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Proffered Paper 1

1O - Osimertinib versus gefitinib followed by osimertinib in patients with EGFR-mutant non-small cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE trial

Date

29 Mar 2023

Session

Proffered Paper 1

Topics

Tumour Site

Non-Small Cell Lung Cancer

Presenters

JORDI REMON MASIP

Citation

Journal of Thoracic Oncology (2023) 18 (4S): S35-S88.
<article-id>elcc_Ch01

Authors

J. REMON MASIP1, S. Ponce Aix2, A. Callejo Perez3, K. Al-rabi4, R. Bernabe Caro5, L. Greillier6, M. Majem Tarruella7, N. Reguart Aransay8, I. Monnet9, S. Cousin10, P. Garrido Lopez11, G. Robinet12, R. Garcia Campelo13, A. Madroszyk Flandin14, J. Mazieres15, H. Curcio16, Y. Pretzenbacher17, A.C. Dingemans18, R. Dziadziuszko19

Author affiliations

  • 1 Villejuif/FR
  • 2 Hospital Universitario 12 de Octubre, Madrid/ES
  • 3 Vall d'Hebron University Hospital, Barcelona/ES
  • 4 KHCC - King Hussein Cancer Center, Amman/JO
  • 5 Hospital Universitario Virgen del Rocio, Seville/ES
  • 6 Hopital St. Marguerite Assistance Publique Hopitaux de Marseille, Marseille/FR
  • 7 Hospital de la Santa Creu i Sant Pau, 08025 - Barcelona/ES
  • 8 Hospital Clinic y Provincial de Barcelona, Barcelona/ES
  • 9 Chi De Creteil, Creteil/FR
  • 10 Institut Bergonie, Bordeaux/FR
  • 11 Hospital Universitario Ramon y Cajal, Madrid/ES
  • 12 CHRU de Brest - Hopital Morvan, 29200 - Brest/FR
  • 13 CHUAC - Complexo Hospitalario Universitario A Coruña, A Coruña/ES
  • 14 IPC - Institut Paoli-Calmettes, Marseille, Cedex/FR
  • 15 Centre Hospitalier Universitaire de Toulouse - Hopital Larrey, Toulouse/FR
  • 16 Centre Francois Baclesse, Caen/FR
  • 17 EORTC AISBL/IVZW - European Organisation for Research and Treatment of Cancer, Brussels/BE
  • 18 Erasmus MC - University Medical Center, Rotterdam/NL
  • 19 Medical University of Gdansk, Gdansk/PL

Resources

This content is available to ESMO members and event participants.

Abstract 1O

Background

APPLE is a 3 arms phase II non-comparative trial exploring the sequential treatment approach of gefitinib followed by osimertinib or osimertinib frontline in patients with advanced EGFR-mutant NSCLC. Here we report the exploratory analysis of the outcome with osimertinib frontline compared to a sequential approach.

Methods

Patients were randomized to: arm A (osimertinib until RECIST progression -PD-), arm B (gefitinib until the emergence of circulating tumor DNA EGFR T790M mutation or RECIST PD) or arm C (gefitinib until RECIST PD), and then switch to osimertinib in both arms B and C. In this analysis, arms B and C were pooled. Primary endpoint: Progression Free Survival rate “on osimertinib” at 18 months (PFSR-OSI-18) in arm B (H0: PFSR-OSI-18 of ≤40%). Secondary endpoints: overall survival (OS) and Brain PFS (BPFS). Primary analyses were performed in per-protocol population (PPP). In all arms, contrast-enhanced brain CT-scan was performed every 8 weeks.

Results

From 11/2017 to 02/2020, 156 patients were randomized (arm A:53, arm B/ C:103), and 136 were included in the PPP. Most patients were females (56.6% and 69.9%), with EGFR Del19 (66% and 64%). Baseline brain metastases: 19% and 29.1%, respectively. In pooled arms B/C, 70% of patients received osimertinib at PD. In arm A, PFS on osimertinib was 19.5 months. The PFSR-OSI-18 was 51.1% in Arm A and 61% in pooled arms B/C. The median OS was NR in arm A vs 42.8 (95% CI: 28.6-NR) months (mo) in pooled arm B/C, with 18-months OS of 84.4% and 82.3%, respectively. In all arms, 68 brain progression events were observed. Median time to brain PD in arm A and B/C were 34.3 mo (95% confidence interval, CI:26.9-NR) and 22.3 mo (95%CI:18.6–22.3), and corresponding hazard ratio was 0.54 (90% CI: 0.34–0.86) with 18-months BPFS of 82.2% and 63.5%, respectively.

