VP3_2021 - A randomized phase II study of second-line osimertinib (Osi) and bevacizumab (Bev) versus Osi in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) and T790M mutations (mt): Results from the ETOP BOOSTER trial

Abstract

R. Soo1, J-Y. Han2, G. Dimopoulou3, B.C. Cho4, C.M. Yeo5, E. Nadal6, E. Carcereny7, J. de Castro8, M.A. Sala9, R. Bernabe10, L. Coate11, M. Provencio12, R. Garcia Campelo13, S. Cuffe14, S. Hashemi15, M. Früh16, B. Ruepp17, H. Roschitzki-Voser17, R. Stahel18, S. Peters19
1Medical Oncology, National University Hospital, Singapore, 2Medical Oncology, Goyang National Cancer Center, Goyang, Republic of Korea, 3Statistical Office, Frontier-Science Foundation Hellas, Athens, Greece, 4Medical Oncology, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea, 5Medical Oncology, Tan Tock Seng Hospital, Singapore, 6Medical Oncology, Catalan Institute of Oncology, IDIBELL, L'Hospitalet, Barcelona, Spain, 7Medical Oncology, Hospital Universitari Germans Trial i Pujol, Badalona, Spain, 8Medical Oncology, Hospital la Paz, Madrid, Spain, 9Medical Oncology, Hospital Basurto, Bilbao, Spain, 10Medical Oncology, Hospital Virgen del Rocio, Seville, Spain, 11Medical Oncology, University Hospital Limerick, Limerick, Ireland, 12Medical Oncology, Hospital Puerta de Hierro, Madrid, Spain, 13Medical Oncology, Hospital Teresa Herrera, La Coruña, Spain, 14St James’s Hospital and Cancer Trials Ireland, Dublin, Ireland, 15Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, Netherlands, 16Medical Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland, 17Coordinating Center, European Thoracic Oncology Platform (ETOP), Bern, Switzerland, 18European Thoracic Oncology Platform (ETOP), Bern, Switzerland, 19Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois - CHUV, Lausanne, Switzerland

Background: Whilst Osi is the standard treatment (TX) in patients (pts) with advanced NSCLC with sensitising EGFR-mt and acquired T790M-mt, progression inevitably occurs. Preclinical studies suggest the angiogenic pathway is implicated in EGFR tyrosine kinase inhibitor (TKI) resistance. The study objective was to determine the efficacy and safety of combined Osi/Bev versus Osi in pts with NSCLC with EGFR-mt (exon 19 del or L858R) and T790M-mt at progression on prior EGFR TKI.

Methods: BOOSTER is an open-label randomized phase II trial. Eligible pts were equally randomized to Osi (80 mg QD) and Bev (15 mg/kg i.v. Q3W) versus Osi. Primary end point was investigator assessed progression free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), and adverse events (AEs). The trial was designed to detect an increase in the median PFS from 11 months (m) with Osi to 17.2m with Osi/Bev (HR 0.64, at 5% 1-sided alpha and 80% power, 126 PFS events; 154 pts).

Results: Between 05/2017-02/2019, 155 pts were randomized: 78 Osi/ Bev, 77 Osi. The median age was 67 years, 62% females, 40% current-former (c-f) smokers, 30% ECOG PS 0, stage IIIb-c/IVa/IVb: 1%/70%/28%, 59% non-Asians. At a median follow-up of 34m, the median PFS was 15.4m (95% CI 9.2-18.0) and 12.3m (6.2-17.2) (PFS events: 64 & 65) in the Osi/Bev and Osi arm respectively (HR 0.96; 0.68- 1.37; p=0.83). Median OS was 24.0m (17.8-32.1) in Osi/Bev and 24.3m (16.9-37.0) in Osi arm (deaths: 46 & 43) (HR 1.03; 0.67-1.56; p=0.91). ORR was 55% in both arms. Smoking history exhibits significant TX interaction for both PFS and OS (adjusted p= 0.0052 & 0.029); PFS HR 0.52/1.47, OS HR 0.59/1.54, for c-f/never smokers, respectively. Median time to TX discontinuation was 12.4m/8.2m in Osi/Bev and 10.8m in Osi. Grade≥3 TX-related AEs occurred in 47% pts in Osi/Bev (Grade 5: 0 pt) and 18% in Osi (Grade 5: 3 pts).

Conclusions: No difference in PFS was observed between Osi/Bev and Osi. A significant TX interaction with smoking history is identified in subgroup analysis, indicating superiority of Osi/Bev vs. Osi for c/f smokers.

Clinical trial identification: NCT03133546.

Legal entity responsible for the study: European Thoracic Oncology Platform (ETOP).

Funding: AstraZeneca (study drug and study support) and Roche (study drug).

