The EMOO in Asia Study established a clinical annotated population-based registry of lung cancer in a collaboration between ESMO, the International Agency for Research on Cancer, and partner institutions in Indonesia, Malaysia and Singapore and Thailand.
A retrospective study was conducted based on incident lung cancer cases diagnosed between 2017 – 2019 in Lampang (Thailand), Penang (Malaysia), and Yogyakarta (Indonesia) and a clinical case series obtained from the National Cancer Center in Singapore. Tumour and clinical information were abstracted by chart review according to a predefined study protocol.
Among 2,962 lung cancer cases with a specified pathological diagnosis (87%), the largest proportion of patients had non-squamous NSCLC (76%). For cases with staging information (92.1%), the majority presented with metastatic disease (71%). Overall, rates for molecular testing in the 1,528 patients with stage IV non-squamous NSCLC were 67.0% for EGFR, 42% for ALK, 39% for ROS1, 8% for BRAF and 36% for PD-L1. Among these patients, first line systemic treatment included chemotherapy (26%), targeted therapy (36%), and immunotherapy (6%), with 31% of patients without a record of antitumor treatment. The respective actuarial 1-year survival was 48%, 77%, 68% and 12%. The rates of EGFR mutation testing in Lampang, Penang, Yogyakarta and Singapore was 14%, 59%, 73% and 97%, respectively. Of the patients tested, 58% had EGFR mutations detected. The actuarial 1-year survival was 77% for patients with EGFR mutations and received targeted therapy, 36% for patients tested positive but did not receive target treatment and 44% without detectable EGFR mutations. Molecular testing and the proportion of patients receiving treatment were highly heterogenous between the regions.
Molecular testing rates was heterogenous and survival outcomes varied depending on targeted therapy status and access to treatment. An understanding of testing and treatment factors may improve patient access to optimal treatment.
ESMO and IARC.
Foundation or academic group WITH funding from a pharma, biotech, or other commercial company - AstraZeneca, Roche, Novartis.
R. Stahel: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Blueprint; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Institutional, Other: AstraZeneca; Financial Interests, Institutional, Other: BMS; Financial Interests, Institutional, Other: Daiichi Sankyo; Financial Interests, Institutional, Other: Celgene; Financial Interests, Institutional, Other: Ipsen; Financial Interests, Institutional, Other: Janssen; Financial Interests, Institutional, Other: Mirati; Financial Interests, Institutional, Other: MSD; Financial Interests, Institutional, Other: Novartis; Financial Interests, Institutional, Other: Pfizer; Financial Interests, Institutional, Other: Pierre Fabre; Financial Interests, Institutional, Other: Roche. R. Kanesvaran: Financial Interests, Institutional, Invited Speaker: Astellas; Financial Interests, Institutional, Invited Speaker: Johnson and Johnson; Financial Interests, Institutional, Advisory Board: Johnson and Johnson; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Invited Speaker: Ipsen; Financial Interests, Institutional, Advisory Board: Ipsen; Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board: Ferring; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Johnson and Johnson; Non-Financial Interests, Personal, Leadership Role, Past President: Singapore Society of Oncology; Non-Financial Interests, Personal, Leadership Role, President: SIOG; Non-Financial Interests, Personal, Leadership Role, Vice Chairman: Singapore Cancer Society; Non-Financial Interests, Personal, Leadership Role, Medical Advisory Board Member: International Kidney Cancer Coalition. N. Prasongsook: Financial Interests, Personal, Advisory Board: Roche (Thailand); Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Pfizer. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody; Financial Interests, Institutional, Advisory Board: Takeda; Financial Interests, Institutional, Invited Speaker: Takeda; Financial Interests, Institutional, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Invited Speaker: Roche/Genentech; Financial Interests, Institutional, Advisory Board: Roche/Genentech; Financial Interests, Institutional, Advisory Board: Regeneron; Financial Interests, Institutional, Invited Speaker: RTP; Financial Interests, Institutional, Advisory Board: Phosplatin Therapeutics; Financial Interests, Institutional, Advisory Board: PharmaMar; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: PRIME; Financial Interests, Institutional, Invited Speaker: PER; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Mirati; Financial Interests, Institutional, Advisory Board: Merck Serono; Financial Interests, Institutional, Invited Speaker: Medscape; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Advisory Board: Incyte; Financial Interests, Institutional, Invited Speaker: Imedex; Financial Interests, Institutional, Advisory Board: Illumina; Financial Interests, Institutional, Invited Speaker: Illumina; Financial Interests, Institutional, Advisory Board: IQVIA; Financial Interests, Institutional, Advisory Board: GlaxoSmithKline; Financial Interests, Institutional, Advisory Board: Gilhead; Financial Interests, Institutional, Advisory Board: Genzyme; Financial Interests, Institutional, Advisory Board: Foundation Medicine; Financial Interests, Institutional, Invited Speaker: Fishawack; Financial Interests, Institutional, Advisory Board: F-Star; Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier; Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Ecancer; Financial Interests, Institutional, Advisory Board: Debiopharm; Financial Interests, Institutional, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board: Blueprint Medicines; Financial Interests, Institutional, Advisory Board: Biocartis; Financial Interests, Institutional, Advisory Board: Bio Invent; Financial Interests, Institutional, Advisory Board: BeiGene; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Arcus; Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: AbbVie; Financial Interests, Institutional, Advisory Board: iTheos; Financial Interests, Institutional, Advisory Board: Novocure; Financial Interests, Institutional, Invited Speaker: OncologyEducation; Financial Interests, Institutional, Invited Speaker: RMEI; Financial Interests, Institutional, Invited Speaker: Mirati; 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); Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member: ASCO; Non-Financial Interests, Personal, Member: AACR; Non-Financial Interests, Personal, Member: IASLC; 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. Soo: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Lily; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Conference sponsorship: Taiho; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Yuhan; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Atypical epidermal growth factor receptor (EGFR) mutations spanning exons 18 to 21 account for 10–15% of cases of EGFR-mutated non-small cell lung cancer (NSCLC). Afatinib is the only EGFR tyrosine kinase inhibitor (TKI) approved to treat these mutations. The combination of amivantamab, an EGFR-MET bispecific antibody, and lazertinib, a 3rd generation EGFR TKI, is being evaluated in patients with atypical EGFR mutations.
