Abstract 982P
Background
Previous studies showed that the addition of anti-VEGF inhibitors to erlotinib prolonged progression-free survival (PFS) in EGFR mutated non-squamous non-small-cell lung cancer (Ns-NSCLC) patients (pts). The primary results of WJOG9717L study, open-label, randomized phase II trial comparing Osimertinib (Osi) plus bevacizumab (Bev) with Osi monotherapy for untreated pts with advanced EGFR mutated Ns-NSCLC, were reported at ESMO2021.
Methods
This study enrolled untreated pts with advanced Ns-NSCLC harboring an EGFR sensitizing mutation (Del19 or L858R), and without symptomatic brain metastases. 122 eligible pts were randomized in a 1:1 ratio to receive either Osi (80 mg, daily) plus Bev (15 mg/kg, every 3 weeks) (OB arm) or Osi monotherapy (O arm), and stratified according to sex, stage and EGFR mutation status. The primary endpoint was PFS, assessed by blinded, independent central radiologic reviewer (BICR), and was updated. In exploratory analysis using tissue (pretreatment) and plasma samples (at baseline, cycles 2 and cycle 9), 197 genes were evaluated by targeted deep sequencing.
Results
Between January 2018 and September 2018, 122 pts were enrolled (OB arm, 61 pts O arm, 61 pts). At a median follow-up of 36 months, median updated PFS by BICR was 22.1 months for OB arm and 20.2 months for O arm, with a hazard ratio (HR) of 0.864 (60% CI, 0.711–1.049; 95% CI, 0.549–1.359; one-sided stratified log-rank p=0.202). Updated overall survival (OS) was also not different between two arms with a HR of 1.271 (95% CI, 0.727–2.233) (median OS 33.3 months for OB arm, and 36.5 months for O arm). Among those patients, 94 had evaluable plasma samples at baseline, and 40 had evaluable pretreatment tissue samples. EGFR mutations (76.6%), TP53 mutations (44.7%), EGFR CNV (54.3%) and MET CNV (19.1%) were detected in plasma samples at baseline. In subgroup of patients with TP53 mutations (N=42), median PFS by BICR was 19.8 months for OB arm and 20.2 months for O arm, with a HR of 1.107 (95% CI, 0.534–2.297).
Conclusions
There was also no significant difference in updated PFS between OB arm and O arm, even in patients with TP53 mutations.
Clinical trial identification
UMIN000030206.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
AstraZeneca K.K.
Disclosure
A. Nakamura: Financial Interests, Personal, Invited Speaker: MSD, Thermo Fisher Scientific, AstraZeneca K.K, Eli Lilly Japan K.K., Chugai Pharmaceutical, Taiho Pharmaceutical, Nippon Kayaku, Novartis Pharma. H. Kenmotsu: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co, Ltd., Ono Pharmaceutical Co, Ltd., Boehringer Ingelheim, Eli Lilly K.K, Kyowa Hakko Kirin Co., Ltd., Bristol-Myers Squibb, MSD, Novartis Pharma K.K., Daiichi Sankyo Co., Ltd., AstraZeneca K.K., Pfizer, Taiho Pharma, Merk, Amgen inc., Bayer, Takeda Pharmaceutical Co., Ltd; Financial Interests, Institutional, Research Grant: AstraZeneca, Chugai Pharmaceutical Co, Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co, Ltd., LOXO Oncology, Eli Lilly K.K; Non-Financial Interests, Principal Investigator: AstraZeneca K.K., Eli Lilly K.K, Boehringer Ingelheim, Takeda Pharmaceutical Co., Ltd. K. Sakai: Financial Interests, Personal, Other: Japanese Society of Medical Oncology; Financial Interests, Personal, Invited Speaker: Hitachi, Ltd., Chugai Pharmaceutical Co., Ltd., Life Technologies Japan Co. Ltd. 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. K. Kirita: Financial Interests, Personal, Funding: AstraZeneca. Y. Yoneshima: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K. K. Azuma: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Chugai Pharmaceutical, Takeda Pharmaceutical, MSD. K. Nishino: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Novartis, Pfizer, Takeda Pharmaceutical Company Limited, Merck, Bristol Myers Squibb, Nippon Kayaku; Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly Japan, Pfizer, Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Speaker’s Bureau: Nippon Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: AstraZeneca, Chugai Pharmaceutical, Nippon Boehringer Ingelheim, Eli Lilly Japan, Novartis, Pfizer, Takeda Pharmaceutical Company Limited, Merck, Bristol Myers Squibb, Nippon Kayaku, Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD, AbbVie, Daiichi Sankyo Company, Limited, Amgen, Eisai Co., Ltd. S. Teraoka: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Advisory Board: Pfizer R&D Japan G.K. T. Shukuya: Financial Interests, Institutional, Principal Investigator: AstraZeneca, Chugai Pharmaceutical, MSD; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Novartis, MSD, Taiho Pharma, Daiichi Sankyo, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Kayaku, Pfizer. