Abstract 565P
Background
Acquired genomic alternations are known mechanisms of resistance to osimertinib in patients with advanced epidermal growth factor receptor (EGFR) positive non-small cell lung cancer (NSCLC). Addition of genome-guided targeted therapy (GGTT) to osimertinib may improve treatment outcomes.
Methods
This retrospective study reviewed 226 metastatic EGFR mutation positive NSCLC patients who received systemic therapy after failing osimertinib. Primary endpoints include time-to-treatment failure (TTF) and overall survival (OS) from post-osimertinib failure.
Results
Total of 68 patients had genomic analysis for osimertinib resistance and 21 (30%) had targetable genomic alternations. Out of which, 17 received osimertinib plus GGTT (13 MET amplification, 2 ALK rearrangement, 1 RET rearrangement and 1 BRAF V600E mutation) and 209 patients received chemotherapy. Median follow-up were 10.0 and 30.1 months for GGTT and chemotherapy group respectively. The GGTT group achieved significantly longer TTF (not reached [NR] vs 5.1 months, HR 0.19, 95% CI 0.08-0.48, p<0.001) and OS (NR versus 10.5 months, HR 0.27, 95% CI 0.09-0.86, p=0.026) compared to those receiving chemotherapy. These results remained significant after multivariate analysis (Table). In subgroup analysis, TTF of GGTT group was superior to chemotherapy alone (n=148) (NR versus 4.5 months, HR 0.18, p<0.001), chemotherapy plus osimertinib (n=41) (NR versus 6.2 months, HR 0.23, p=0.003) and chemotherapy plus anti-PD(L)1 plus anti-VEGF (n=20) (NR versus 6.3 months, HR 0.25, p=0.009), respectively. Table: 565P
Time to treatment failure | Overall survival | |||||||
Univariate | Multivariate | Univariate | Multivariate | |||||
HR | P-value | HR | P-value | HR | P-value | HR | P-value | |
Age (>65) | 0.95 | 0.74 | 1.16 | 0.35 | ||||
Gender (Female) | 0.94 | 0.43 | 0.85 | 0.046 | ||||
PS (>1) | 1.67 | 0.014 | 1.75 | 0.009 | 2.54 | <0.001 | 2.73 | <0.001 |
EGFR (ex19 del vs L858R)* | 1.03 | 0.83 | 0.98 | 0.91 | ||||
Line of Osimertinib (>1) | 1.51 | 0.037 | 1.40 | 0.10 | ||||
CNS metastases | 1.09 | 0.55 | 1.28 | 0.12 | ||||
Liver metastases | 1.30 | 0.05 | 1.36 | 0.05 | 1.42 | 0.037 | 1.50 | 0.016 |
Bone metastases | 1.92 | 0.001 | 1.71 | 0.011 | ||||
Therapy (GGTT) | 0.19 | <0.001 | 0.22 | 0.001 | 0.27 | 0.026 | 0.24 | 0.015 |
∗2 patients with EGFR mutations other than exon 19 deletion and exon 21 L858R mutation excluded from analysisCNS, central nervous system; EGFR, epidermal growth factor receptor; PS, performance status
Conclusions
The combination of GGTT and osimertinib improves TTF and OS in EGFR mutation positive NSCLC patients failing osimertinib. Future prospective comparative study is warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M.S.C. Li: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Takeda, Pfizer, Guardant Health; Financial Interests, Personal, Research Grant: Gilead, Takeda; Financial Interests, Personal, Invited Speaker: BMS, Amgen, ACE Oncology, AstraZeneca, Novartis, Takeda. K.W.C. Lee: Financial Interests, Personal, Full or part-time Employment: ACT Genomics; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Takeda, Janssen, C-stone; Financial Interests, Personal, Advisory Board: Merck, Janssen, Novartis; Financial Interests, Personal, Stocks or ownership: ACT Genomics, Prenetics. H.H.F. Loong: Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, MSD; Financial Interests, Personal, Invited Speaker: Eli Lilly, Illumina, Bayer, Guardant Health; Financial Interests, Personal, Advisory Board: Novartis, Takeda. T.S.K. Mok: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Berry