16MO - Clinical impact of plasma EGFR analysis: Results from the ETOP-BOOSTER randomized phase II trial

Background

The ETOP-BOOSTER study explored the addition of bevacizumab to osimertinib as 2^nd-line treatment in patients with pathologically confirmed advanced NSCLC harboring common sensitising EGFR (70% Exon 19 deletion; 30% Exon 21 L858R) and acquired EGFR T790M mutations (mt) and reported no difference in progression-free survival (PFS). An interaction of treatment outcomes by smoking status was previously identified. Pre-specified exploratory analysis of serial plasma samples using next generation sequencing (NGS) is reported.

Methods

Plasma circulating tumour DNA (ctDNA) analysis was conducted using Guardant360^® on samples collected prospectively at baseline (BL), week 9 (w9) and at disease progression (PD). Multivariable Cox models, including interaction of treatment with smoking history, plasma EGFR T790M and TP53 mt at BL and longitudinally, and tumour EGFRmt status were analysed to assess their effect on outcome.

Results

From the 155 randomised patients, 136 (87%) had available blood samples at BL (68 in each arm), 110 (71%) at w9 and 65 (42%) at PD for plasma NGS analysis. EGFR T790M mt was detected in 71% (97/136) of BL samples and was not associated with PFS (table). At w9, EGFR T790M mt was undetected in 91% (of 80 available, initially mt, cases), while at PD it was present in 34% (of 47 cases available). Smoking status was found to be predictive for PFS (interaction p = 0.046), however it was not associated with TP53 mt, which was detected in 63% of BL samples. BL TP53 mt and tissue EGFR Exon 21 L858R were each found to be poor prognostic factors for PFS and overall survival independent of treatment.

Conclusions

The interaction of treatment with smoking, was confirmed for PFS in the current evaluation, and was not found to be driven by the presence of TP53 or EGFR T790M mt. BL TP53 mt and EGFR Exon 21 L858R were associated with poor outcome.

Clinical trial identification

EudraCT 2016-002029-12/ETOP 10-16 BOOSTER.

Legal entity responsible for the study

ETOP IBCSG Partners Foundation.

Funding

Has not received any funding.

Disclosure

R.A. Soo: Other, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Janssen, Eli Lilly, Merck, Merck Serono, Novartis, Pfizer, Puma, Roche, Taiho, Takeda, Thermo Fisher, Yuhan; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim. U. Dafni: Financial Interests, Personal, Other, Member of the Tumor Agnostic Evidence Generation working Group: Roche. J. Han: Financial Interests, Institutional, Research Grant: Roche, Ono, Pfizer, Takeda; Other, Personal, Advisory Board: BMS, Merck, Novartis, Pfizer, Takeda, Abion, Jint Bio, Janssen; Financial Interests, Personal, Funding, Honoraria: AstraZeneca, Takeda, Merck, Pfizer, Novartis, Yuhan, Ingenium Therapeutics, Onecure Gen, Janssen. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Other, Advisory role: Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Invited Speaker: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Eli Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Other, Personal, Other, Founder: DAAN Biotherapeutics. E. Nadal: Financial Interests, Institutional, Research Grant: Roche, Pfizer, Merck-Serono, Bristol Myers Squibb, Nanostring; Non-Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck-Serono, Pfizer, Eli Lilly, Amgen, Boehringer Ingelheim, AstraZeneca, Takeda, Janssen, Daiichi-Sankyo, Sanofi, Bayer. E. Carcereny: Other, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Roche, Takeda; Other, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Institutional, Research Grant: Merck; Other, Personal, Other: Bristol-Myers Squibb, Pfizer, Roche, Takeda. M.A. Sala Gonzalez: Non-Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Roche, PharmaMar; Financial Interests, Personal, Funding, Meeting, Travel: Roche; Financial Interests, Personal, Funding, Meeting, Travel: Takeda; Financial Interests, Personal, Invited Speaker, Honoraria: Roche, PharmaMar, Takeda. M. Provencio Pulla: Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Roche, Takeda, Pfizer, Janssen; Other, Personal, Invited Speaker, Honoraria: BMS, AstraZeneca, Takeda, Pfizer, MSD, Roche. C. Britschgi: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Roche, Takeda, Janssen-Cilag, Boehringer Ingelheim, Merck KGaA, Sanofi; Other, Personal, Funding, Travel, Meeting: AstraZeneca; Financial Interests, Personal, Funding, Travel, Meeting: Takeda. R. Kammler: Non-Financial Interests, Personal, Leadership Role: ESBB. S.P. Finn: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Bayer, BMS, Merck, Roche, Takeda. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: Pharma Mar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020–2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP/EORTC/SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice-President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. R.A. Stahel: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Blueprint, Boehringer Ingelheim, GSK, MSD, Novartis, Roche, BMS; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, MSD, Pfizer, Roche, Sandoz, Seattle Genetics, Takeda, Boehringer Ingelheim, GSK; Financial Interests, Personal, Other, DMC: Takeda; Financial Interests, Personal, Other, Editor in Chief: Lung Cancer; Financial Interests, Personal, Other, Editor: CTR; Financial Interests, Institutional, Research Grant, ETOP study: Roche, AstraZeneca, BMS, MSD, Pfizer, Mirati, Janssen; Financial Interests, Institutional, Research Grant, IBCSG study: Novartis, Ipsen, Pierre Fabre, MSD, Pfizer, Roche, AstraZeneca, Celgene; Non-Financial Interests, Personal, Invited Speaker, President Foundation Council: IBCSG, ETOP. All other authors have declared no conflicts of interest.