2317P - Mutational landscape and therapeutic implications in squamous cell carcinomas

Background

Disseminated squamous cell carcinomas (SCCs) are traditionally considered void of actionable molecular targets, in contrast to adenocarcinomas, where an increasing number of targets are identified. SCC rarely undergo routine molecular testing and approved targeted therapies are rare in this population. Access to extensive molecular profiling and subsequent matching with experimental therapies may improve the outlook for patients (pts) with SCC. We report the mutational landscape in SCC and subsequent therapeutic implications.

Methods

Pts with late-stage SCCs (oesophageal cancer, cervical cancer, head and neck cancer, non-small-cell lung cancer, skin cancer, thymic carcinoma, or unknown primary tumor) referred to a phase I facility were included in a prospective, single-center, single-arm open-label genomic profiling study (NCT02290522). Fresh tumor tissue was obtained for whole exome sequencing or whole genome sequencing, RNA sequencing and chromosomal aberration analysis. Circulating tumor DNA was obtained when fresh biopsy was not possible. Each individual genomic report was reviewed and discussed by a multidisciplinary molecular tumor board dedicated to precision medicine. When possible, pts were treated with regimens matched to the genomic profile.

Results

Between November 2013 and March 2023, a total of 189 pts with SCC were enrolled. Genomic profiles were obtained in 160 (85%). At least one actionable target was detected in 77 (48%) with a total of 117 actionable alterations including DNA damage repair response pathway (N=42, 36%), expression profiles matched to monoclonal antibodies (N=21, 18%), and high tumor mutational burden. (N= 15, 13%). In total, 18 pts (23%) were treated with regimens matched to the genomic profile. However, since 2021, 37% (7/19) of the pts with actionable targets have been treated with targeted treatment. Among the evaluable pts (N=6), one had complete response, two had partial response, and three had stable disease.

Conclusions

This study illustrates increasing targeted treatment options for SCCs, thereby emphasizing the importance of genomic profiling.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Eriksen: Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Other, Travel/Accommodation: Servier, MSD. M. Hoejgaard: Financial Interests, Personal, Other, Advisory role for various diagnostic companies/investors: LingoMedical; Financial Interests, Personal, Stocks/Shares, Stocks, I. Spanggaard: Financial Interests, Institutional, Local PI: Roche, Puma Biotechnology, MSD, Genentech, Incyte, AstraZeneca, Orion, Pfizer; Non-Financial Interests, Principal Investigator: Roche, Puma Biotechnology, MSD, Genentech, Incyte, AstraZeneca, Orion, Pfizer. K.G. Daugaard: Financial Interests, Personal, Advisory Board, Prostate Cancer: Janssen; Financial Interests, Personal, Advisory Board, Prostate Cancer: Astellas, Bayer, MSD; Financial Interests, Personal, Advisory Board, Anticoagulation therapy: BMS; Financial Interests, Personal, Advisory Board: AA; Financial Interests, Institutional, Coordinating PI: BMS, Roche, MSD. U.N. Lassen: Financial Interests, Personal, Advisory Board: Bayer, Novartis; Financial Interests, Institutional, Research Grant: Roche, BMS, Pfizer, GSK, Lilly, Incyte. K.S. Rohrberg: Financial Interests, Personal, Invited Speaker: Bayer, Amgen, MSD, GSK; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Institutional, Coordinating PI, Compensation for conduction of clinical trial: Lilly, Roche/Genentech, Bristol Myers Squibb, Symphogen, Pfizer, Novartis, Alligator Bioscience, Genmab, BioInvent, Monta Bioscience; Financial Interests, Institutional, Other, Compensation for conduction of clinical trial: Bayer, Incyte, Puma Biotechnology, Orion Clinical. All other authors have declared no conflicts of interest.