Abstract 689P
Background
Osimertinib (osi) is the standard first-line treatment for patients with metastatic epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC). The patterns of disease progression and impact of local ablative therapy (LAT) on survival outcomes among patients receiving first-line (1L) osi warrants further studies.
Methods
This retrospective study enrolled patients (pts) with metastatic EGFRm NSCLC treated with 1L osi between June 2017 and June 2023. Survival data cut-off was performed in July 2024. Study endpoints included progression-free survival (PFS), time-to-treatment failure (TTF), overall survival (OS), pattern of disease progression (oligoprogression [OPD] versus systemic progression [SPD]) and impact of LAT on survival outcomes. OPD was defined as five or fewer metastases that were amenable to radical LAT, which included stereotactic body radiotherapy (SBRT), conventional radical radiotherapy and surgery.
Results
Of 291 pts enrolled, median age 64 (range 37 – 93), 187 (64%) female. 53 (18%) smokers, 230 (79%) had ECOG 0-1, and 153 (53%) had brain metastases. 137 (47%) had EGFR exon 19 deletion and 146 (50%) had EGFR exon 21 L858R mutation. Median follow up duration was 30 months (m) (95% CI 28 – 32). Median PFS, TTF and OS were 18m (95% CI 15 – 21), 22m (95% CI 19-25) and 34m (95% CI 29-39) respectively. 182 pts (63%) had disease progression at data cutoff, out of which, 68 (37%) and 114 (63%) had OPD and SPD respectively. Clinical characteristics were similar between pts with OPD and SPD. Pts with OPD experienced longer TTF and OS compared to those with SPD (TTF 26 vs 14m, p <0.001; OS 42 vs 25m, p <0.001). This remained significant after adjusting for gender, smoking status, ECOG, EGFR mutation, brain and liver metastases. Of the 68 pts with OPD, 31 received LAT (26 SBRT, 3 conventional radiotherapy and 2 surgery). There was a longer TTF trend among pts who received LAT compared to those without (34 vs 24m, p=0.095).
Conclusions
One-third of pts receiving 1L osi developed OPD upon disease progression. Pts with OPD exhibited longer TTF and OS compared to those with SPD. LAT to oligoprogression tends to further prolong TTF with osi.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
T.S.K. Mok: Financial Interests, Personal, Invited Speaker: ACEA Pharma, AbbVie, Alpha Biopharma, Amgen, Amoy Diagnostics, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Daz Group, Eli Lilly, Fishawack Facilitate, InMed Medical Communication, Janssen Pharmaceutical NV, Jiahui Holdings Co., LiangYiHui Healthcare, Lucence Health Inc., Lunit USA, Inc., MD Health, MSD, Medscape/WebMD, Merck Pharmaceuticals HK Ltd, Merck Serono, MiRXES, Novartis, OrigiMed Co. Ltd., PER, PeerVoice, Permanyer SL, Pfizer, Prime Oncology, Research to Practice, Roche, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co., Ltd., Shanghai Promedican Pharmaceuticals Co., Ltd, Taiho Pharmaceutical Co., Ltd, Takeda, Touch Medical Media; Financial Interests, Personal, Advisory Board: ACEA Pharma, AbbVie, Alpha Biopharma, Amgen, Amoy Diagnostics, Bayer Healthcare Pharmaceuticals Ltd., BeiGene, BerGenBio ASA, Berry Oncology, Berry Oncology, Blueprint Medicines, Boehringer Ingelheim, Bowtie Life Insurance Co Ltd, Bristol Myers Squibb, C4 Therapeutics, CStone Pharma, Cirina Ltd., Covidien LP, Curio Science, D3 Bio Ltd., Da Volterrra, Daiichi Sankyo, Eisai, Eli Lilly, F. Hoffmann-La Roche Ltd / Genentech, Fishawack Facilitate, G1 Therapeutics, Gilead Sciences, Gritstone Oncology, Guardant Health, Hengrui, IQVIA, Ignyta, Imagene AI Ltd, Incyte Corporation, Inivata, Janssen, Lakeshore Biotech, Loxo Oncology, Lucence Health Inc., Lunit USA, Inc., MSD, Medscape LLC / WebMD, Merck Serono, MiRXES, Mirati Therapeutics, MoreHealth, Novartis, OSE Immunotherapeutics, OrigiMed, Pfizer, Prenetics Global Limited, Puma Tech., Qiming Dev., Regeneron Pharmaceuticals Inc., Roche, SFJ Pharmaceutical Ltd., Sanofi-Aventis, Simcere Zaiming, Inc, Simcere of America Inc, Synergy Research, Takeda, Tigermed, Vertex Pharmaceuticals, Virtus Medical, Yuhan Corporation; Financial Interests, Personal, Other, consultation services: AVEO Pharmaceuticals, Inc, Alentis Therapeutics AG, BerGenBio ASA, Bridge Biotherapeutics Inc, Elevation Oncology, GLG’s Healthcare, Genentech, Illumina, Inc., Novocure GmbH, Phanes Therapeutics, geneDecode Co., Ltd; Financial Interests, Personal, Other, Consultation services: Adagene, XENCOR, Inc; Financial Interests, Personal, Other, Consultation Services: HiberCell, Inc., Seagen International GmbH, AnHeart Therapeutics Inc, Ningbo NewBay Technology Development Co., Ltd., InxMed (Hong Kong) Limited; Financial Interests, Personal, Other, Consultant Services: Schrödinger, Inc; Financial Interests, Personal, Member of Board of Directors: AstraZeneca, Aurora, Insighta; Financial Interests, Personal, Member of Board of Directors, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Personal, Stocks/Shares, Former known as Hutchison Chi-Med: HutchMed; Financial Interests, Personal, Stocks/Shares: Biolidics Ltd., Aurora Tele-Oncology, AstraZeneca, D3 Bio, Lunit Inc., Precentics, Alentis Therapeutics AG; Financial Interests, Institutional, Funding, For clinical trials performed at CUHK: AstraZeneca, BMS, Merck Serono, MSD, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery, Takeda, G1 Therapeutics, Clovis Oncology; Non-Financial Interests, Personal, Advisory Role: geneDecode; Non-Financial Interests, Personal, Other, Invited Speaker: AstraZeneca, Aurora Tele-Oncology, Lunit USA, Inc.; Non-Financial Interests, Personal, Leadership Role, Term ended: Chinese Society of Clinical Oncology (CSCO); Non-Financial Interests, Personal, Leadership Role, Term ended on 30 June 2022: American Society of Clinical Oncology (ASCO); Non-Financial Interests, Personal, 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, Personal, Leadership Role, Term ended on 30 April 2019: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Personal, Leadership Role, Honorary Secretary, from Dec 2022 - Present: Hong Kong Academy of Sciences. S.C.M. Li: Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Amgen, Pfizer, Takeda, ACE Oncology, Gilead, Guardant Health, Janssen, Merck, MSD, BMS, Daiichi Sankyo, AnHeart Therapeutics, Yuhan, Blossomhill Therapeutics. All other authors have declared no conflicts of interest.