Abstract 1270P
Background
Bone metastases (BMs) occur in 20-40% of metastatic NSCLC. BMs adversely affect patient (pt) quality of life and are associated with increased mortality, but have not been typically used as stratification factor for clinical trials. Our aim was to evaluate genomic alterations associated with BMs at diagnosis in NSCLC and their impact on survival outcomes.
Methods
The AACR GENIE Biopharma Collaborative (BPC) is a registry of clinical and genomic data from patients with NSCLC who had tumor sequencing (55-500 genes) from 2015-2017 at four academic centers. Imaging reports and medical oncologists’ clinical notes were retrospectively curated using the PRISSMM framework. Kaplan–Meier (KM) method was used to estimate the median overall survival (OS). Hazard ratio (HR) and 95% confidence intervals (95% CI) were calculated using the Cox Proportional-Hazards Model with survival endpoints adjusted for left truncation introduced by the study inclusion criteria. Association between variables and BMs were analyzed using Mann-Whitney U and Fisher’s exact test.
Results
There were 722 pts with Stage IV NSCLC in the BPC cohort, including 297 (41.1%) with BMs at diagnosis. Median OS from diagnosis was worse in pts with BMs vs without BMs (median 12.5 vs 18.2 months (m), HR 1.31; 95% CI 1.09-1.56). BMs at diagnosis was associated with worse OS in multivariate analysis after adjusting for age, sex, smoking, histology, and site of distant metastasis including brain and liver metastasis (HR 1.37; 95% CI 1.13-1.65). EGFR mut was associated with BMs vs no BMs (35% vs 23%, p<0.001). Ex19del (p=0.01) but not L858R (p=0.29) was associated with BMs. Median OS for EGFR mut pts with BMs was 25.4 vs 32.2 m in those without BMs (HR 1.42, 95% CI 0.99-2.03). OS from diagnosis was significantly worse in pts with BMs who had KRAS mut (median 5.2 vs 12.0 m, p<0.01) or concurrent EGFR mut/TP53 mut (median 22.2 vs 29.6 m, p=0.045) vs no BMs with these mutations.
Conclusions
BMs at diagnosis in stage IV NSCLC are associated with EGFR mut, specifically EGFR ex19del, and worse survival despite adjusting for other known prognostic factors. BMs should be considered as a stratification factor for clinical trials in advanced NSCLC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
American Association of Cancer Research (AACR). AACR Project GENIE receives funding from Amgen, Inc.; Bristol Myers Squibb Company; Merck Sharp & Dohme Corp.; AstraZeneca UK Limited; Genentech; Novartis; Pfizer, Inc.; Bayer Healthcare Pharmaceuticals, Inc.; Boehringer Ingelheim; Janssen Pharmaceuticals Inc.
Disclosure
G.J. Riely: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Infinity Pharmaceutical; Financial Interests, Institutional, Research Grant: Mirati Therapeutics; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme. J.A. Lavery: Financial Interests, Personal, Research Grant: AACR. J.L. Warner: Financial Interests, Personal, Member of the Board of Directors, Deputy Editor: HemOnc.org LLC; Financial Interests, Personal, Stocks/Shares: HemOnc.org LLC; Financial Interests, Personal, Advisory Role: IBM Watson Oncology; Financial Interests, Personal, Advisory Role: Westat; Financial Interests, Personal and Institutional, Research Grant: NIH; Financial Interests, Personal and Institutional, Research Grant: AACR. M.L. LeNoue-Newton: Financial Interests, Personal and Institutional, Research Grant: AACR GENIE Project; Financial Interests, Personal and Institutional, Research Grant: GE Healthcare. S.M. Sweeney: Financial Interests, Personal and Institutional, Research Grant: Amgen; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Genentech; Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Research Grant: Janssen; Financial Interests, Personal and Institutional, Research Grant: Merck; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal and Institutional, Research Grant: Analysis Group. B. Samantha: Financial Interests, Personal and Institutional, Research Grant: AACR. A. Sacher: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Genentech-Roche; Financial Interests, Personal, Advisory Board: KisoJi; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Tesaro; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Amgen; Financial Interests, Personal and Institutional, Research Grant: Merck; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Research Grant: Genentech-Roche; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: Spectrum; Financial Interests, Personal and Institutional, Research Grant: GSK. K.L. Kehl: Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Institutional, Other, Honoraria: IBM; Financial Interests, Personal, Advisory Role: Aetion. N. Leighl: Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Array; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: Guardant; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: CADTH; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Sanofi Genzyme; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Teva-Oncotest. D. Schrag: Financial Interests, Personal and Institutional, Invited Speaker: Pfizer; Financial Interests, Personal and Institutional, Invited Speaker: Jama; Financial Interests, Institutional, Research Grant: AACR. P. Bedard: Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Institutional, Advisory Role: BMS; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Servier; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: PTC Therapeutic; Financial Interests, Institutional, Research Grant: Nektar; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Mersana; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Bicara. All other authors have declared no conflicts of interest.