CHRYSALIS-2 (NCT04077463) is an ongoing open-label study with an expansion cohort (C) examining amivantamab + lazertinib in advanced NSCLC with atypical non-exon 20 insertion EGFR mutations (eg, S768I, L861Q, G719X). Patients may have received ≤2 prior lines of therapy, which may include one 1st- or 2nd-generation EGFR TKI. Patients receive 1050 mg IV amivantamab (1400 mg for bodyweight ≥80 kg) weekly in cycle 1 and every other week thereafter + 240 mg oral lazertinib daily. Response is assessed by the investigator per RECIST v1.1.
For this interim analysis (data cutoff June 8, 2022), 40 patients were response evaluable (had ≥1 post baseline disease assessment or discontinued for any reason). The median age of the patients was 64 years, 47.5% were female, and 19/40 had prior therapy (1 prior line of therapy in 17/40 and 2 prior lines in 2/40). Exon 19 G719X mutation accounted for most of the mutations (60.0%), with many of these patients having compound mutations. A best response of partial response (PR) was observed in 60.0% (24/40). Responses were seen in both treatment naïve as well as post-afatinib treated patients. The median duration of response was not evaluable. Of the 30 patients who had ≥3 scheduled post baseline assessments or discontinued for any reason, the objective response rate was 56.7%, with 16 (53.3%) achieving a confirmed PR (median duration of response was not evaluable) and 1 (3.3%) had an unconfirmed PR. No new safety signals or concerns were identified.
Among a patient population with few treatment options, amivantamab combined with lazertinib demonstrated encouraging anti-tumor activity in a majority of patients with a tolerable safety profile.
NCT04077463.
Kristen Evaul, Katharine Fang, and Ashley Oney, Cello Health, Communications/MedErgy.
Janssen Research & Development.
Janssen Research & Development.
B.C. Cho: Financial Interests, Personal, Other, Consulting role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Joseah BIO; Financial Interests, Personal, Invited Speaker: Gencurix Inc, Interpark Bio Convergence Corp.; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Institutional, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp.; Other, Personal, Other, Founder: DAAN Biotherapeutics. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Genzyme Corporation, Chugai pharmaceutical, Eisai, Inivata, Ipsen, Turning Point Therapeutics. M.E. Marmarelis: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novocure, AstraZeneca, Janssen, Takeda, Bristol Myers Squibb, Ikena; Financial Interests, Personal, Other, CME talk: Blueprint Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Gilead, Merck, Portola Pharmaceuticals, Bluebird Biosciences, Novartis, Janssen, Pfizer; Financial Interests, Institutional, Invited Speaker: Janssen, AstraZeneca, Oncotelic, Eli Lilly; Financial Interests, Institutional, Research Grant: Takeda. K. Goto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Amoy Diagnosties Co.,Ltd., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., DAIICHI SANKYO Co., Ltd., Eisai Co., Ltd., Guardant Health Inc., Merck Biopharma Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K.; Financial Interests, Personal, Expert Testimony: Medpace Japan K.K.; Financial Interests, Personal and Institutional, Funding: Amgen Inc., Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., DAIICHI SANKYO Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Ignyta,Inc., Janssen Pharmaceutical K.K., KISSEI PHARMACEUTICAL CO., Ltd., Kyowa Kirin Co., Ltd., Loxo Oncology, Inc., MEDICAL ＆ BIOLOGICAL LABORATORIES CO., Ltd., Merck Biopharma Co., Ltd., Merus N.V., MSD K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sumitomo Dainippon Pharma Co., Ltd., Spectrum Pharmaceuticals, Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics,Inc.; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association. S. Lee: Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Merck; Financial Interests, Personal, Advisory Board: Merck, Roche, AstraZeneca, Pfizer. J. Neal: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech/Roche, Exelixis, Jounce Therapeutics, Takeda Pharmaceuticals, Eli Lilly and Company, Calithera Biosciences, Amgen, Iovance Biotherapeutics, Blueprint Pharmaceuticals, Regeneron Pharmaceuticals, Natera, Sanofi/Regeneron, D2G Oncology, Surface Oncology, Turning Point Therapeutics, Mirati Therapeutics; Financial Interests, Institutional, Funding: Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Nektar Therapeutics, Takeda Pharmaceuticals, Adaptimmune, GSK, Janssen, AbbVie; Other, Personal, Other, Honoraria: CME Matters, Clinical Care Options CME, Research to Practice CME, Medscape CME, Biomedical Learning Institute CME, MLI Peerview CME, Prime Oncology CME, Projects in Knowledge CME, Rockpointe CME, MJH Life Sciences CME, Medical Educator Consortium, HMP Education. J. Curtin: Financial Interests, Institutional, Full or part-time Employment: Johnson and Johnson; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. J.M. Bauml: Financial Interests, Personal, Full or part-time Employment: Janssen Research and Development; Financial Interests, Personal, Stocks/Shares: Janssen Research and Development. J. Mahoney: Financial Interests, Personal, Full or part-time Employment: Janssen R&D. L. Trani: Financial Interests, Personal, Full or part-time Employment: Janssen. R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment, I am an employee of Janssen Oncology R&D and therefore received salary and long-term compensation in the form of company stocks: Janssen Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson. P. Tomasini: Non-Financial Interests, Personal, Research Grant: Roche, AstraZeneca, Takeda, BMS, BI, Novartis. All other authors have declared no conflicts of interest.
