Introduction/Background Patients with metastatic gynaecological malignancies face several challenges, including limited treatment options and poor prognosis. Comprehensive molecular profiling for tumour-specific targeted treatments is investigated in the IMPRESS-Norway trial (NCT04817956), where patients receive experimental treatments tailored to the unique molecular profiles of their tumours as assessed by gene panel and whole genome sequencing. Herein we report on the genetic profiles and plausible therapeutic targets among gynaecological cancer patients screened for the IMPRESS-Norway trial.

Methodology The IMPRESS-Norway trial is a nationwide, prospective, non-randomised trial for all cancer patients with advanced-stage disease progressing on conventional standard-of care therapy. Targeted next-generation sequencing is employed using TSO500 (Illumina) to characterise tumour molecular profiles. A national tumour board evaluate the findings and provides advice on the choice of suitable targeted treatments. All enrolled patients are also offered diagnostic assessment through whole genome sequencing.

Results Between April 2021 and October 2023, genetic profiling was performed on 1,246 patients. Of those, 161 patients (13%) had gynaecological malignancies, with non-high-grade serous ovarian cancers (n=61, 38%), endometrial cancer (n=28, 17%) and cervical cancer (n=28, 17%) being the most prevalent subtypes. A total of 77 potentially actionable genetic alterations in 67 patients were identified, averaging at one alteration per patient (range 0–2). The most frequently observed targetable alterations were found in PIK3CA/PTEN, KRAS/NRAS, and ERBB2. Notably, 27% of the patients (43 in total) have started targeted treatments within the IMPRESS-Norway trial. Among all patients screened for IMPRESS-Norway, 19% were offered treatment. An additional 1% were referred to other ongoing clinical trials.

Conclusion The IMPRESS-NORWAY trial has thus far revealed prevalent and potentially clinically significant genetic alterations among the enrolled gynaecological cancer patients. Further investigation is needed to determine the representativeness of these findings for the patient group and to evaluate the efficacy of targeted treatments in gynaecological cancer therapy.

Disclosures Torkildsen reports honoraria or consultation fees from AstraZeneca, GSK and Pfizer. Lindemann reports grants/research support from GSK and advisory board fees from Astra Zeneca, Nycode, GSK and Eisai. Steinskog reports honoraria or consultation fees from Pfizer, Roche Norway and Bayer AS. Puco reports honoraria or consultation fees from Astellas Pharma, Astra Zeneca, Bayer, Bristol-Myers Squibb, Ipsen, Janssen-Cilaq, MSD and Pfizer AS. She has participated in company sponsored speakers bureau by Astellas Pharma, Astra Zeneca, Bayer, Bristol-Myers Squibb, Ibsen, Janssen-Cilaq, MSD and Pfizer AS and reports institutional support from Roche, Novartis, Eli Lilly, Astra Zeneca, InCyte, Merck and Illumina. Brabrand reports honoraria or consultation fees from Bayer and Pfizer. Flobak reports honoraria or consultation fees from Novartis, Pfizer, Pierre Fabre, Amgen and Bayer. Oppedal reports institutional support from Roche, Novartis, EliLilly, Astra Zeneca, InCyte, Merck and Illumina. Meltzer reports honoraria from GSK. Blix reports honoraria or consultation fees from AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Pierre Fabre and Roche. Russnes reports institutional honoraria from Illumina, Roche, Astra Zeneca, Bayer and Novartis. Bjørge reports research grant from AstraZeneca and participated in company sponsored speakers bureau by MSD and GSK. Helland reports research support from Roche, Novartis, Incyte, EliLilly, AstraZeneca, GSK, Ultimovacs and BMS.