Safety Of Ramucirumab In Patients Research Articles

The Efficacy and Safety of Ramucirumab in Heavily Pretreated Advanced Hepatocellular Carcinoma.

Ramucirumab has been approved for the management of hepatocellular carcinoma (HCC) after progression on sorafenib; however, the data on ramucirumab in heavily pretreated HCC are limited. This study aimed to investigate the real-world efficacy and safety of ramucirumab in patients with heavily pretreated advanced HCC. Patients with advanced HCC who received intravenous ramucirumab as second-line and later therapy were retrospectively reviewed. Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). Additionally, prognostic factors were estimated using hazard ratios with 95% confidence intervals. In total, 31 patients with advanced HCC who received ramucirumab were enrolled, including 11 patients with second-line treatment and 20 with third-line and later-line treatment. The objective response rate was 3.2% with a disease control rate (DCR) of 45.2%, and the DCR of ramucirumab between the second-line group and the third-line and later-line groups did not differ. The median PFS and OS were 2.1 months and 6.7 months, respectively, in the whole population. In the multivariate analyses, alpha-fetoprotein <1,000 ng/ml was an independent prognostic factor for better PFS and OS. All adverse events were classified as grade 1-2 without grade 3-4 toxicities or drug-related mortality. Additionally, 51.6% of patients received subsequent therapy after progression on ramucirumab. The results of our study show the efficacy and safety of ramucirumab in patients with heavily pretreated HCC in real-world practice.

Safety of ramucirumab in patients with advanced gastric cancer in Europe and North America: A prospective observational registry.

341 Background: The objective was to describe the safety of ramucirumab (Ram) for previously treated advanced gastric cancer under real-world conditions in Europe and North America. Methods: This was a non-interventional, descriptive study of adult patients with advanced gastric or gastroesophageal junction adenocarcinoma whose disease had progressed after first-line chemotherapy (I4T-MC-JVDD). Data collection began in December 2015 and was completed in August 2021. Patients were followed up to 12 months after initiation of Ram. Safety outcomes included adverse events (AEs)/serious AEs (SAEs), and AEs leading to dose adjustment or death. Subgroups of interest were elderly, patients with cardiac comorbidities, hepatic, or renal impairment. Results: 606 patients were classified in 3 cohorts: Ram monotherapy (Ram Mono, N=51); Ram plus paclitaxel (Ram+PTX, N=547); or Ram plus other anti-cancer agents (N=8). Most patients were male (70%), white (97%) and aged ≥65 (55%); 22% of the population was ≥75 years old. Metastatic cancer was reported in 552 patients (96%); primary tumor location was gastric in 417 patients (69%) and in the gastroesophageal junction in 189 patients (31%). Patients were previously treated mainly with platinum (97%) and fluoropyrimidine (96%). Hypertension was the most frequently reported historical medical condition (25%). At baseline, 23% patients had documented cardiac comorbidities, 11% hepatic impairment and 6% renal impairment. The median duration of Ram was 8 weeks (IQR=4.0-10.6) in Ram Mono and 15 weeks (IQR=8.4-26.7) in Ram+PTX. Regardless of causality, 98% of patients experienced ≥1 AE; most commonly fatigue (31%) and abdominal pain (20%) in Ram Mono cohort; and fatigue (46%) and neuropathy (31%) in Ram+PTX cohort. In total, 40% experienced ≥1 AE of special interest; most commonly bleeding/hemorrhage (21% [mainly epistaxis]) and hypertension (11%). In total, 33 patients (5%) died due to AEs that occurred on, or within 90 days of last dose of Ram, 9 (2%) were related to Ram treatment as per physician’s assessment. Conclusions: The observed safety profile of Ram in the real-world setting was manageable and consistent with the established safety profile of Ram identified from clinical trials. No new safety concerns or notable findings were observed overall or in the subgroups of interest. Clinical trial information: ENCEPP/SDPP/9400 . [Table: see text]

Efficacy and Safety of Ramucirumab in Patients with Unresectable Hepatocellular Carcinoma with Progression after Treatment with Lenvatinib.