MET Amplification (METamp) commonly mediates resistance to EGFR TKIs in NSCLC patients with EGFR-mutation. Several clinical trials showed that the combination of MET inhibition with EGFR TKI is a promising therapeutic strategy to overcome the MET amplification-mediated resistance. SCC244 is a highly selective small molecular inhibitor of MET kinase. It was well tolerated and has shown favorable anti-tumor activities in patients with MET aberration as monotherapy in clinical studies.
This is an open-label Phase Ib/II study (NCT: 04338243) to evaluate the safety and efficacy of SCC244 combined with Osimertinib in pts with locally advanced or metastatic EGFR-mut NSCLC, which carries METamp and was resistant to EGFR TKI. 30 pts received combined treatment of SCC244 at 200mg QD or 300mg QD, and Osimertinib at a fixed dose of 80mg QD until disease progression or intolerable toxicity in Phase Ib. Tumor response was assessed every 6 weeks. The primary endpoint for Phase Ib was ORR (RSCIST v1.1) by investigator.
Overall, ORR was 60% [95% CI:40.6, 77.3], mDOR was 5.8 months [95% CI:3.9, 12.7 ], mPFS was 6.9 months [95% CI: 3.9, 8.9] and mOS was 16.9 months [95% CI:11.1, NE ]. Among 19 pts with EGFR-mut, T790M negative NSCLC who progressed on 1st or 2nd generation EGFR TKI, ORR was 73.7%[95% CI: 48.8, 90.9], mDOR was 6.2 months [95% CI: 3.3, NE], mPFS was 7.0 months [95% CI: 4.1, 13.8] and mOS was 15.1 months [95% CI:9.5, NE ]. In 30 pts, the most common AE was Oedema (70.0%). The most common grade ≥3 TRAEs were Thrombocytopenia (16.7%) and Neutropenia (16.7%). 6 pts discontinued due to TRAEs, none were solely attributed to SCC244.
SCC244 plus Osimertinib demonstrated clinical activity in EGFR-mutant NSCLC pts with METamp and resistant to EGFR TKI. The safety profile was acceptable and manageable.
NCT: 04338243.
Haihe Biopharma Co., Ltd.
Haihe Biopharma Co., Ltd.
M. Sun, J. Zhang, M. Li, Y. Ren: Other, Institutional, Full or part-time Employment: Haihe Biopharma Co., Ltd. All other authors have declared no conflicts of interest.
ALC is approved as first-line (1L) treatment for advanced ALK+ NSCLC based on the global Phase 3 ALEX study, which reported a significant PFS benefit for ALC vs CRZ (HR 0.43, 95% CI 0.32–0.58) and a clinically meaningful improvement in 5-year OS (62.5 vs 45.5%). Primary analysis of ALESIA confirmed PFS benefit of 1L ALC in Asian pts with advanced ALK+ NSCLC; we present updated data from ALESIA (cutoff date: 16 May 2022) after ≥5 years follow-up.
Pts had stage IIIB/IV ALK+ NSCLC by central IHC and ECOG PS 0–2. Asymptomatic CNS metastases (mets) were allowed. Pts were randomised 2:1 to ALC 600mg BID (n=125) or CRZ 250mg BID (n=62), stratified by ECOG PS (0/1 vs 2) and baseline CNS mets (yes vs no). Regular tumour/CNS imaging was performed. Primary endpoint: PFS by investigator (INV). Secondary endpoints included: time to CNS progression, ORR, DOR, OS and safety.
