121P - Comprehensive cancer genome profiling as supportive tool for treatment decision-making in patients with metastatic solid tumors: Real-world evidence-based meta-analysis and nationwide cancer registry data implementation

Background

The surge in comprehensive cancer genome profiling (CGP) and advancements in next-generation sequencing (NGS) have reshaped precision oncology. However, their real-world impact and challenges in broader healthcare implementation remain underexplored and served as the aim of the present study.

Methods

We systematically searched Medline, Embase, and Web of Science for real-world evidence (RWE) studies on CGP and matched therapies in metastatic solid tumors. Pooled proportions of actionable genomic alterations, proportion of patients receiving a matched targeted therapy, treatment, and survival outcomes were calculated. Data from the Swedish cancer registries served as a case-study for a nationwide CGP implementation.

Results

From 7218 identified entries, 144 studies were included. In total 59.8% (95% Confidence Interval (CI): 55.0 – 64.4) of patients tested with CGP had actionable genomic alterations, with 15.6% (95% CI: 12.9-17.9%) receiving targeted therapy. The objective response rate among patients treated with targeted therapy was 23.9% (95% CI 20.8-27.3%). Meta-regression time projections analyses showed these rates will steadily increase towards 2030. Applying projections to Swedish biliary tract cancer patients (n = 383 in 2022), the number of patients identified with actionable mutations could rise from 66 to 83, with objective responses increasing from 18 to 30 by 2030. CGP-matched treatment correlated with prolonged progression-free survival (pooled Hazard Ratio (HR) = 0.63; 95% CI, 0.56-0.70; 18 studies) and overall survival (pooled HR = 0.60; 95% CI, 0.51-0.70; 21 studies) compared to conventional treatment among comparative studies.

Conclusions

Pooled analyses of RWE studies indicate that approximately one-fourth of the patients receiving GCP-matched treatment will experience an objective response. Furthermore, CGP-matched therapeutic decisions seemed to be correlated with improved outcomes. Our nationwide GCP cancer registry case-study, utilizing meta-regression projections, offers insights for future precision oncology strategies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

I. Zerdes: Non-Financial Interests, Leadership Role, Chair of the Young & Early-Career Investigators Steering Committee in the EORTC Breast Cancer Group: European Organisation for Research and Treatment of Cancer (EORTC). A. D'Alessio: Financial Interests, Personal, Other, AD received educational support for congress attendance and consultancy fees from Roche and AstraZeneca: Roche and AstraZeneca. T. Foukakis: Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Gilead Sciences; Financial Interests, Personal, Royalties, Authorship of two chapters in UpToDate: Wolters Kluwer; Financial Interests, Institutional, Coordinating PI, Clinical trial support (research grant and study drug): AstraZeneca; Financial Interests, Institutional, Coordinating PI, Clinical trial support (research grant and study drug): Novartis; Financial Interests, Institutional, Coordinating PI, Discount on the Prosigna PAM50 assay in ARIADNE clinical trial: Veracyte. G. Pentheroudakis: Financial Interests, Personal, Full or part-time Employment, Chief Medical Officer: ESMO; Non-Financial Interests, Member: ASCO, Hellenic Cooperative Oncology Group (HeCOG), Hellenic Society of Medical Oncology. A. Valachis: Financial Interests, Institutional, Research Grant, Research Grant for a research project on Molecular profiling of triple negative breast cancer: Roche; Financial Interests, Institutional, Coordinating PI, PRODAT trial: Novartis; Financial Interests, Institutional, Coordinating PI, CHECKMATE-401 trial: Bristol Myers Squibb; Financial Interests, Institutional, Coordinating PI, CHECKMATE-76K trial: Bristol Myers Squibb; Financial Interests, Institutional, Coordinating PI, TELEPIK trial: Novartis; Financial Interests, Institutional, Coordinating PI, DESTINY-Breast09 trial: AstraZeneca; Financial Interests, Institutional, Research Grant: MSD. All other authors have declared no conflicts of interest.