Objective A survival benefit was demonstrated for ramucirumab (RAM) in patients with unresectable hepatocellular carcinoma (uHCC) and α-fetoprotein (AFP) concentrations ≥400 ng/mL who had previously received sorafenib (SOR). However, it is unclear whether RAM has a similar efficacy in patients with uHCC that progresses after lenvatinib (LEN) treatment. This study aimed to evaluate the early anti-tumor response to RAM as a second-line treatment for advanced uHCC after LEN treatment. Methods We retrospectively assessed the efficacy and safety of RAM at 6 weeks after initiation. The therapeutic effects were evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Patients We evaluated 7 patients with uHCC who received RAM as a second- or third-line treatment after LEN failure. Results The disease control rate (DCR) was 28.6% (2 of 7 patients). After the initiation of RAM, a rapid disease progression resulted in 1 patient death after 19 days. The median progression-free survival (PFS) was 41 days. There were no grade 3 or 4 treatment-related adverse events. At 6 weeks, there was no deterioration in the modified albumin-bilirubin (mALBI) grade. In patients with an imaging response of stable disease (SD), the rate of AFP production decreased from the baseline. Conclusion RAM may have a therapeutic potential for the suppression of uHCC progression in patients previously treated with LEN, as well as for maintaining the liver function during treatment. Evaluating the AFP trends may therefore be useful for predicting RAM effectiveness.

Ramucirumab and Paclitaxel in Patients with Gastric Cancer and Prior Trastuzumab: Subgroup Analysis from RAINBOW Study

Aim: This subgroup analysis of the RAINBOW study evaluated the efficacy and safety of ramucirumab in patients with gastric cancer/gastroesophageal junction adenocarcinoma who received prior trastuzumab therapy. Patients & methods: Of adult patients enrolled in the RAINBOW study, 39 had received prior trastuzumab therapy. Of these, 20 patients were treated with ramucirumab plus paclitaxel and 19 patients with placebo plus paclitaxel within the RAINBOW trial. Results: Overall survival was longer with ramucirumab plus paclitaxel (11.4 months; 95% CI: 7.0-17.9) versus placebo plus paclitaxel (7.0 months; 95% CI: 3.4-14.6), hazard ratio: 0.68 (0.33-1.41); p=0.30. Longer progression-free survival, higher objective response were observed in ramucirumab combination group. Conclusion: Ramucirumab plus paclitaxel demonstrated efficacy benefits with manageable safety profile in a subgroup of patients pretreated with trastuzumab. Clinical trial registration number: NCT01170663.

A phase 2, single‐arm study of ramucirumab in patients with metastatic renal cell carcinoma with disease progression on or intolerance to tyrosine kinase inhibitor therapy

Multitargeted tyrosine kinase inhibitors (TKIs) have antitumor activity in metastatic renal cell carcinoma (mRCC). Resistance to these agents develops frequently, and their use is often limited by intolerance. Ramucirumab is a recombinant human monoclonal antibody directed against human vascular endothelial growth factor receptor-2. For this study, the authors investigated the clinical efficacy and safety of ramucirumab in patients with TKI-resistant/intolerant mRCC. In this single-arm phase 2 trial, patients received ramucirumab 8 mg/kg every 2 weeks until they developed disease progression or intolerable toxicity. The primary endpoint was the best objective response rate (ORR); additional endpoints included the disease control rate (DCR), progression-free survival (PFS), the median duration of overall response, and safety. Thirty-nine patients with RCC received ramucirumab monotherapy. Prior TKI therapy included sunitinib (59% of patients), sunitinib and sorafenib (30.8% of patients), and sorafenib (10.3% of patients). The ORR was 5.1% (95% confidence interval [CI], 0.6%-17.3%). The 12-week DCR was 64.1% (95% CI, 47.2%-78.8%). The median PFS was 7.1 months (95% CI, 4.1-9.7 months), and the median overall survival was 24.8 months (95% CI, 18.9-32.6 months). Grade 3 or higher adverse events that occurred in ≥5% of patients included grade 3 hypertension (7.7%) and proteinuria (5.1%). There was 1 on-study death from multiorgan failure. Although the study did not meet its primary endpoint of ≥15% ORR, ramucirumab was associated with evidence of antitumor activity in patients with TKI-resistant/intolerant mRCC. Ramucirumab was safe and well tolerated.