185P - Real-world data analysis of genomic profiling-matched targeted therapy outcomes in patients with fusion-positive NSCLC

Background

While clinical oncology societies such as ESMO have recommended the use of Comprehensive Genomic Profiling (CGP) to identify patients eligible for targeted treatment, full utilization of the potential benefits of CGP has not yet occurred in routine clinical practice. Here we assess the compliance to ESMO targeted therapy recommendations and associated outcomes for CGP-based ALK, RET, ROS1, and NTRK fusions detected in a large real-world, observational dataset of advanced NSCLC patients.

Methods

We retrospectively analyzed de-identified stage IV or metastatic NSCLC records from the Tempus database which encompasses molecular and clinical data from hundreds of clinics across the United States sequenced with the Tempus xT assay (DNA and whole-exome capture RNA NGS) from 2018-2022. Therapeutic adoption was analyzed in cases with ≥30 days of medication data post-sequencing. Real-world overall survival (rwOS) was defined as the interval from start of medication prescribed after sequencing to date of death, censored on the last known physician encounter. A cox proportional hazards model was fit to evaluate the relationship between matched targeted therapy compliance and rwOS in fusion-positive patients.

Results

Among 1,950 patients that met study inclusion criteria, N= 65 (3.3%) had a fusion detected by CGP (N=38 ALK fusions, N=15 RET fusions, N=11 ROS1 fusions and N= 1 NTRK fusion). The overall compliance rate of targeted therapy was 82% (N=53). The median time from sequencing to start of targeted therapy was < 1 month. Fusion-positive patients receiving matched therapy had significantly longer rwOS than those that did not receive matched therapy (HR=0.13, p<0.001). ALK-positive patients receiving matched therapy had significantly longer rwOS than those that did not receive matched therapy, (HR=0.12, p<0.05).

Conclusions

This study demonstrates that in a real-world, retrospective cohort, most oncologists utilized CGP to timely treat patients with ESMO-recommended targeted therapy for fusion-positive advanced NSCLC. More importantly, CGP-matched guideline-recommended treatment is associated with improved rwOS. Future studies are needed to understand the gap in compliance with matched targeted therapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Tempus Labs.

Disclosure

J. Patel: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda. R. Ben-Shachar: Financial Interests, Personal, Full or part-time Employment: Tempus Labs; Financial Interests, Personal, Stocks/Shares: Tempus Labs, Myriad Genetics. K. Nadhamuni: Financial Interests, Institutional, Full or part-time Employment: Tempus Labs; Financial Interests, Institutional, Stocks/Shares: Tempus Labs; Financial Interests, Institutional, Other, Full time employee: Tempus Labs. M. Carty: Financial Interests, Institutional, Full or part-time Employment: Tempus Labs; Financial Interests, Institutional, Stocks/Shares: Tempus Labs; Financial Interests, Institutional, Advisory Board: Tempus Labs. R. Pelossof: Financial Interests, Personal, Full or part-time Employment: Tempus; Financial Interests, Personal, Other, RSUs: Tempus. I. Klein: Financial Interests, Institutional, Full or part-time Employment, Full time employee, also granted shares in the company with potential future value: Tempus Labs, Inc.; Financial Interests, Institutional, Stocks/Shares, Granted as part of overall compensation, may have future value.: Tempus Labs, Inc.; Non-Financial Interests, Member of Board of Directors, This is a not for profit organization (503c) that advocates for appropriate medication oversight and usage in the US healthcare system, based on literature regarding waste and medical error in today's system: Get the Meds Right. H. Nimeiri: Financial Interests, Personal, Full or part-time Employment: Tempus; Financial Interests, Personal, Stocks/Shares: Tempus, AbbVie. C. Aggarwal: Financial Interests, Personal, Advisory Board: AstraZeneca, Celgene, Genentech, Lilly, Merck, Bluprint, Daiichi/Sankyo, Sanofi, Eisai, BeiGene, Shionogi, Turning Point, Pfizer, Janssen, Boehringer Ingelheim. R.D. Gentzler: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, Gilead, Janssen, Mirati, Daiichi Sankyo, Sanofi, Oncocyte, Jazz Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Clinical Care Options, OncLive, Targeted Oncology, Society for Immunotherapy of Cancer (SITC); Financial Interests, Institutional, Local PI: Janssen, Mirati, Daiichi Sankyo, Bristol Myers Squibb, AstraZeneca, Jounce Therapeutics, Takeda, Bristol Myers Squibb, Merck, Chugai, Amgen; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Coordinating PI: Mirati; Non-Financial Interests, Leadership Role: Hoosier Cancer Research Network; Non-Financial Interests, Principal Investigator: NCI ETCTN; Non-Financial Interests, Personal, Other, Travel support for attending meetings for invited speaker: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Other, Member of Lung Cancer Scientific Review Committee: American Society of Clinical Oncology, Scientific Review Committee; Non-Financial Interests, Other, Committee Member: NCI Investigational Drug Steering Committee; Non-Financial Interests, Officer, Associate Editor: Journal of Thoracic Oncology, ASCO Meeting Abstracts.