565P - Genome-guided targeted therapy combination improves survival in patients with advanced EGFR mutation positive NSCLC failing osimertinib

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

∗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.