Oncology, Boehringer Ingelheim, C4 Therapeutics, D3 Bio, Eisai, G1 Therapeutics, Gritstone Oncology, GeneDecode, Hutchmed, Incyte Corporation, IQVIA, Lilly, Lunit, MSD, Novartis, Puma Biotechnology, Roche, SFJ Pharmaceuticals, Vertex Pharmaceuticals, Yuhan Corporation, ACEA Pharma, AstraZeneca, Blueprint, BMS, Covidien LP, Curio Science, Daiichi Sankyo, Fishawack Facilitate, Gilead Sciences, Guardant Health, Hengrui, Ignyta, Inivata, Janssen, Loxo Oncology, Merck Serono, Mirati, Origimed, Pfizer, Sanofi Aventis, Takeda, Virtus; Financial Interests, Personal, Research Grant: AstraZeneca, BMS, Pfizer, Roche, Novartis, SFJ Pharmaceuticals, MSD, G1 Therapeutics, Takeda, XCovery, Merck Serono; Financial Interests, Personal, Invited Speaker: ACEA Pharmaceuticals, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Fishawack Facilitate, Janssen, Lucence Health, Medscape LLC, MSD, OrigiMed, PeerVoice, Pfizer, Research to Practice, Sanofi-Aventis, Liangyihui Network Technology, Takeda, Alpha Biopharma, Amoy Diagnostics, BeiGene, BMS, Daz Group, InMed Medical Communication, Lilly, MD Health Brazil, Merck, Novartis, P. Permanyer, Physicians' Education Resource, PrIME Oncology, Roche, Shanghai BeBirds, Taiho, Touch Independent Medical Education; Financial Interests, Personal, Leadership Role: AstraZeneca, Lunit, ATORG, CSCO, HKCTS, HutchMed, ASCO, CLCRF, HKCF; Financial Interests, Personal, Stocks or ownership: Aurora Tele-Oncology, Hutchmed, ACT Genomic. All other authors have declared no conflicts of interest.
Resources from the same session
309P - Expression of estrogen receptor is a negative predictive biomarker for immunotherapy with lenvatinib plus pembrolizumab for advanced endometrial cancer with pMMR
Presenter: Hiroyuki Fujii
Session: Poster Display
Resources:
Abstract
310P - A study on the prediction of recurrence site of endometrial cancer using various machine learning techniques
Presenter: Wonkyo Shin
Session: Poster Display
Resources:
Abstract
311P - Circulating cytokines in the differential diagnosis of endometrial cancer
Presenter: Tatyana Abakumova
Session: Poster Display
Resources:
Abstract
312P - Molecular and genetic features of squamous cell carcinoma of vulvar cancer depending on HPV status
Presenter: Visola Navruzova
Session: Poster Display
Resources:
Abstract
313P - Efficacy and safety of oral metronomic chemotherapy in recurrent refractory advanced gynaecological cancer: Experience from regional cancer center of eastern India
Presenter: Ranti Ghosh
Session: Poster Display
Resources:
Abstract
314P - Perioperative outcomes in advanced epithelial ovarian cancer treated with neoadjuvant bevacizumab and chemotherapy: Real-world experience from an Indian cancer centre
Presenter: Upasana Palo
Session: Poster Display
Resources:
Abstract
315P - Real-world experience of niraparib as maintenance therapy in newly diagnosed advanced ovarian cancer: A single-center retrospective study
Presenter: Wenxin Liu
Session: Poster Display
Resources:
Abstract
316P - First evidence of olaparib maintenance therapy in patients with newly diagnosed BRCA wild-type ovarian cancer: A real-world multicenter study
Presenter: Jing Li
Session: Poster Display
Resources:
Abstract
317P - Attitudes of Israeli gynecologists towards risk reduction salpingo-oophorectomy at hysterectomy for benign conditions and the use of hormonal therapy
Presenter: wisam Assaf
Session: Poster Display
Resources:
Abstract
319P - Survival prediction for ovarian cancer patients from Taiwan cancer registry data
Presenter: Tzu-Pin Lu
Session: Poster Display
Resources:
Abstract