Abstract 926P
Background
Cancer of unknown primary remains a challenging clinical entity. Despite receiving empiric chemotherapy, median overall survival is approximately 6 to 12 months. Site-specific therapy based on molecular characterization has shown to improve outcomes. However, feasibility outside of clinical trials, especially in community centres, is lacking. This study explores the application of rapid next-generation sequencing in defining cancer of unknown primary and to identify therapeutic biomarkers.
Methods
A retrospective chart review was performed by identifying pathological samples designated cancer of unknown primary. Next-generation sequencing testing was based on an automated workflow utilizing the Genexus integrated sequencer, validated for clinical use. Genomic profiling was further integrated within a routine immunohistochemistry service, with results reported directly by anatomic pathologists.
Results
Between October 2020 and October 2021, 578 solid tumor samples underwent genomic profiling. Among this cohort, 40 were selected based on an initial diagnosis of cancer of unknown primary. The median (range) age at diagnosis was 70 (42-85) and 23 (57%) were female. Genomic data were utilized to support a site-specific diagnosis in 6 patients (15%). Median turnaround time was 3 business days (IQR: 1-5). Most common alterations identified were KRAS (35%), CDKN2A (15%), TP53 (15%), and ERBB2 (12%). Actionable molecular targeted therapies were identified in 23 (57%) patients, including alterations in BRAF, CDKN2A, ERBB2, FGFR2, IDH1, and KRAS. Immunotherapy sensitizing deficient mismatch repair was identified in 1 patient.
Conclusions
This study supports the adoption of rapid next-generation sequencing among patients with cancer of unknown primary. We demonstrate the feasibility of integration of genomic profiling with diagnostic histopathology and immunohistochemistry. We propose a new diagnostic algorithm incorporating genomic profiling to better define cancer of unknown primary for future study as well as to identify actionable molecular targets.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
B. Sheffield: Financial Interests, Personal and Institutional, Sponsor/Funding: Amgen, AstraZeneca, Bayer, Biocartis, Boehringer-Ingelheim, Cell Marque, Elevation Oncology, Ely Lily, EMD Serono, Incyte, Janssen, Merck, Novartis, Pfizer, Roche, Thermo Fisher, Turning Point Therapeutics. P.K. Cheema: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Amgen, Hoffmann-La Roche, Bristol Myers Squibb, Beigene, Janssen, Bayer, EMD Serono, Merck, Novartis, Pfizer, Sanofi. All other authors have declared no conflicts of interest.