The impacts on prognosis of the relationship between decline in renal function associated with pemetrexed and the ratio of pemetrexed administration.

Abstract

e20623 Background: The KEYNOTE 189 regimen of pembrolizumab + pemetrexed + cisplatin/carboplatin is currently being used as first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). However, there are many patients who cannot continue chemotherapy due to decreased renal function 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 facility between December 2018 and March 2024, and conducted an analysis. With regard to renal function, creatinine clearance was calculated at three points in time: before treatment, at the start of maintenance therapy, and at the time of disease progression, and the trend in prognosis was examined using the rate of change (ΔCcr). With regard to the dose of pemetrexed, the trend in prognosis was examined using the total amount of pemetrexed administered/the maximum scheduled dose of pemetrexed (the ratio of pemetrexed administered). Results: In our institution, the mPFS and mOS in the ITT population were 8.3 months (95% CI, 6.4-9.5) and 20.0 months (95% CI, 14.4-26.94), and there was no significant difference from the KEYNOTE189 study. ΔCcr from the start of treatment to the start of maintenance therapy tended to have the most impact on prognosis, and an increase in ΔCcr was associated with a poorer prognosis, with a maximum HR of 2.53 (95% CI, 1.31-4.86) when ΔCcr was 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. When the groups were divided into four using these two cutoff values, there was a statistically significant difference in OS in the group with a low-low ΔCcr- ratio of pemetrexed administered. Conclusions: Our study suggests that suppressing the decline in renal function during the induction chemotherapy period and then not administering pemetrexed may lead to the best survival outcomes. There is therefore a need for comparative studies to determine the necessity of pemetrexed maintenance therapy in the KEYNOTE189 regimen.