Conclusions

In advanced EGFR mutant-NSCLC, upfront treatment with osimertinib shows a significant reduction in the risk of brain progression, with comparable OS versus the sequential treatment approach.

Clinical trial identification

NCT02856893.

Legal entity responsible for the study

EORTC.

Funding

AstraZeneca.

Disclosure

J. Remon Masip: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, MSD, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, Takeda, Sanofi; Financial Interests, Personal, Expert Testimony: OSE Immunotherapeutics; Non-Financial Interests, Personal, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Personal, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca; Non-Financial Interests, Personal, Member, Secretary of the Lung Cancer Group at the EORTC: EORTC. 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. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Eli Lilly, Pfizer, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, AbbVie, BMS, MSD, Novartis, Sanofi, Takeda, Pfizer, PharmaMar. N. Reguart Aransay: Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, Bayer, Novartis, Sanofi, Janssen, AstraZeneca, Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Boehringer Ingelheim, Guardant, BMS, Pfizer, Amgen, Novartis. I. Monnet: Other, Personal, Other, invitation to virtual ASCO 2021 and 2022: Pfizer; Other, Personal, Other, invitation to ESMO congress 2021 and 2022: Takeda. P. Garrido Lopez: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BMS, GlaxoSmithKline, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Sanofi, Daiichi Sankyo, Sanofi; Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Advisory Board, Spouse: Boehringer Ingelheim, Gebro, Janssen, Nordic; Financial Interests, Personal, Invited Speaker, Spouse: Boehringer Ingelheim, Janssen; Financial Interests, Personal, Other, Data monitoring committee for INC280I12201 trial in 2020: Novartis; Financial Interests, Personal, Invited Speaker, CACZ885V2201C_CANOPY-N trial: Novartis; Financial Interests, Personal, Other, Lung Cancer Medical Education TASC Committee 2021: Janssen; Financial Interests, Institutional, Invited Speaker: Novartis, Janssen, AstraZeneca, Pfizer, Blue print, Apollomics, Amgen, Array Biopharma; Financial Interests, Personal, Invited Speaker, IO102-012/KN-764 trial: IO Biotech; Financial Interests, Personal, Invited Speaker, JNJ-61186372 (JNJ-372) Clinical Development Program: Janssen; Non-Financial Interests, Personal, Leadership Role, Council member as Women for Oncology Committee ChairFellowship and Award Committee and Press CommitteeFaculty for lung and other thoracic tumours: ESMO; Non-Financial Interests, Personal, Leadership Role, President of the Spanish Federation of Medical Societies (FACME) 2020-2022Past President 2023-2024: FACME; Non-Financial Interests, Personal, Leadership Role, Former President of Spanish Medical Oncology Society: SEOM; Non-Financial Interests, Personal, Leadership Role, Member of the Scientific Committee of the Spanish Against Cancer Research Foundation (AECC) and also Board member: AECC; Non-Financial Interests, Personal, Leadership Role, IASLC Women in Thoracic Oncology Working Group Member: IASLC; Non-Financial Interests, Personal, Advisory Role, Member of the Spanish National Health Advisory Board: Spanish Minister of Health; Non-Financial Interests, Personal, Advisory Role, Assessment for lung cancer screening evaluation: EUnetHTA; Non-Financial Interests, Personal, Advisory Role: Spanish National Evaluation network (RedETS); Non-Financial Interests, Personal, Advisory Role, scientific advisory group member for clinical immunological, oncology and lung cancer areas: EMA; Other, Personal, Other, My son is working in the pharma company TEVA as an engineer. I do not have any kind of relationship with TEVA: TEVA. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Sanofi, Amgen, Bayer, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Takeda, Eli Lilly, Janssen, Pfizer, AstraZeneca, Eli Lilly, Amgen, Daiichi Sankyo, Roche, Roche, JNJ, Mirati; Financial Interests, Institutional, Research Grant: Amgen; Non-Financial Interests, Personal, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Personal, Member: IASCL, ASCO, AACR. All other authors have declared no conflicts of interest.

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