Abstract 1325P
Background
The POSEIDON phase 3 trial showed an improvement in overall survival (OS) with T+D+CT vs CT in 1L mNSCLC. A post-hoc analysis showed a trend for sustained OS benefit with T+D+CT vs CT in patients with STK11, KEAP1 or KRAS mutations. These patients may require novel combinations (eg. incl. CTLA4) that might enhance responses to PD(L)-1 inhibitor-based regimens.
Methods
POSEIDON’s clinical and laboratory data in the T+D+CT and D+CT arms were combined with radiomic data from computed tomography scans via a segmentation algorithm to generate the T_full set and with available genomic data for NSq cases, to generate the T_NSq set. ML was used to train models to identify patients predicted to derive higher OS benefit from addition of T to D+CT. Nested cross-validation was used to assess performance.
Results
Comparison of OS for T+D+CT vs D+CT within the T_full set yielded a HR of 0.88 (95% CI: 0.73-1.05). A model based on clinical+radiomics data yielded an improved HR of 0.75 (95% CI: 0.58-0.98) for patients with scores >median. Neutrophil/Lymphocyte ratio, radiomics and albumin contributed most to the predictive power. Within the T_NSq set, a model based on clinical+genomic data yielded a HR of 0.56 (95% CI: 0.33-0.97) for patients with scores >median, as compared to 0.88 (95% CI: 0.68-1.12) in the total T_NSq set. EGFR (non activating), FGFR3, CDKN2A, KRAS, STK11 mutations contributed most to the predictive power. Table: 1325P
| Data set description and baseline characteristics | Dataset | Analysis set | N | Age, median (range) | Sex n (%) | Histology n (%) | PD-L1 status n (%) |
| POSEIDON | P_full | ITT | 676 | 64.0 (27-87) | M: 522 (77.2)F: 54 (22.8) | NSq: 423 (62.6)Sq: 252 (37.3)Other: 1 (0.1) | ConclusionsThe ML multimodal models yielded signatures identifying patients that would benefit from T addition to D+CT in 1L mNSCLC: NSq histology and an EGFRwt, FGFR3wt, CDKN2Awt and KRAS and STK11 mutation signature drive higher benefit. Limitations of this analysis include its post hoc nature and need for external validation (planned). TRITON (NCT06008093) study is further evaluating STK11/KEAP1/KRASm mNSCLC population with T+D+CT vs pembrolizumab+CT. Clinical trial identificationEditorial acknowledgementLegal entity responsible for the studyAstraZeneca. FundingAstraZeneca. DisclosureF. Skoulidis: Financial Interests, Personal, Invited Speaker: ESMO, AACR, IASLC, Japanese Lung Cancer Society, Medscape LLC, Intellisphere LLC, VSPO McGill Université de Montreal, MJH Life Sciences, IDEOlogy Health, MI&T, PER LLC, CURIO LLC, DAVA Oncology, BMS and RV Mais Promocao Eventos LTDS; Financial Interests, Institutional, Research Grant: Amgen, Revolution Medicines, Mirati Therapeutics, Boehringer Ingelheim, Merck & Co, and Novartis; Financial Interests, Institutional, Research Grant, Spouse: Almmune, Genentech; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen Inc., Revolution Medicines, Novartis, BridgeBio, BeiGene, BergenBio, AstraZeneca, Guardant Health Inc., Calithera Biosciences, Tango Therapeutics, Merck Sharp & Dohme, Roche, Novocure, Hookipa Pharma; Financial Interests, Institutional, Speaker, Consultant, Advisor, Spouse: Genentech, Novartis; Financial Interests, Personal, Stocks or ownership: BioNTech SE, Moderna Inc.; Financial Interests, Institutional, Trial Chair: Pfizer. S. Jabbour: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck; Financial Interests, Personal, Expert Testimony: Dechert LLP; Financial Interests, Institutional, Funding: Merck, Adlai, BeiGene, Guardant; Non-Financial Interests, Institutional, Local PI: Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: Ideology, BeiGene, MJH LifeScience, Binaytara. E.B. Garon: Financial Interests, Institutional, Advisory Role: AbbVie; ABL-Bio; AstraZeneca, Boehringer-Ingelheim; Bristol Myers Squibb; Dracen Pharmaceuticals; EMD Serono; Eisai; Eli Lilly; Gilead, GSK; Merck; Natera; Novartis; Personalis; Regeneron; Sanofi; Shionogi; Xilio; Zymeworks; Financial Interests, Institutional, Research Grant: ABL-Bio; AstraZeneca; Bristol Myers Squibb; Daiichi Sanko; Dynavax Technologies; Eli Lilly; EMD Serono; Genentech; Gilead; Iovance Biotherapeutics, Merck; Mirati Therapeutics; Neon; and Novartis. P. Iyengar: Financial Interests, Personal, Advisory Board: AstraZeneca, Novocure, BioConvergent; Financial Interests, Institutional, Funding: Incyte. G. Scagliotti: Financial Interests, Personal, Speaker, Consultant, Advisor, Independent Consultant: AstraZeneca. L. Ferrer, G. Etchepare, O. Gallinato, T. Colin, P. Menu: Financial Interests, Personal, Full or part-time Employment: Sophia Genetics; Financial Interests, Personal, Stocks/Shares: Sophia Genetics. J. Faure, P. Bernard: Financial Interests, Personal, Full or part-time Employment: Sophia Genetics. Y. Lin: Financial Interests, Personal, Full or part-time Employment: Novartis. L. Cai, J. Faria D. Dellamonica, Y. Zhang: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Remorino, K.P. Miller: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. L. Luciani-Silverman: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca, BMS. Resources from the same session1291P - Real-world treatment and overall survival (OS) in patients (pts) with ROS1-positive (ROS1+) non-small cell lung cancer (NSCLC) in England between 2014 and 2023Presenter: Alastair Greystoke Session: Poster session 05 1292P - A national real-world analysis of ROS1+ metastatic non-small cell lung cancer patients management (explore ALK, cohort 2, GFPC 03-2019)Presenter: Gaelle Rousseau Bussac Session: Poster session 05 1293P - Mechanisms of resistance to selpercatinib in RET activated NSCLC and MTC from the LIBRETTO-001 trialPresenter: Ben Solomon Session: Poster session 05 1294P - Non-adenocarcinoma histology in patients with RET+ lung cancer: Response to RET-inhibitors and survival from the RET-MAP registryPresenter: Arianna Marinello Session: Poster session 05 1295P - EP0031 a next-generation selective RET inhibitor (SRI): Correlation of molecular and clinical responses in patients with RET alteration positive solid tumours naïve to or following prior SRIPresenter: Elena Garralda Session: Poster session 05 1296P - A phase II study to evaluate the efficacy and safety of BB-1701 in advanced or metastatic NSCLC patients with HER2 mutation/amplificationPresenter: Caicun Zhou Session: Poster session 05 1297P - A phase II study of pyrotinib combined with apatinib in first-line treatment of advanced non-small cell lung cancer patients with primary HER-2 mutations/amplificationPresenter: Wenxin Jiang Session: Poster session 05 1299P - First-line immunotherapy versus BRAF and MEK inhibitors for patients with BRAF V600E mutant metastatic non-small cell lung cancerPresenter: Alessandro Di Federico Session: Poster session 05 1300P - Treatment sequences in BRAF-V600-mutant non-small cell lung cancer: First-line targeted therapy versus first-line (chemo-) immunotherapyPresenter: Marcel Wiesweg Session: Poster session 05 This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
|