TMB-high was also found to be significantly less prevalent in GI vs non-GI cancers (4% vs 20%; P = .008).

Based on findings of the tissue-based assays, 29 patients with GI cancers (40%) and 35 patients with non-GI cancers (56%) were recommended for targeted therapies. Of these patients, 7 individuals from each group received the recommended therapy based on their genomic findings, exhibiting similar treatment accessibility between the GI and non-GI cancer groups (10% vs 11%; P = .791).

None of the patients with pancreatic cancer could access any targeted therapies. Human epidermal growth factor receptor 2 (HER2)-targeted and BRAF-targeted therapies were the primary treatments administered to patients with GI cancers.

“Despite their unfavorable genomic profles, patients with GI cancers were able to use targeted therapies similarly to patients with non-GI cancers,” concluded the researchers. “The utility of genomic profling in patients with GI cancers was highlighted to determine their opportunity to receive specific treatments, such as HER2-targeted and BRAF-targeted therapies.”

Reference

Takeda H, Imoto K, Umemoto K, et al. Clinical utility of genomic profling tests in patients with advanced gastrointestinal cancers. Target Oncol. Published online April 2, 2022. doi:10.1007/s11523-022-00871-4