192P - Impact of oncogenic fibroblast growth factor receptor (FGFR) alterations in patients with advanced solid tumors in a real-world setting

Background

Selective FGFR inhibitors are approved for treatment (tx) of FGFR+ advanced urothelial cancer (UC) and cholangiocarcinoma (CCA). The prognostic FGFR+ impact in solid tumors shows mixed results for select solid tumor types (TT). This study assessed the real-world (RW) prognostic impact of FGFR+ on overall survival (OS) of patients (pts) in a tumor agnostic (TA) setting.

Methods

This retrospective study used the Flatiron/Foundation Medicine, Inc Clinico-genomic database (FMI), including data from ∼280 US cancer centers. Pts (age ≥18 y) had advanced/metastatic (adv/met) disease (except UC), evidence of FGFR testing, and started first-line (1L) systemic tx in the adv/met setting. All pts had FMI's tissue-based genomic profiling. Pts with prior selective FGFR inhibitor tx were excluded. FGFR+ was defined as ≥1 of 81 prespecified FGFR oncogenic mutations or any FGFR fusion involving an intact kinase domain. Pts with wildtype FGFR (FGFR-) were matched 3:1 with pts with FGFR+ on TT, age, sex, date of adv/met disease diagnosis, and FMI test version. The statistically powered primary objective assessed differences in TA RW OS from 1L tx initiation in pts with FGFR+ vs FGFR- adv/met disease treated with standard of care systemic tx. Secondary objectives assessed differences in tumor specific RW OS and in time to tx discontinuation or to next tx. Delayed entry models and covariate-adjusted stratified Cox models were used to mitigate bias.

Results

Data from 253 FGFR+ and 759 FGFR- pts were analyzed. Demographics, baseline disease and clinical characteristics were balanced between groups. There were no significant differences in TA RW OS from 1L between groups (HR, 0.97 [FGFR+ vs FGFR-]; p=0.78). Median RW OS from initiation of 1L tx was 1.13 y (95% CI, 0.92-1.52) and 1.01 y (95% CI, 0.89-1.15) for FGFR+ and FGFR- pts, respectively. There were no significant differences in RW OS between groups in tumor-specific comparisons, including CCA, breast cancer, and NSCLC.

Conclusions

There was no statistically significant difference in RW OS between pts with FGFR+ or FGFRadv/ met solid tumors, with a median OS of ∼1 year in both groups. These results highlight the poor prognosis and high unmet need for novel, targeted tx.

Clinical trial identification

Editorial acknowledgement

Frank Derosa, Parexel.

Legal entity responsible for the study

Janssen Research and Development.

Funding

Janssen Research and Development.