At the updated data cutoff (median duration of follow-up 61 months [m] ALC, 51 m CRZ), a durable PFS benefit was seen for ALC vs CRZ (HR 0.33, 95% CI 0.23–0.49; median PFS [INV] 41.6 vs 11.1 m) and a clinically meaningful improvement in OS (HR 0.60, 95% CI 0.37–0.99; 5-year OS rate 66.4 vs 56.0%; pts remaining at risk 69 vs 25). PFS/OS benefit of ALC occurred in pts with or without CNS mets at baseline (Table) and across pre-specified subgroups. More CRZ pts (77.1 vs 61.8% ALC) received ≥1 anti-cancer therapy post-PD, with ALC the most widely used ALK TKI. Asymptomatic CNS PD was more common in CRZ pts (25.8 vs 10.4% ALC); treatment beyond asymptomatic CNS PD was longer with ALC vs CRZ (median 11.2 vs 3.9 m). ALC had a favourable safety profile vs CRZ despite longer treatment duration (42.3 vs 12.6 m), with fewer Grade 3–5 AEs (48 vs 55%), serious AEs (28 vs 29%) or AEs leading to treatment discontinuation (11 vs 15%).
With ≥5 years follow-up, 1L alectinib 600mg BID continues to provide clinical benefit to Asian pts with advanced ALK+ NSCLC, with no new safety concerns. mets, metastases; NE, not evaluable; pts, patients.
With CNS mets at baseline Without CNS mets at baseline ALC (n=44) CRZ (n=23) ALC (n=81) CRZ (n=39) Median PFS (INV), months 42.3 9.2 41.6 12.7 HR 0.17 (95% CI 0.09–0.33) HR 0.45 (95% CI 0.29–0.71) Median OS, months NE 46.2 NE NE HR 0.40 (95% CI 0.19–0.85) HR 0.81 (95% CI 0.42–1.55) 5-year OS rate, % 63.6 39.3 67.8 64.9 Pts remaining at risk, n 25 6 44 19 ALC (n=125) CRZ (n=62) ORR (INV), n (%) 114 (91.0) 48 (77.0) Median DOR (INV), months 44.3 9.4 HR 0.33 (95% CI 0.22–0.50)
NCT02838420.
Medical writing support for the development of this abstract, under the direction of the authors, was provided by Fiona Duthie, PhD, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
C. Zhou: Financial Interests, Personal, Invited Speaker: Roche, Lily China, Hengrui, Qilu, MSD, C—Stone. Y. Lu: Non-Financial Interests, Personal, Invited Speaker: BeiGene, Roche/Genentec, AstraZeneca, Pfizer; Non-Financial Interests, Personal, Advisory Role: Roche/Genentech, AstraZeneca, Pfizer, Bristol Myers Squibb, Merck Sharp & Dohme, BeiGene; Non-Financial Interests, Personal, Leadership Role: Roche/Genentech, AstraZeneca, BeiGene. S. Kim: Non-Financial Interests, Personal, Invited Speaker: Amgen, Boehringer Ingelheim, Janssen, Norvatis, Takeda; Financial Interests, Personal, Research Grant: Yuhan; Non-Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Norvatis, Takeda, Yuhan. T. Baisamut (reungwetwattana): Financial Interests, Personal, Advisory Board, and speaker: Astrazeneca, Pfizer, Roche, MSD, Novartis, BMS, Amgen; Financial Interests, Personal, Advisory Board: Yuhan; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, Novartis, MSD. S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Merck, Pfizer, Lilly; Financial Interests, Personal, Research Grant: AstraZeneca, Merck. L. Bu: Financial Interests, Personal, Full or part-time Employment: Roche. L. Qian: Financial Interests, Personal, Full or part-time Employment: Roche Pharma Product Development China. V.R. Archer: Financial Interests, Personal, Full or part-time Employment: Roche Productslimited. M. Hilton: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. M. Zhou: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. L. Zhang: Financial Interests, Personal, Research Grant: AZ, BMS, Roche; Financial Interests, Personal, Principal Investigator: Noratis, Hansoh pharm, KeLun Pharm, QiLu pharm. All other authors have declared no conflicts of interest.
Envonalkib (TQ-B3139, Env) is a novel small molecule ALK/ROS1/c-Met inhibitor. Here, we presented the primary analysis results of a phase III trial, aiming to evaluate the efficacy and safety of Env versus crizotinib (Cri) in advanced ALK-positive NSCLC patients (pts) who had not received a prior ALK inhibitor.
Eligible pts with ALK-positive and inoperable stage IIIB-IV NSCLC who had not received a prior ALK inhibitor and had received <2 prior lines of chemotherapy were randomized 1:1 to receive Env (600mg, bid, d1-d28) or Cri (250mg, bid, d1-d28) until disease progression or intolerable toxicity. Pts were stratified by baseline brain metastases (present vs. absent) and number of prior chemotherapy lines (0 vs. 1). The primary endpoint was PFS assessed by IRC according to RECIST v1.1. Secondary endpoints included confirmed ORR, DCR, DoR, OS, CNS-ORR, CNS-DoR, CNS-TTP and safety.
