Impact of Pre-treatment Proteinuria Progression on the Risk of Increased Proteinuria During Ramucirumab Therapy

Ramucirumab (RAM)-based treatment is often discontinued if proteinuria levels rise to 2+ or higher (≥2+) after treatment initiation. Several risk factors contributing to an increase in ≥2+ proteinuria during RAM-based treatment have been identified. However, the impact of pre-treatment changes on proteinuria fluctuations following RAM-based treatment initiation remains unclear.

This retrospective study included patients with gastric cancer who received RAM-based therapy following prior treatment with platinum-based chemotherapy at Gifu Prefectural General Medical Center between August 2015 and December 2021. Kaplan-Meier estimates were used to evaluate the incidence of ≥2+ proteinuria after initiating RAM-based treatment, based on the aggravating levels of proteinuria before initiating RAM-based treatment.

This study included 62 cases. The patients were divided into two groups: 14 with ≥2+ proteinuria after initiating RAM-based treatment (severe group) and 48 patients with <1 proteinuria (control group). The severe group had a higher proportion of patients presenting with trace proteinuria, i.e., proteinuria (+/-), at the start of RAM-based treatment. They also exhibited aggravating proteinuria within six months before initiating RAM-based treatment compared to the control group. The number of days until the onset of ≥2+ proteinuria was influenced by several factors, including proteinuria (+/-) at the start of RAM-based treatment, concurrent use of a calcium antagonist and aggravating proteinuria within six months before starting RAM-based treatment.

In addition to previously reported risk factors, aggravating proteinuria within six months before initiating RAM-based treatment appears to influence post-treatment proteinuria outcomes.