Abstract 1025P
Background
DOC monotherapy is an optional Japanese standard of care for chemo-naïve elderly patients (pts) with advanced NSCLC. DOC+RAM showed superior survival benefit over DOC in second-line for NSCLC. A Japanese phase II study comparing DOC+RAM and DOC showed febrile neutropenia (FN) incidence of one-third in DOC+RAM. DOC+RAM could be a promising candidate for elderly NSCLC pts, but such high FN incidence is a critical concern. We thus adopted a routine primary prophylactic PEG-G-CSF to reduce FN and maximize the efficacy of DOC+RAM in elderly pts.
Methods
This is a multicenter prospective single arm phase II trial for chemo-naïve elderly pts (aged ≥75) with advanced NSCLC. Intravenous DOC (60 mg/m2, day 1) + RAM (10 mg/kg, day 1) with subcutaneous PEG-G-CSF (3.6 mg, day 2) was administered every 3 weeks until progression. The primary endpoint was overall response rate (ORR) (threshold: 20% and expected: 35%).
Results
Between February 2018 and January 2021, 54 pts were enrolled, but this trial was terminated before full enrollment (n=65), because of slow accrual. Median age was 78 (range, 75-86). Forty (74%) adenocarcinoma, 8 (15%) squamous carcinoma, and 6 (11%) others were included. Twenty-one (38.9%) PR, 22 (40.7%) SD, 9 (16.7%) PD, and 2 (3.7%) NE were confirmed, resulting in ORR of 38.9% (90% confidence interval [CI]: 27.7-51.0%) and disease control rate of 79.6%. Median progression-free survival and overall survival were 5.2 (95%CI: 4.2-6.9) and 12.7 (95%CI: 10.2-18.9) months, respectively. There were 1 (2%) FN, 2 (4%) bleeding ≥G3, and 1 (2%) treatment-related death. Pneumonitis occurred in 5 (9%) pts (2 G1, 1 G2, 1 G3, and 1 G5). As for adverse events (incidence ≥5%), hematological toxicities ≥G3: 4 (7%) thrombocytopenia; and 3 (6%) neutropenia, while non-hematological toxicities ≥G3: 6 (11%) hyponatremia; 5 (9%) infection; 5 (9%) hypertension; 4 (7%) anorexia; and 3 (6%) oral mucositis were observed.
Conclusions
DOC+RAM with PEG-G-CSF demonstrated efficacy and safety for elderly NSCLC pts. Primary prophylactic PEG-G-CSF highly prevented FN.
Clinical trial identification
UMIN000030598.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Eli Lilly.
Disclosure
T. Tokito: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, AstraZeneca, MSD, Novartis, Bristol Myers Squibb. A. Hata: Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal, Research Grant: Eli Lilly, Boehringer Ingelheim, AstraZeneca; Financial Interests, Personal, Invited Speaker: Eli Lilly, Chugai, Pfizer, AstraZeneca, Boehringer Ingelheim. M. Tachihara: Financial Interests, Personal, Research Grant: AstraZeneca K.K.; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co Ltd AstraZeneca K.K., Eli Lilly Japan K.K., MSD K.K., Nippon Kayaku, Takeda Pharmaceutical Co., Ltd. H. Tanaka: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Eli Lilly, MSD, Ono Pharmaceutical, Merck, Novartis, Takeda Pharmaceutical, Pfizer, Daiichi Sankyo Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Chugai Pharmaceutical, Merck, AstraZeneca, MSD, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Merck, Takeda Pharmaceutical, Taiho Pharmaceutical, Pfizer, Daiichi Sankyo Pharmaceutical, AbbVie. Y. Sato: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Novartis, Chugai Pharmaceutical, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical; Financial Interests, Invited Speaker: Nippon Kayaku, Bristol Myers Squibb, Bristol Myers Squibb, Takeda, Kyowa Kirin. 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. K. Wakuda: Financial Interests, Personal, Research Grant: Chugai Pharmaceutical Co., Ltd, AstraZeneca, Novartis, AbbVie, Amgen, MSD, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd, Taiho Pharmaceutical, Boehringer Ingelheim, Eli Lilly K.K, Ono Pharmaceutical, MSD, AstraZeneca, Daiichi Sankyo, Janssen Pharmaceutical K.K., Takeda Pharmaceutical. A. Nakamura: Financial Interests, Personal, Invited Speaker: MSD, Thermo Fisher Scientific, AstraZeneca, Eli Lilly Japan K.K., Chugai Pharmaceutical, Taiho Pharmaceutical, Nippon Kayaku, Novartis Pharma. 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. 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. All other authors have declared no conflicts of interest.