From Aug 21, 2019 to Jul 13, 2020, 131 pts were assigned to Env and 133 to Cri. At data cutoff (Oct 14, 2021), the median follow-up was 13.80 m in Env and 10.12 m in Cri. The mPFS by IRC was significantly longer with Env than with Cri (NE vs. 11.89 m; HR 0.46, p < 0.0001). Subgroup analyses of PFS by IRC showed that the efficacy of Env was better than Cri in each subgroup. Confirmed ORR was 81.68% in Env and 69.92% in Cri. Treatment with Env was associated with more durable response (mDoR: NE vs 12.68 m, p=0.0014) than Cri. For pts without BMs at baseline, the incidence of BMs during treatment period in Env significantly lower than that in Cri (1.10% vs 11.83%, p=0.0049). The CNS-ORR in pts with intracranial target lesions at baseline was 78.95% for Env vs. 23.81% for Cri. OS data are immature. Drug-related grade ≥3 TEAEs occurred in 51.91% (Env) vs. 40.60% (Cri). TEAEs led to treatment discontinuation of Env in 4.58% and Cri in 3.01%. Pts with TP53 mutation could also benefit from Env treatment (mPFS: 11.93 vs 7.85 m, HR 0.47). Pts with progressive disease in Env did not develop new insurmountable resistance mutations.
Compared with Cri, Env significantly prolonged PFS in advanced ALK-positive NSCLC pts who had not received a prior ALK inhibitor, and showed greater advantages in controlling BMs. The safety profiles following Env treatment were manageable.
NCT04009317.
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
All authors have declared no conflicts of interest.
Tepotinib, a MET TKI, is approved for METex14 skipping NSCLC in several Asian countries. In VISION (N=313; data cut-off: Feb 20, 2022), tepotinib demonstrated durable clinical activity with an objective response rate (ORR) of 50.8% and a median (m) duration of response (DOR) of 18.0 months. Tepotinib also showed promising intracranial activity in patients (pts) with brain metastases. We report data from all 106 Asian pts with METex14 skipping NSCLC enrolled in VISION.
Pts with advanced METex14 skipping NSCLC, detected by liquid (L+) and/or tissue biopsy (T+) received tepotinib 500 mg (450 mg active moiety) once daily. Primary endpoint: objective response (RECIST 1.1) by IRC. Secondary endpoints included disease control (DCR), DOR, progression-free survival (PFS), overall survival (OS), and safety (analysis sets: T+, L+, T+ and/or L+).
In 106 Asian pts enrolled in VISION (Japan - 38, South Korea - 20, Taiwan -12, China - 30, outside Asia - 6), median age was 70.5 yrs (range 52–89), 39.6% were female, 43.4% had smoking history, 79.2% had adenocarcinoma, 73.6% had ECOG PS 1, and 47.2% were treatment-naïve. 45.3% were L+ and 78.3% were T+. ORR was 57.5% (95% CI: 47.6, 67.1), DCR was 80.2% (71.3, 87.3), mDOR was 18.5 months (10.4, ne), mPFS was 13.8 months (9.6, 19.9), and mOS was 23.7 months (19.3, ne). In treatment naïve pts (n=50), ORR was 66.0% (51.2, 78.8), and in previously treated pts (n=56), ORR was 50.0% (36.3, 63.7). Meaningful activity was observed irrespective of METex14 skipping detection method (Table). Treatment-related adverse events (TRAEs) occurred in 95.3% of pts; 38.7% had Grade ≥3 TRAEs. TRAEs led to dose reduction in 30.2%, and permanent discontinuation in 13.2% of pts. Most common adverse events were peripheral edema (65.1%), creatinine increase (42.5%), and hypoalbuminemia (40.6%). CI, confidence interval; L+, METex14 skipping detected by liquid biopsy; ne, not estimable; T+, METex14 skipping detected by tissue biopsy. *25 patients had METex14 skipping detected by both liquid and tissue biopsy.
Endpoint* L+ Asian patients n=48 T+ Asian patients n=83 ORR, % (95% CI) 58.3 (43.2, 72.4) 60.2 (48.9, 70.8) DCR, % (95% CI) 72.9 (58.2, 84.7) 84.3 (74.7, 91.4) DOR Median, months (95% CI) 18.5 (8.3, ne) 13.4 (9.7, ne) PFS Median, months (95% CI) 11.0 (6.7, 19.9) 14.7 (10.8, 24.9) OS Median, months (95% CI) 19.9 (13.1, ne) 26.8 (19.6, ne)
Tepotinib demonstrated robust and durable efficacy, with a manageable safety profile, in Asian pts with METex14 skipping NSCLC in VISION.
NCT02864992.
Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by Syneos Health, London, UK.
Merck Healthcare KGaA, Darmstadt, Germany.
Merck Healthcare, KGaA, Darmstadt, Germany.