Disclosure:
R. Soo: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Lilly, Merck, Novartis, Pfizer, Roche, Taiho, Takeda, Yuhan; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Lilly, Merck, Novartis, Otsuka, Pfizer, Roche, Synthorx, Taiho, Takeda, Yuhan.
J. Han: Financial Interests, Personal and Institutional, Other, Honoraria: Roche, AstraZeneca, Takeda; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Lilly, MSD, BMS, Pfizer, Medpacto; Financial Interests, Personal and Institutional, Research Grant: Roche, Pfizer, Ono, Takeda.
B.C. Cho: Financial Interests, Personal, 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.; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Medpacto, Blueprint Medicines; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio Therapeutics, Kanaph Therapeutic Inc, Cyrus Therapeutics, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Board: Kanaph Therapeutic Inc, Brigebio Therapeutics, Cyrus Therapeutics, Guardant Health, Oscotec Inc.; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics.
E. Nadal: Financial Interests, Personal, Funding: Roche, Pfizer, Merck-Serono, BMS; Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, Merck-Serono, Pfizer, Lilly, Amgen, Boehringer-Ingelheim, AstraZeneca, Takeda.
E. Carcereny: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Roche, Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Expert Testimony: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Other, Travel / Accommodation / Expenses: Bristol-Myers Squibb, Pfizer, Roche, Takeda.
J. de Castro: Financial Interests, Personal and Institutional, Other, Educational fees: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp and Dohme, Novartis, F. Hoffmann-La Roche; Financial Interests, Personal and Institutional, Advisory Board: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, F. Hoffmann-La Roche, Sanofi, Takeda; Financial Interests, Personal and Institutional, Speaker’s Bureau: AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme, F. Hoffmann-La Roche.
M.A. Sala: Non-Financial Interests, Institutional, Other, Travel grants: Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, MSD, Mylan, Pfizer, Pharma Mar, Pierre Fabre, Roche; Non-Financial Interests, Institutional, Speaker’s Bureau: Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, MSD, Mylan, Pfizer, Pharma Mar, Pierre Fabre, Roche; Non-Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, MSD, Mylan, Pfizer, Pharma Mar, Pierre Fabre, Roche.
L. Coate: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Daiichi.
M. Provencio: Financial Interests, Personal and Institutional, Advisory Board: BMS, AstraZeneca, Roche, MSD, Lilly.
R. Garcia Campelo: Financial Interests, Personal, Advisory Board: MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda, Janssen; Financial Interests, Personal, Invited Speaker: MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda, Janssen; Financial Interests, Personal, Advisory Role: MSD, Bristol-Myers, Roche, Boehringer Ingelheim, Pfizer, Novartis, AstraZeneca, Lilly, Takeda, Janssen.
S. Cuffe: Financial Interests, Personal, Other, travel grants: MSD, Pfizer, Roche.
S. Hashemi: Financial Interests, Personal and Institutional, Invited Speaker: AbbVie, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, GSK, Janssen, MSD, Novartis, Roche, Takeda, Xcovery; Financial Interests, Personal and Institutional, Research Grant: AbbVie, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, GSK, Janssen, MSD, Novartis, Roche, Takeda, Xcovery; Financial Interests, Personal and Institutional, Principal Investigator: AbbVie, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, GSK, Janssen, MSD, Novartis, Roche, Takeda, Xcovery; Financial Interests, Personal and Institutional, Advisory Role: AbbVie, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, GSK, Janssen, MSD, Novartis, Roche, Takeda, Xcovery.
M. Früh: Financial Interests, Personal, Advisory Role: BMS, MSD, AstraZeneca, Boehringer Ingelheim, Roche, Takeda, Pfizer; Non-Financial Interests, Institutional, Research Grant: BMS; AstraZeneca.
R. Stahel: Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Janssen, MSD, Pfizer, Regeneron, Roche, Seattle Genetics, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Blueprint, Eli Lilly, GSK, MSD, Novartis, Roche, Sandoz; Financial Interests, Institutional, Research Grant: Roche, AstraZeneca, BMS, MSD, Pfizer.
S. Peters: Financial Interests, Personal and Institutional, Advisory Role: AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffman-La Roche, Foundation Medicine, Illumina, Janssen, Novartis , PharmaMar, Pfizer, Regeneron, Sanofi, Seat; Financial Interests, Personal and Institutional, Speaker’s Bureau: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Novartis, Pfizer, Sanofi, Takeda, Merck Sharp and Dohme, Medscape, Imedex; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F. Hoffman-La Roche, Illumina, Novartis, Pfizer, Merck Sharp and Dohme, Merck Serono; Financial Interests, Personal, Expert Testimony: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Novartis, Pfizer, Sanofi, Takeda, Merck Sharp and Dohme, Medscape.
All other authors have declared no conflicts of interest.