1349P - Continuing osimertinib in combination with chemotherapy after osimertinib failure reduces CNS progression in patients with EGFR-mutated NSCLC and CNS metastases

Background

Central nervous system (CNS) metastases are common among patients with epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC). Chemotherapy (ChT) is the standard treatment for patients with metastatic EGFRm NSCLC patients failing osimertinib but has limited CNS activity. The role of continuing osimertinib concurrently with ChT after osimertinib failure for CNS control is uncertain.

Methods

This retrospective study included patients with metastatic EGFRm NSCLC who progressed on osimertinib and received ChT from 01/11/2017 to 17/03/2023. Primary endpoint is comparison of time to CNS progression between patients treated with osimertinib plus ChT versus ChT alone after progression on osimertinib. Time to CNS progression was defined from the starting date of ChT to radiological progression of CNS metastases. Hazard ratios and 95% confidence interval were estimated by Cox regression.

Results

A total of 180 patients were analyzed. Median age was 62 (34-80). 28 (16%) received osimertinib as first-line treatment. 33 patients continued osimertinib with ChT (OSIM+) and 147 patients received ChT alone (OSIM-). Prior to starting ChT, 30/33 (91%) and 52/147 (35%) patients had known CNS involvement, among which 8 and 27 had received prior whole brain radiotherapy (WBRT), in the OSIM+ versus OSIM- arms respectively. In the total population, osimertinib plus ChT did not reduce risk of CNS progression. In patients with known CNS metastases, osimertinib plus ChT significantly reduced CNS progression. Numerically fewer patients in the OSIM+ arm received salvage WBRT. Table: 1349P

*CNS/systemic progression or death PFS, progression free survival

Conclusions

Continuing osimertinib concurrently with ChT after osimertinib failure may reduce CNS progression in patients with known CNS metastasis, and the risk of being subjected to WBRT. Future prospective study is warranted to address this issue.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Li: Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Amgen, Pfizer, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Takeda; Financial Interests, Personal, Research Grant: Gilead. K.W.C. Lee: Financial Interests, Personal, Full or part-time Employment: ACT Genomics; Financial Interests, Personal, Stocks/Shares: ACT Genomics; Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen, Boehringer Ingelheim, CStone Pharmaceuticals, GSK, Merck, Merck Sharp and Dohme, Novartis, Pfizer, Roche; Financial Interests, Personal, Advisory Board: Janssen. H.H.F. Loong: Financial Interests, Personal, Invited Speaker: Bayer, Eli Lilly, Guardant Health, Illumina, MSD; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Novartis, Takeda. T.SK. Mok: Financial Interests, Personal, Invited Speaker: AbbVie, Acea Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Daiichi Sankyo, Fishawack Facilitate, InMed Medical Communication, Lunit USA, Inc., Merck Serono, MSD, Roche, MD Health, Medscape/WebMD, PeerVoice, Touch Medical Media, Permanyer SL, Prime Oncology, Research to Practice, Sanofi-Aventis, Takeda, Per, Daz Group, Lucence Health Inc., Janssen Pharmaceutical NV, Jiahui Holdings Co., LiangYiHui Healthcare, Merck Pharmaceuticals HK Ltd, MiRXES, Novartis, OrigiMed Co. Ltd., Pfizer, Shanghai BeBirds Translation & Consulting Co., Ltd., Taiho Pharmaceutical Co., Ltd; Financial Interests, Personal, Advisory Board: AbbVie, Acea Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Blueprint Medicines, Berry Oncology, CStone Pharma, Daiichi Sankyo, Fishawack Facilitate, Eisai, Gritstone Oncology, Guardant Health, G1 Therapeutics, Hengrui, Ignyta, IQVIA, Incyte Corporation, Inivata, Janssen, Loxo Oncology, Qiming Dev., Lunit USA, Inc., Merck Serono, MSD, Roche, Mirati Therapeutics, MoreHealth, Novartis, OrigiMed, Puma Tech., Sanofi-Aventis, Takeda, Virtus Medical, Yuhan, Curio Science, Bayer Healthcare Pharmaceuticals Ltd., Covidien LP, C4 Therapeutics, Cirina Ltd., Lucence Health Inc., Da Volterrra, F. Hoffmann-La Roche Ltd / Genentech, Gilead Sciences, Medscape LLC / WebMD, MiRXES, Ose Immunotherapeutics, Pfizer, SFJ Pharmaceutical Ltd., Synergy Research, Tigermed, Vertex Pharmaceuticals, Berry Oncology, D3 Bio Ltd., Lakeshore Biotech; Financial Interests, Personal, Member of Board of Directors: AstraZeneca; Financial Interests, Personal, Member of Board of Directors, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Personal, Officer, Chairman: ACT Genomics-Sanomics Group; Financial Interests, Personal, Stocks/Shares: Sanomics Ltd., Biolidics Ltd., Aurora Tele-Oncology, AstraZeneca; Financial Interests, Personal, Stocks/Shares, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: Merck Serono, AstraZeneca, BMS, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology; Non-Financial Interests, Advisory Role: geneDecode; Non-Financial Interests, Other, Invited Speaker: AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc., Sanomics Ltd.; Non-Financial Interests, Leadership Role, Term ended on 30 June 2022: American Society of Clinical Oncology (ASCO); Non-Financial Interests, Leadership Role: Asian Thoracic Oncology Research Group (ATORG), Chinese Lung Cancer Research Foundation Limited (CLCRF), Hong Kong Cancer Fund (HKCF), Hong Kong Cancer Therapy Society (HKCTS), St. Stephen’s College & Prep. School (Hong Kong); Non-Financial Interests, Leadership Role, Term ended: Chinese Society of Clinical Oncology (CSCO); Non-Financial Interests, Leadership Role, Term ended on 30 April 2019: International Association for the Study of Lung Cancer (IASLC). All other authors have declared no conflicts of interest.