J.C. Yang: Financial Interests, Institutional, Advisory Board: Astrazeneca, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Novartis, Bayer, GSK, Takeda Oncology, Puma Pharmaceuticals, Ono Pharmaceuticals, Merck Serono, MSD, Pfizer, Eli Lilly, Roche/Genentech, Janssen; Financial Interests, Institutional, Invited Speaker: Astrazeneca, Boehringer Ingelheim, Novartis, Astrazeneca, MSD, Ipsen, Takeda Oncology; Financial Interests, Personal, Advisory Board: Yuhan Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Dizal Pharmaceutical, Novartis, Numab, Merck, Daiichi Sankyo, Eli Lilly, Bayer, Janssen; Non-Financial Interests, Personal, Leadership Role, Board of Director: IASLC; Non-Financial Interests, Personal, Member: ASCO. T. Kato: Financial Interests, Personal, Advisory Board, speaker, consultancy: AstraZeneca, Eli Lilly, Merck Biopharma, MSD; Financial Interests, Personal, Advisory Board, speaker: Pfizer; Financial Interests, Personal, Other, consultancy: Daiichi-Sankyo, Takeda, Taiho; Financial Interests, Personal, Other, consultancy, speaker: Chugai; Financial Interests, Personal, Invited Speaker: Ono, Novartis; Financial Interests, Personal, Advisory Board: BeiGene, Glaxo; Financial Interests, Personal, Full or part-time Employment, Family member: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Chugai, MSD, Pfizer, AstraZeneca, Eli Lilly, AbbVie, Regeneron, Novartis, Amgen, Merck Biophama, Haihe Biopharma, Blueprint Medicines, Turning Point. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Takeda, MSD, Yuhan, Amgen, Alpha Pharmaceutical, Janssen, BMS, Roche, Daichi Sankyo. H. Sakai: Financial Interests, Personal, Speaker’s Bureau: BMS, Ono Pharmaceutical, MSD K K, AstraZeneca, Chugai Pharma, Taiho Pharmaceutical, Boehringer Ingelheim, Merck Healthcare KGaA Darmastadt Germany. M. Morise: Financial Interests, Personal, Speaker’s Bureau: Chugai, MSD, ONO, AstraZeneca. J. Han: Financial Interests, Personal, Funding: Hoffman-La Roche Ltd., ONO, Pfizer, Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Takeda, Medpacto, Abion, ONO; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, F Hoffmann-La Roche Ltd., Merck Sharpe & Dohme, Takeda. J.L. Huang, K. Berghoff, H. Vioix: Financial Interests, Personal, Other, Employee: Merck Healthcare, KGaA, Darmstadt, Germany. R. Bruns: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare, KGaA, Darmstadt, Germany; Financial Interests, Personal, Stocks/Shares: Merck Healthcare, KGaA, Darmstadt, Germany. G.P. Otto: Financial Interests, Personal, Other, Employee: Merck Healthcare, KGaA, Darmstadt, Germany; Financial Interests, Personal, Other, Stocks: Novartis. X. Le: Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, EMD Serono an affiliate of Merck KGaA; Financial Interests, Personal, Research Grant: Eli Lilly, Boehringer Ingelheim. P.K. Paik: Financial Interests, Personal, Advisory Role: Calithera, Takeda, Xencor, CrownBio, Bicara, Mirati, EMD Serono an affiliate of Merck KGaA; Financial Interests, Institutional, Research Grant: Bicara, Boehringer Ingelheim, EMD Serono an affiliate of Merck KGaA. All other authors have declared no conflicts of interest.
Osimertinib (osi) is a 3rd-gen CNS active EGFR-TKI for EGFRm NSCLC. In the Ph III ADAURA (NCT02511106) primary analysis adjuvant osi showed a significant DFS benefit vs placebo (PBO) in resected EGFRm NSCLC, with a low frequency of osi dose modifications/discontinuations and no new safety signals observed. We report exploratory analyses of long-term safety data from ADAURA.
Eligible patients (pts; completely resected EGFRm stage IB–IIIA [AJCC 7th edition] NSCLC ± adjuvant CT) were randomised (682 globally) 1:1 to osi 80 mg QD or PBO for up to 3 yrs. Safety assessments were performed at baseline, wk 2, 4 and 12, then every 12 wks until treatment was completed/discontinued, and at day 28 after treatment stopped. Post hoc analyses of most common/AEs of clinical interest over time, and a summary of AEs by sex, were exploratory. DCO: 11 April 2022.
The safety set included: osi n=337; PBO n=343. Median duration of treatment exposure was 35.8 (osi) and 25.1 (PBO) months. The majority of pts in both arms reported an AE (any) with first onset between 0–12 months (osi 97%, PBO 86%). The proportion of pts reporting AEs with first onset after 12 months was low (osi 1%, PBO 4%). Dose interruptions/reductions/discontinuations of treatment due to AEs were 27/12/13% with osi and 13/1/3% with PBO. Stomatitis was the most common AE leading to dose reduction (osi 3%, PBO 0%); diarrhoea was the most common leading to interruption (osi 4%, PBO 1%). ILD was reported in 11 pts (3%; all Gr 1/2) in the osi arm and no pts in the PBO arm, and was the most common AE leading to discontinuation (osi 3%). The incidence of AEs (any), SAEs and AEs leading to discontinuation were similar between male and female pts. All fatal AEs were considered unrelated to treatment: osi n=1 (respiratory failure); PBO n=2 (pulmonary embolism, unknown AE).
Osi was well tolerated over a prolonged treatment duration. Most AEs developed within the first 12 months of treatment, with a low proportion first reported after 12 months. There was no meaningful difference in AE incidence by sex. Combined with significant efficacy benefit, these data support long-term treatment with osi as standard of care in EGFRm stage IB–IIIA resected NSCLC.
NCT02511106.
The authors would like to acknowledge Rachel Gater, PhD, of Ashfield MedComms, an Inizio company for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
AstraZeneca.
AstraZeneca.
