Abstract 1015P
Background
We aimed to assess efficacy and safety of treatment with docetaxel plus ramucirumab or atezolizumab as second-line treatment for PD-L1 negative or weakly positive patients with stage IV non-small-cell-lung cancer (NSCLC) after platinum-based therapy.
Methods
In this multicenter randomized phase III study, we enrolled patients with advanced NSCLC who had progressed during or after a first-line platinum-based chemotherapy regimen. Patients were randomly allocated (1:1) to receive atezolizumab (1200mg/body) (arm A) or docetaxel 60 mg/m2 plus ramucirumab (10 mg/kg) (arm B) every 3 weeks with recommended cross-over on progression. Stratification factors included sex, histology, best response of previous therapy, PD-L1 status, and institution. The primary endpoint was overall survival (OS). Accrual of 420 patients was designed to give 80% power to detect an improvement in median OS from 12 months in the arm A to 16 months in the arm B (hazard ratio (HR) 0.75) with a one-sided α of 0.05.
Results
This study was activated in April 2018 and closed in March 2020 due to slow accrual. 70 patients were enrolled from 26 institutions and all of them were eligible. 36 patients were assigned to the arm A and 34 to the arm B. At a median follow-up of 24.2 months, the median OS was 17.1/15.8 months (HR=1.508, 95% CI, 0.86-2.65; p=0.23). Two-year OS rate was 42.8/19.4% (95%CI, 26.2-58.3/7.5-35.3). ORR was 5.6/35.3% (p=0.002), and the median progression-free survival (PFS) was 1.5/5.5 months (P=0.005). The cross-over rate was 55.6/64.7%, and the median PFS2 was 12.9/9.1 months. Grade 3 or higher toxicities included neutropenia (2.8/17.6%), thrombocytopenia (2.8/8.8%), anorexia (2.8/5.9%), febrile neutropenia (0/5.9%), and hypertension (2.8/8.8%). One patient in the arm B developed bronchopulmonary hemorrhage, leading to death.
Conclusions
The OS was not significantly different between two arms, although the docetaxel plus ramucirumab arm showed favorable ORR and PFS. The 2-year OS rates however suggested that atezolizumab might enhance efficacy of post-study cytotoxic chemotherapy.
Clinical trial identification
UMIN000031584.
Editorial acknowledgement
Legal entity responsible for the study
West Japan Oncology Group.
Funding
Eli Lilly.
Disclosure
Y. Zenke: Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly, Chugai, Boehringer Ingelheim, Ono Pharmaceutical, Bristol Myers Squibb, Takeda Pharmaceutical, Taiho Pharmaceutical, MSD, Novartis, Nippon-Kayaku; Financial Interests, Institutional, Research Grant: AstraZeneca, MSD, Merck, Daiichi Sankyo. S. Niho: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Ono, Chugai, Eli Lilly, Takeda. A. Nakamura: Financial Interests, Personal, Speaker’s Bureau: MSD, Thermo Fisher Scientific, AstraZeneca, Eli Lilly, Chugai Pharmaceutical, Taiho Pharmaceutical, Nippon Kayaku, Novartis. T. Okamoto: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, Johnson & Johnson, MSD, Nippon Boehringer Ingelheim, Nippon Kayaku, Novartis Pharma, Ono Pharmaceutical, Taiho Pharmaceutical, Towa Pharmaceutical; Financial Interests, Institutional, Invited Speaker: AnHeart Therapeutics, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly Japan, Merck Biopharma, MSD, Nippon Kayaku, Novartis Pharma, Pfizer Japan; Financial Interests, Institutional, Funding: Covidien Japan, KM Biologics, Chugai Pharmaceutical, Nippon Boehringer Ingelheim, Nippon Kayaku, Taiho Pharmaceutical. Y. Hosomi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Eisai, Eli Lilly Japan, Taiho Pharmaceutical, Kyowa Kirin, Nippon Kayaku. 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. 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. Yokoyama: Financial Interests, Institutional, Funding: Bristol Myers Squibb, MSD, Takeda Pharmaceutical, Chugai Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Pfizer, Bristol Myers Squibb, Ono Pharmaceutical, Takeda Pharmaceutical, Nippon Kayaku. 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. M. Tsuboi: Financial Interests, Personal, Invited Speaker, Lecture: Johnson & Johnson Japan; Financial Interests, Personal, Advisory Board, Lectures, Advisory boards: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd, MSD; Financial Interests, Personal, Invited Speaker, Lectures: Eli Lilly Japan, Bristol-Myers Squibb KK, Teijin Pharma, Taiho Pharma, Medtronic Japan, Ono Pharmaceutical Co., Ltd; Financial Interests, Personal, Advisory Board, Advisory boards: Novartis; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo company limited, MSD, AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: Boehringer-Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical Co., Ltd, Bristol Myers Squibb KK, Novartis; Financial Interests, Institutional, Invited Speaker: Eli Lilly Japan. All other authors have declared no conflicts of interest.