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
122P - Distinct transcriptomic immune profiling and clinicopathological features of cribriform morphology in colorectal adenocarcinomas
Presenter: Abdelhakim Khellaf
Session: Poster Display
Resources:
Abstract
123P - Spatial molecular profiling identifies FGF20 upregulation on cancer-associated fibroblast and FGFR2-PI3K/Akt activation in tumor cells of sporadic early-onset colon cancer
Presenter: Dave Hoon
Session: Poster Display
Resources:
Abstract
124P - Characteristics, prognosis and therapeutic effects of non-V600 BRAF mutated colorectal cancer
Presenter: Lalida Arsa
Session: Poster Display
Resources:
Abstract
125P - Final results of APOLLON-11 and SOYUZ-APOLLON study: Multicentre prospective observational post-authorization study of bevacizumab biosimilar in patients with metastatic colorectal cancer in real-world practice
Presenter: Alexey Tryakin
Session: Poster Display
Resources:
Abstract
126P - From tumor height (TH) to tumor regression grade (TRG) in locally advanced rectal cancers (LARC) during total neadjuvant therapy (TNT): A retrospective analysis
Presenter: Valeria Pusceddu
Session: Poster Display
Resources:
Abstract
127P - A meta-analysis of efficacy and safety from head-to-head first-line (1L) trials of epidermal growth factor receptor inhibitors (EGFRIs) versus bevacizumab in combination with chemotherapy (CT) doublets in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) by sidedness
Presenter: Takayuki Yoshino
Session: Poster Display
Resources:
Abstract
128TiP - A phase II study of cadonilimab + FOLFOXIRI and bevacizumab as initial therapy for unresectable proficient mismatch repair/microsatellite stable (pMMR/MSS) metastatic colorectal cancer (mCRC)
Presenter: Rongbo Lin
Session: Poster Display
Resources:
Abstract
140P - Prevalence of claudin-18 isoform 2 (CLDN18.2) positivity in locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mg/GEJ) adenocarcinoma in patients (pts) in the Asia region: Phase III SPOTLIGHT and GLOW studies
Presenter: Hoo Hwoei Fen Soo
Session: Poster Display
Resources:
Abstract
141P - Early phase trials outcomes in refractory upper GI cancers: A 10-year analysis from the SCRI UK phase I unit
Presenter: Antonella Cammarota
Session: Poster Display
Resources:
Abstract
142P - The survival impact of the addition of durvalumab to cisplatin/gemcitabine in advanced biliary tract cancer: A real-world, retrospective, multicentric study
Presenter: Silvia Foti
Session: Poster Display
Resources:
Abstract