T. John: Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Ignyta, Novartis, Bayer. C. Grohe: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel Fees: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme. J.W. Goldman: Financial Interests, Personal, Other, Research Support: Advaxis, Array, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, Genentech, G1 Therapeutics, Merck, Pfizer; Financial Interests, Personal, Other, Travel Fees: AstraZeneca; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Genentech, Pfizer. F. de Marinis: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Novartis, Pfizer, Takeda, Roche, MSD, X-Covery. T. Kato: Financial Interests, Personal, Advisory Role: AstraZeneca, Amgen Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly and Company, Merck Serono, Merck Sharp & Dohme, Pfizer, Daiichi-Sankyo; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Amgen Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly and Company, Merck Serono, Merck Sharp & Dohme, Pfizer, Bristol Myers Squibb, Novartis, Taiho Pharmaceutical, Boehringer Ingelheim, Roche; Financial Interests, Personal, Full or part-time Employment, Spouse: Eli Lilly and Company; Financial Interests, Personal, Other, Research Support: AstraZeneca, Amgen Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly and Company, Merck Serono, Merck Sharp & Dohme, Pfizer, Novartis, AbbVie Inc., Regeneron. J. Choi: Financial Interests, Personal, Other, Research Support: AstraZeneca, Roche, Samyang Biopharmaceuticals Corporation (Korea), Yuhan Corporation (Korea). B. Melotti: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi, Sun Pharmaceutical Industries Ltd.; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi, Sun Pharmaceutical Industries Ltd.; Financial Interests, Personal, Principal Investigator: AstraZeneca, Bristol Myers Squibb, Novartis, Roche, Sanofi. M.D. Fidler: Financial Interests, Personal, Advisory Role: AstraZeneca, BeiGene, Biodesix, Daiichi Sankyo, G1 Therapeutics, Genentech, Janssen, Gilead, Jazz Pharmaceuticals, Rakuten, Silverback Therapeutics; Financial Interests, Personal, Other, Research Support: Alkermes, Astellas, AstraZeneca, Biodesix, Genentech, Pfizer, Rakuten; Financial Interests, Personal, Writing Engagements: Gilead. L. Sainsbury: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Stachowiak: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. S. Taggart: Financial Interests, Personal, Full or part-time Employment: Exploristics; Financial Interests, Personal, Full or part-time Employment, Contracted: AstraZeneca. Y. Wu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Novartis, Takeda; Financial Interests, Personal, Other, Research Support: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Hengrui, Roche; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Beigen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Merck Sharp & Dohme, Pfizer, Roche, Sanofi. M. Tsuboi: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck Sharp & Dohme, Novartis, Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Research Support: Boehringer Ingelheim, Merck Sharp & Dohme, AstraZeneca, Ono Pharmaceuticals Co. Ltd., Bristol Myers Squibb, Eli Lilly and Company, Novartis, MIRXES Japan; Financial Interests, Personal, Invited Speaker: Johnson & Johnson, AstraZeneca, Eli Lilly and Company, Chugai Pharmaceuticals Co. Ltd., Taiho Pharma, Medtronic Japan Co., Ltd., Ono Pharmaceutical Co. Ltd., Merck Sharp & Dohme, Bristol Myers Squibb, Teijin Pharma. R.S. Herbst: Financial Interests, Personal, Advisory Role: AstraZeneca, Bolt Biotherapeutics, Bristol Myers Squibb, Candel Therapeutics, Inc., Checkpoint Therapeutics, Cybrexa Therapeutics, DynamiCure Biotechnology, LLC, eFFECTOR Therapeutics, Inc., Eli Lilly and Company, EMD Serono, Genentech, Gilead, HiberCell, Inc., I-Mab Biopharma, Immune-Onc Therapeutics, Inc., Immunocore, Janssen, Johnson and Johnson, Loxo Oncology, Mirati Therapeutics, NextCure, Novartis, Ocean Biomedical, Inc., Oncocyte Corp, Oncternal Therapeutics, Pfizer, Regeneron Pharmaceuticals, Revelar Biotherapeutics, Inc., Ribbon Therapeutics, Roche, Sanofi, Xencor, Inc; Financial Interests, Personal, Research Grant: AstraZeneca, Eli Lilly and Company, Genentech/Roche, Merck and Company; Financial Interests, Personal, Leadership Role: American Association for Cancer Research, International Association for the Study of Lung Cancer, Society for Immunotherapy of Cancer, Southwest Oncology Group; Financial Interests, Personal, Member of the Board of Directors, (non-executive/independent): Immunocore, Junshi Pharmaceuticals. M. Majem Tarruella: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca; Financial Interests, Personal, Other, Research Support: Bristol Myers Squibb, Roche, AstraZeneca; Financial Interests, Personal, Other, Honoraria: Pfizer, Helsinn, Sanofi, Mundipharma, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Roche, Kyowa Kyrin, Pierre Fabre, Takeda, Bayer, Amgen Inc. All other authors have declared no conflicts of interest.
Osimertinib, a 3rd-generation EGFR-TKI, is the preferred 1L treatment for EGFRm advanced NSCLC; however, resistance eventually develops. ELIOS (NCT03239340) characterised resistance mechanisms to 1L osimertinib with a primary objective comparing paired tumour tissue biopsies from baseline (BL) and after PD. We report exploratory analyses of concordance between tissue and plasma testing from BL and post-PD samples and PFS by detected plasma EGFRm at BL and by plasma EGFRm clearance at 8 wks post-treatment.
