1482P - Multicenter pharmacokinetic study of pembrolizumab for non-small cell lung cancer in elderly adults aged over 75 years

Background

Pembrolizumab (Pemb) is a key drug for the treatment of advanced or recurrent non-small cell lung cancer (NSCLC). However, there are limited data on Pemb use in older adults aged >75 years with NSCLC, especially in terms of pharmacokinetics (PK).

Methods

This open-label multicenter observational study aimed to evaluate real-world data on the safety, efficacy, and blood concentrations of Pemb (both monotherapy and combination therapies) in older adults with NSCLC. Blood samples for PK analysis were collected immediately before Pemb administration. Quantitative Pemb concentrations were measured by liquid chromatography-mass spectrometry.

Results

We enrolled 100 patients from July 2019 to September 2020; one patient was excluded due to stage migration. Patient characteristics were as follows: median age, 78 (75–87) years; male/female ratio, 70/29; performance status (PS) 0–1/2–3, 85/14; adenocarcinoma/squamous cell carcinoma/others, 62/25/12; stage I–III/IV/postoperative recurrence (TNM 7th edition), 9/60/30; PD-L1 TPS <1%/1%–49%/≥50%, 12/31/48; and monotherapy/combination therapy, 65/34. The best overall efficacy was CR/PR/SD/PD (7/40/32/20), and the response rate was 47.5%. The median progression-free survival (PFS) and overall survival (OS) were 8.0 and 19.0 months, respectively. The adverse event profile was generally similar to that reported in previous studies. In total, 77 blood samples were collected immediately before the second cycle (C1 trough). Although no clear association between Pemb concentrations and patient background was found, PFS and OS were significantly shortened in the population with low C1 trough, a population characterized by lower PS, high number of metastatic organs at the beginning of treatment, and low blood albumin level.

Conclusions

In older adults aged >75 years with NSCLC and low albumin levels and PS and a high number of metastatic organs, C1 trough of Pemb is reduced and not expected to prolong PFS and OS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

AMED.

Disclosure

J. Sakakibara-Konishi: Financial Interests, Institutional, Research Grant: Lilly. T. Kurata: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Pfizer, Bristol Myers, Takeda, Eli Lilly, Chugai, Nippon Kayaku, Yansen, AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: MSD, Takeda. K. Watanabe: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Ono Pharmaceutical, BMS, Boehringer Ingelheim, Merck, MSD, Takeda Pharmaceutical. Y. Hosomi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Ono Pharmaceutical, Bristol Myers Squibb, Eli Lilly, Taiho Pharmaceutical, Chugai Pharmaceutical, Kyowa Kirin, Takeda, Nippon Kayaku, Eisai, Novartis, Towa Pharmaceutical. H. Horinouchi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, BMS/Ono, Merck Sharp & Dohme, Roche/Chugai, Novartis, Pfizer, Boehringer Ingelheim, Kyowa Kirin, Nihon Kayaku, AbbVie, Roche/Chugai; Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, BMS/Ono, Merck Sharp & Dohme, Roche/Chugai, Amgen, Nihon Kayaku; Financial Interests, Institutional, Research Grant: Roche/Chugai, Merck Sharp & Dohme, Daiichi Sankyo, Ono Pharmaceutical, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AbbVie. Y. Ohe: Financial Interests, Personal, Advisory Board: Amgen, AnHeart Therapeutics Inc, AstraZeneca, BMS, Celltrion, Janssen, Nippon Kayaku, Ono, Pfizer, Takeda; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Chugai, Eisai, Eli Lilly, MSD, Novartis, Ono, Takeda; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Janssen, Amgen; Financial Interests, Personal and Institutional, Invited Speaker: Takeda, Ono; Non-Financial Interests, Leadership Role: JSMO, JLCS, JCOG; Non-Financial Interests, Member: ASCO. Y. Nakahara: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Bristol Myers Squibb, Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca, Taiho Pharmaceutical Co., Ltd., Nippon Kayaku Co.,Ltd.; Financial Interests, Institutional, Research Funding: Takeda Pharmaceutical Company Limited. T. Asao: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Merck Biopharma, MSD, Nippon Kayaku, Ono Pharmaceutical, Pfizer, Taiho, Takeda; Financial Interests, Institutional, Invited Speaker: Chugai Pharmaceutical, Ono. Y. Tsubata: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo Co. Ltd, AstraZeneca K.K., Chugai Pharmaceutical Co. Ltd.; Financial Interests, Institutional, Research Grant: Pfizer Health Research Foundation. Y. Fujita: Financial Interests, Institutional, Research Grant: AstraZeneca. K.K, MSD K.K. H. Mizugaki: Financial Interests, Personal, Invited Speaker: Chugai Pharma, AstraZeneca, Nippon Boehringer Ingelheim. S. Yagishita: Financial Interests, Institutional, Research Grant: Nippon Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: LSI medience. A. Hamada: Financial Interests, Institutional, Research Grant: LSI Medience, Tosoh, Chugai, Eli Lilly and Company, Chordia Therapeutics, Cimic, Konica Minolta, Healios KK, Sysmex, Eisai. All other authors have declared no conflicts of interest.