Abstract 32P
Background
Metastatic non-squamous non-small cell lung cancer is currently managed with pembrolizumab + pemetrexed + cisplatin/carboplatin, KEYNOTE189 regimen, as first-line chemotherapy. However, there are many people who are unable to continue chemotherapy due to renal dysfunction caused by pemetrexed.
Methods
We extracted data from the electronic medical records of 106 patients diagnosed with metastatic non-squamous non-small cell lung cancer who received the KEYNOTE 189 regimen at our institution between December 2018 and March 2024, and analyzed the data. Regarding renal function, we calculated creatinine clearance at three points: before treatment, at the start of maintenance therapy, and at the time of progressibe disease, and investigated the association with prognosis using the rate of change in creatinine clearance (ΔCcr). Regarding the dose of pemetrexed, we used the total dose of pemetrexed administered/the maximum planned dose of pemetrexed (pemetrexed administration ratio) to investigate trends in prognosis.
Results
At our institution, the ITT population for KEYNOTE 189 had mPFS of 8.3 mo (95% CI, 6.4–9.5) and mOS of 20.0 mo (95% CI, 14.4–26.94). Increasing the ΔCcr from the start of treatment to the time of PD tended to be associated with a poor prognosis, with the maximum HR of 2.53 (95% CI, 1.31–4.86) at a ΔCcr of 28.72. In addition, there was a trend towards worse prognosis as the pemetrexed administration ratio increased, with a maximum HR of 4.75 (95% CI, 2.45–9.22) at a pemetrexed administration ratio of 0.307.
Conclusions
The continuous administration of pemetrexed may cause renal dysfunction and shorten OS, and the pemetrexed administration ratio may be an indicator that very well reflects prognosis in an inverse proportion.
Legal entity responsible for the study
Department of Thoracic Oncology, Kansai Medical University Hospital.
Funding
Has not received any funding.
Disclosure
K. Murotani: Financial Interests, Personal, Other, Lecture fee: Chugai Pharmaceutical; Financial Interests, Personal, Other, Lecturer fee: AstraZeneca, Taiho pharmaceutical, MSD, Nihon Shinyaku; Financial Interests, Personal, Advisory Board: Pfizer. H. Yoshioka: Financial Interests, Personal, Invited Speaker, Lecture fee: Eli Lilly Japan K.K., Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Nippon Kayaku, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, MSD, AstraZeneca, Ono Pharmaceutical, Novartis Pharma, Kyowa Kirin, Otsuka Pharmaceutical, Amgen, Pfizer, Daiichi Sankyo, Nipro Pharma, Merck Biopharma; Financial Interests, Personal, Other, Consulting fee: Delta-Fly Pharma, Inc.; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Janssen Pharmaceutical, MSD, Novartis Pharma, Delta-Fly Pharma, Boehringer Ingelheim. T. Kurata: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Pfizer, Bristol Myers Squibb, Takeda, Eli Lilly, Chugai, Nipponkayaku, Ono; Financial Interests, Institutional, Invited Speaker: MSD, Takeda, Janssen, AstraZeneca, Daiichi Sankyo, Chugai, Amgen, Novartis, Ono. All other authors have declared no conflicts of interest.