Association between ramucirumab-related hypertension and response to treatment in patients with metastatic gastric cancer

Abstract

PurposeHypertension (HTN) is frequently associated with the use of angiogenesis inhibitors targeting the vascular endothelial growth factor pathway, such as ramucirumab. The aim of this study was to retrospectively evaluate if occurrence of HTN is correlated with response to second line treatment with ramucirumab+paclitaxel for metastatic gastric cancer.MethodsTreatment consisted of ramucirumab 8 mg/kg intravenously (iv) on days 1 and 15, plus paclitaxel 80 mg/m2 iv on days 1, 8, and 15 of a 28-day cycle. Patients received study treatment until disease progression, unacceptable toxicity, or withdrawal of consent.ResultsThirty-four patients were retrospectively evaluated. Among these, 6 (17.6%) developed grade 3 ramucirumab-induced HTN. These patients had a better outcome than those with lesser grades events, with a progression-free survival (PFS) of 7.8 months (95% CI 4.4-not reached) versus 4.2 months (95% CI 3.1-5.2) (p=0.001). overall survival (OS) was 11.9 months (95% CI 9.3-not reached) in the grade 3 HTN group, versus 7.2 months (95% CI 5.9-10.1).ConclusionsDespite the small number of patients and the retrospective nature of the data, our analysis showed that occurrence of ramucirumab-related HTN, in particular G3 HTN, predicts response to treatment with ramucirumab+paclitaxel in patients with metastatic gastric cancer.

Treatment sequences of patients with advanced colorectal cancer and use of second-line FOLFIRI with antiangiogenic drugs in Japan: A retrospective observational study using an administrative database

“…As quantitative proteinuria tests are often conducted as part of daily monitoring of patients treated with these drugs, this result might imply that adverse event monitoring for proteinuria during treatment is important with antiangiogenic drugs. Although hypertension has been reported to be associated with the effectiveness of bevacizumab in patients with CRC [ 39 ] and ramucirumab in patients with gastric cancer [ 40 , 41 ], this association is not unanimously accepted because it has not been reported in patients receiving ramucirumab treatment for CRC [ 42 ]. Because of the nature of retrospective studies, it is not possible to determine whether a causal relationship exists between longer overall treatment duration and proteinuria tests or antihypertensive prescriptions.…”

Therapeutic Inhibition of VEGF Signaling and Associated Nephrotoxicities

“…42 However, in patients receiving ramucirumab for gastric cancer, treatment-related hypertension was predictive of improved outcomes. 43,44 Importantly, Eremina et al reported that in a case series of six patients, bevacizumab use was associated with development of renal TMA. The patients had hypertension, proteinuria, and biopsy findings of glomerular endothelial cell injury (Table 3)-findings the investigators confirmed in a transgenic mouse model ( Table 1).…”

How May Ramucirumab Help Improve Treatment Outcome for Patients with Gastrointestinal Cancers?

“…The safety and effectiveness of ramucirumab as a treatment option for patients with GC/GEJ adenocarcinoma has also been examined in real world clinical practice in the Western world. For example, in the RAMIS study in Spain [ 68 ], the RAMOSS study in Italy [ 69 ], along with a few smaller studies [ 70 , 71 , 72 , 73 ], all indicated that ramucirumab is well tolerated in real life situations with similar survival outcomes and response rates as seen in the RCTs.…”