Pts with EGFR-TKI naïve advanced NSCLC with an EGFR-TKI-sensitising mutation received osimertinib 80 mg QD in 28-day cycles. Mandatory tumour biopsies were obtained pre-treatment and after PD. Concordance between tissue and plasma tumour testing was assessed via NGS at BL and post-PD. Plasma EGFRm (Ex19del/L858R only) analysis was conducted at BL and wk 8 by ddPCR. Clearance was defined as undetected EGFRm ctDNA at wk 8, where it was detected at BL.
154 pts were enrolled: 77% Asian, Ex19del/L858R/atypical EGFR mutations 55/38/7%. Concordance was high between tissue and plasma NGS at BL (n=118) and PD (n=50) for point mutations, e.g., sensitising EGFRm (BL: 109 samples, 80% concordance; PD: 45 samples, 87% concordance). Amplifications were detected more frequently in tissue than plasma at PD, e.g., MET (PD: 12 samples, 33% concordance). Plasma better captured tumour heterogeneity at PD, including point mutations (EGFR C797S; RAS) and fusions (RET). Of 136 pts with evaluable ctDNA at BL, 111 had detected plasma EGFRm. Median (95% CI) PFS in pts with vs without detectable BL EGFRm was 15.7 (11.3–20.2) vs 36.8 (9.1–not calculable) months. Of 104 pts with evaluable ctDNA at BL and wk 8, 94 had plasma EGFRm clearance at wk 8. Median (95% CI) PFS in pts with clearance was 19.6 (14.3–23.8) months and not calculated in pts without clearance due to the low number of events (9 events in 10 pts).
Concordance between tissue and plasma NGS at BL and PD was high for point mutations but lower for amplifications which were detected more frequently in tissue. Our data support the prognostic importance of plasma EGFRm detection at BL and its early clearance during treatment.
NCT03239340.
The authors would like to acknowledge Caroline Allinson, BSc, of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
AstraZeneca.
AstraZeneca.
M. Ahn: Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, MSD, Merck, ONO, Takeda, Yuhan, Amgen , Pfizer, Novartis, Roche, Alpha-pharmaceuticals; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Lilly, MSD, Merck, Ono, Takeda, Yuhan, Amgen, Pfizer, Novartis, Roche. B.C. Cho: Financial Interests, Personal, Advisory Role: AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, BridgeBio Therapeutics, Bristol Myers Squibb, Cyrus Therapeutics, Eli Lilly and Company, Guardant Health, Janssen, KANAPH Therapeutics, Inc., MedPacto, Merck Sharp & Dohme, Novartis, Ono Pharmaceuticals Co., Ltd., Oscotec, Inc., Pfizer, Roche, Takeda, Yuhan Corporation; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio. Convergence Corp., J INTS BIO.; Financial Interests, Personal, Other: DAAN Biotherapeutics; Financial Interests, Personal, Research Grant: AbbVie Inc., AstraZeneca, Bayer, Blueprint Medicines, Champions Oncology, Dizal Pharma, Dong-A ST, Eli Lilly and Company, GI Innovation, Inc., Interpark Bio. Convergence Corp., Janssen, MedPacto, MOGAM Biotechnology Research Institute, Merck Sharp & Dohme, Novartis, Ono Pharmaceuticals Co., Ltd., Yuhan Corporation; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Stocks/Shares: BridgeBio Therapeutics, Cyrus Therapeutics, Gencurix, Inc., Interpark Bio. Convergence Corp., J INTS BIO., KANAPH Therapeutics, Inc., TheraCanVac, Inc. Y.K. Pang: Financial Interests, Personal, Principal Investigator: AstraZeneca. P.J. Voon: Financial Interests, Personal, Advisory Role: AstraZeneca, Ipsen, Merck Sharp & Dohme, Novartis, Pfizer. S. Kim: Financial Interests, Personal, Other: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Novartis, Roche; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Novartis, Yuhan Corporation. J. De Castro Carpeno: Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, Takeda, TESARO, Inc.; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Gilead, Merck Sharp & Dohme, Pfizer, Roche, Takeda. M. Tiseo: Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Amgen Inc., AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Laboratoires Pierre Fabre, Merck-Serono, Merck Sharp & Dohme, Novartis, Otsuka Pharmaceutical, Pfizer, Roche, Sanofi, Takeda. J. Li: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. L. Servidio: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S. Sadow: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Markovets: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. K.H. Tang: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. Z. Piotrowska: Financial Interests, Personal, Advisory Role: AstraZeneca, Blueprint Medicines, C4 Therapeutics, Cullinan Oncology, Daiichi Sankyo, Eli Lilly and Company, Janssen, Takeda; Financial Interests, Personal, Principal Investigator: AstraZeneca, Cullinan Oncology; Financial Interests, Personal, Research Grant: AbbVie Inc., AstraZeneca, Blueprint Medicines, Cullinan Oncology, Daiichi Sankyo, Janssen, Novartis, Spectrum Pharmaceuticals, Inc., Takeda, Tesaro, Inc.