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K.; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb Co. Ltd, Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K, Shanghai Haihe Biopharm, Pfizer, AstraZeneca K.K; Financial Interests, Institutional, Funding: AstraZeneca K.K., Astellas Pharma Inc., MSD K.K., Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., grants, Pfizer Japan Inc., Bristol Myers Squibb Company, Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Daiichi; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., and Ono Pharmaceutical Co. Ltd.; Non-Financial Interests, Principal Investigator: Ono Pharmaceutical Co. Ltd. and Bristol Myers Squibb Co; Non-Financial Interests, Member: West Japan Oncology Group, Japan Society of Medical Oncology. R. Toyozawa: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical, Eli Lilly Japan, Taiho Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical; Financial Interests, Personal, Other, honoraria: AstraZeneca, Takeda Pharmaceutical, MSD, Pfizer Japan; Financial Interests, Institutional, Invited Speaker: AbbVie, Amgen, Takeda Pharmaceutical, Pfizer Japan, Daiichi Sankyo, Eli Lilly Japan, Novartis Pharma. S. Miura: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, Taiho Pharmaceutical, Ono Pharmaceutical, AstraZeneca, Bristol-Myers Squibb, Pfizer, Eli Lilly, Boehringer Ingelheim Japan, Novartis, MSD, Kyowa Hakko Kirin, Daiichi Sankyo, Amgen, Merck, Takeda Pharmaceutical. D. Fujimoto: Financial Interests, Personal, Invited Speaker: AstraZeneca KK, Ono Pharmaceutical Co Ltd, Bristol-Myers Squibb Co Ltd, Taiho Pharmaceutical Co Ltd, Chugai Pharmaceutical Co Ltd, Merck Sharp & Dohme KK, Boehringer Ingelheim Japan Inc, Kyowa Kirin Co. Ltd, Janssen Pharmaceutical KK. K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Nippon Kayaku Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., CMIC ShiftZero K.K., Life Technologies Japan Ltd., Neo Communication, Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., 3H Clinical Trial Inc., Care Net, Inc., Medical Review Co., Ltd., Medical Mobile Communications co., Ltd, Yodosha Co., Ltd., Nikkei Business Publications, Inc., Japan Clinical Research Operations, CMIC Co., Ltd., Novartis Pharma K.K., TAIYO Pharma Co., Ltd.; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K.; Financial Interests, Institutional, Other, patents sales fee: Daiichi Sankyo Co., Ltd.; Financial Interests, Institutional, Research Grant: PAREXEL International Corp., PRA Health Sciences, EPS Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co., Ltd,., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services Japan K.K., Syneos Health Clinical K.K., Nippon Kayaku Co., Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Takeda Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Sysmex Corporation, Medical Research Support, Eli Lilly Japan K.K., Amgen Inc., Novartis Pharma K.K., Novartis Pharma K.K., SRL, Inc. N. Yamamoto: Financial Interests, Personal, Invited Speaker: MSD K.K, AstraZeneca, Ono Pharmaceutical Co., Ltd., Thermo Fisher Scientific, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim, Novartis, Pfizer Inc., Bristol-Myers Squibb, Nippon Kayaku, GlaxoSmithKline K.K., Sanofi K.K., Hisamitsu Pharmaceutical Co.,Inc., Merk biopharma; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim, Novartis, Bristol-Myers Squibb, Nippon Kayaku, Life Technologies Japan Ltd., Amgen Inc., Guardant Health Japan, Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Research Grant: MSD K.K; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical CO., Ltd., Pfizer Inc., Amgen Inc., Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Funding: Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Toppan Printing, Terumo. K. Nishio: Financial Interests, Personal, Research Grant: Thoracic Oncology Research Group, North East Japan Study Group, Nippon Boehringer Ingelheim Co., Ltd., Clinical Research Support Center Kyushu, West Japan Oncology Group, Nichirei Biosciences Inc., Osaka Minami Hospital, Eli Lilly Japan K.K., Hitachi, Ltd., Sysmex Corporation; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co Ltd, Pfizer Inc., Eli Lilly Japan K.K., MSD K.K., Novartis Pharma K.K., SymBio Pharmaceuticals Limited, AstraZeneca K.K., Amgen Inc., Merck Biopharma Co., Ltd., Roche Diagnostics K.K., Solasia Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Yakult Honsha Co., Ltd., Guardant Health Inc., Takeda Pharmaceuticals, Boehringer Ingelheim Japan, Inc., Fujirebio Inc., Bristol Myers Squibb Company, Janssen Pharmaceutical K.K. T. Takahashi: Financial Interests, Personal, Invited Speaker: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Boehringer Ingelheim Japan, INC, Takeda Pharmaceutical Co Ltd., Yakult Honsha Co. Ltd; Financial Interests, Institutional, Invited Speaker: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Amgen inc., Merck Biopharma CO., Ltd. All other authors have declared no conflicts of interest.