Disclosure

H. Sweiti: Financial Interests, Institutional, Stocks or ownership: Janssen R&D; Financial Interests, Institutional, Full or part-time Employment: Janssen R&D. L. Demirdjian: Financial Interests, Institutional, Full or part-time Employment: Janssen Research and Development; Financial Interests, Institutional, Stocks/Shares: Janssen Research and Development; Financial Interests, Institutional, Other, Patent: Janssen Research and Development; Non-Financial Interests, Project Lead: Janssen Research and Development. S. Triantos: Financial Interests, Institutional, Full or part-time Employment: Janssen R&D; Financial Interests, Institutional, Stocks or ownership: Janssen R&D. K. Standish: Financial Interests, Institutional, Full or part-time Employment: Johnson and Johnson, Merck; Financial Interests, Institutional, Stocks or ownership: Johnson and Johnson, Merck, Eli Lilly; Financial Interests, Institutional, Research Funding: Johnson and Johnson; Financial Interests, Institutional, Other, Patent: Johnson and Johnson. S. Thomas: Financial Interests, Institutional, Full or part-time Employment: Janssen R&D; Financial Interests, Institutional, Stocks or ownership: Janssen R&D. J. Greshock: Financial Interests, Institutional, Full or part-time Employment: Janssen R&D; Financial Interests, Institutional, Stocks or ownership: Johnson and Johnson. Q. Xia: Financial Interests, Institutional, Full or part-time Employment: Janssen R&D, Geron; Financial Interests, Institutional, Stocks or ownership: Janssen R&D, Geron; Financial Interests, Institutional, Other, Travel, accomodations, expenses: Janssen R&D, Geron. J. Paone: Financial Interests, Institutional, Full or part-time Employment: Aetion Inc. P. Sheridan: Financial Interests, Institutional, Full or part-time Employment: Aetion Inc. S. Pant: Financial Interests, Institutional, Advisory Role: Zymeworks, Ipsen, Novartis, Janssen; Financial Interests, Institutional, Research Funding: Mirati Therapeutics, Mirati Therapeutics, Lilly, Xencor, Novartis, Rgenix, Bristol Myers Squibb, Astellas Pharma, Purple Biotech, 4D Pharma, Boehringer Ingelheim, NGM Biopharmaceuticals, Janssen, Arcus Biosciences, Elicio Therapeutics. C. Massard: Financial Interests, Institutional, Speaker, Consultant, Advisor: Amgen, Astellas Pharma, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Celgene, Debiopharm Group, Genentech/Roche, Ipsen, Janssen R&D, Lilly, MSD, Novartis, Pfizer, Sanofi, Orion, Taiho Pharmaceutical, Blueprint Medicines, Innate Pharma, PharmaMar, Faron Pharmaceuticals. D.A. Reardon: Financial Interests, Institutional, Advisory Role: Merck, Novocure, Regeneron, Bristol Myers Squibb, Oncorus, Agenus, EMD Serono, Merck KGaA, Taiho Pharmaceuticals, Delmar Pharmaceuticals, Advantagene, Bayer, Imvax, Medicenna, Vivacitas Oncology, Anheart Therapeutics, Ellipses Pharma, Genenta Science, Kintara Therapeutics, Kiyatec, Agios; Financial Interests, Institutional, Research Funding: Celldex, Incyte, Agenus, EMD Serono, Acerta Pharma, Omniox, Enterome; Financial Interests, Institutional, Other, Honoraria: Merck, Novocure, Regeneron, Bristol Myers Squibb, Oncorus, Agenus, EMD Serono, Merck KGaA, Taiho Pharmaceutical, Advantagene, Bayer, DelMar Pharmaceuticals, Imvax, Medicenna, Sumitomo Dainippon Pharma, Vivacitas Oncology, Anheart Therapeutics, Deciphera, Ellipses Pharma, Genenta Science, Inovio Pharmaceuticals, Kintara Therapeutics, Kiyatec, Neuvogen, Taiho Pharmaceutical, Y-mAbs Therapeutics. Y. Loriot: Financial Interests, Personal, Advisory Board: Merck Kga, Pfizer, Gilead, Seattle Genetics, Tahio; Financial Interests, Personal, Other, lectures, advisory boards: MSD, AstraZeneca, Astellas, Janssen; Financial Interests, Personal, Other, lectures, advisroy boards: Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, Celsius; Financial Interests, Institutional, Steering Committee Member: Janssen; Financial Interests, Steering Committee Member: MSD, Astellas, Gilead/Immunomedics, Tahio; Financial Interests, Personal, Steering Committee Member: basilea; Financial Interests, Institutional, Local PI: Pfizer, MSD, Janssen, Exelexis, AstraZeneca, Pfizer, Merck Kga, BMS, Astellas, Gilead, Incyte; Financial Interests, Institutional, Coordinating PI: Janssen; Non-Financial Interests, Member: ESMO, ASCO, AACR; Non-Financial Interests, Other, scientific committee: ARC. M.H.H. Schuler: Financial Interests, Institutional, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Roche, Takeda, Amgen, GSK, Merck Serono, Sanofi, Janssen Oncology; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, AstraZeneca; Financial Interests, Institutional, Other, Honoraria: Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Amgen, Janssen-Cilag.