The following is a summary of “Comprehensive genomic profiling of advanced anal adenocarcinoma,” published in the January 2024 issue of Oncology by Ogura, et al.

Anal adenocarcinoma (anal AD) is a rare and aggressive gastrointestinal malignancy lacking established standard therapy. Treatment strategies are often extrapolated from advanced rectal adenocarcinoma (rectal AD) due to its rarity. Limited knowledge exists regarding genetic alterations (GAs) and their therapeutic implications in advanced anal AD. For a study, researchers sought to investigate and compare the genomic profiles of advanced anal AD with advanced rectal AD.

Retrospective data from patients with advanced anal AD and rectal AD, who underwent comprehensive genomic profiling (CGP) tests and were registered with the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) in Japan, were extracted. CGP tests were conducted using NCC Oncopanel or FoundationOne CDx. Somatic GAs, microsatellite instability (MSI) status, tumor mutation burden (TMB), actionable GAs, and druggable GAs were examined.

Between June 2019 and April 2023, 45 patients with anal AD and 1,915 patients with rectal AD were enrolled in the C-CAT database. In anal AD, common actionable GAs included TP53 (89%), KRAS (51%), ERBB3 (22%), MYC (20%), SMAD4 (20%), and ERBB2 (11%). Anal AD showed a significantly higher frequency of actionable GAs in ERBB3 (22% vs. 2%, p < 0.01), MYC (20% vs. 8%, P< 0.01), and BRCA2 (7% vs. 1%, P < 0.01), and a significantly lower frequency in APC (7% vs. 85%, P < 0.01) compared to rectal AD. MSI-high and TMB-high proportions did not significantly differ between anal AD and rectal AD (P = 0.79 and P = 0.54, respectively). Druggable GAs in anal AD included KRAS G12D mutation (22%), ERBB2 amplification (7%), BRCA2 mutation (7%), and BRAF V600E mutation (2%). Anal AD exhibited a significantly higher frequency of druggable GAs in BRCA2 mutation compared to rectal AD (7% vs. 1%, P < 0.01).

The study revealed distinct genomic profiles in anal AD compared to advanced rectal AD. Comprehensive genomic profiling is valuable in identifying druggable GAs in advanced anal AD, providing expanded therapeutic opportunities.

Reference: ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.4