Association between neutropenia and response to ramucirumab and paclitaxel in patients with metastatic gastric cancer.

The aim of this study was to evaluate if the occurrence of neutropenia is correlated with response to ramucirumab plus paclitaxel for metastatic gastric cancer. This is a retrospective study of patients treated with ramucirumab plus paclitaxel. Fifty-three patients were evaluated. Among these, 10 patients (26.5%) developed grade ≥3 neutropenia. Patients with grade ≥3 neutropenia reported a progression-free survival of 6.6 months (95% confidence interval 3.3-8.4) and overall survival of 11 months (95% confidence interval 5.9-13.1) vs. 4.4 months (95% confidence interval 3.9-5.2) and 8.7 months (95% confidence interval 7.8-10.1) respectively in patients' group with lower grade events. Our analysis seems to suggest that the occurrence of neutropenia predicts response to treatment with ramucirumab and paclitaxel.

The influence of prior ramucirumab treatment on the clinical activity of FOLFIRI as third-line therapy in patients with metastatic gastric Cancer.

Purpose Few data described the activity of chemotherapy after ramucirumab plus paclitaxel progression in metastatic gastric cancer patients. The aim of this phase II study is to assess the efficacy and safety of the FOLFIRI regimen as a third-line of treatment. Methods The study enrolled patients with histologically proven metastatic gastric cancer or gastroesophageal junction carcinoma whose disease had progressed after ramucirumab-based second line of treatment. Treatment consisted of biweekly irinotecan 150 mg/m2 as a 1-h infusion on day 1, folinic acid 100 mg/m2 intravenously on days 1-2, and 5-fluorouracil as a 400 mg/m2 bolus and then 600 mg/m2 continuous infusion over 22 h on days 1-2. Primary end-point was tumor response rate (confirmed complete and partial response). Results Twenty-six patients were enrolled. Overall response rate and disease control rate were 11.5% and 38.5%. The median progression free survival (PFS) was 52 days (95% CI:42-74), and the median overall survival was 117 days (95% CI: 94-154). no unexpected adverse events have been observed. A longer PFS and OS were observed in patients who had achieved PFS ≥ 3 months during prior ramucirumab treatment. Conclusions Our findings suggest a poor efficacy of the FOLFIRI regimen in metastatic gastric or gastroesophageal junction cancer patients whose disease progressed during a ramucirumab-based second line of treatment. However, FOLFIRI could be an option for patients who responded to prior ramucirumab.

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

PURPOSE: Hypertension (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. METHODS: Treatment 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. RESULTS: Thirty-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). CONCLUSIONS: Despite 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.

Safety and Efficacy of Cabozantinib in Metastatic Renal-Cell Carcinoma: Real-World Data From an Italian Managed Access Program.

BACKGROUND: The randomized phase 3 METEOR study confirmed a survival benefit of cabozantinib over everolimus in patients with metastatic renal-cell carcinoma (mRCC) with disease that progressed after treatment with at least one previous antiangiogenic inhibitor. The aim of this analysis was to evaluate the safety and activity of cabozantinib in an unselected population. METHODS: Data were collected across 24 Italian centers. Cabozantinib therapy was initiated at physician request between September and December 2016. Patients with mRCC with disease that progressed after one or more prior systemic treatment were evaluated. Cabozantinib 60 mg was administered orally once daily. Doses were reduced to 40 mg or 20 mg in patients experiencing grade 3 or intolerable grade 2 adverse events (AEs). RESULTS: Data from 96 patients were evaluated. Cabozantinib was administered as second-line therapy in 28 patients (29%) and as third-line therapy in 18 patients (19%), while the remaining 50 patients (52%) received cabozantinib in further treatment lines. Sixty-six patients began therapy with the full dose of 60 mg. Because of poor performance status, 29 patients began therapy with a reduced dose of 40 mg and 1 patient with 20 mg. At the time of our analysis, grade 3/4 AEs were observed in 35 patients (36%). Only 5 patients discontinued treatment as a result of AEs. Partial response was observed in 35 patients (36%), whereas 33 (34%) had stable disease and 28 (30%) progressive disease. Median progression-free survival was 8.0 months. CONCLUSION: Cabozantinib showed acceptable tolerability and activity in a large unselected population treated according to everyday clinical practice.

Docetaxel, oxaliplatin, 5FU, and trastuzumab as first-line therapy in patients with human epidermal receptor 2-positive advanced gastric or gastroesophageal junction cancer: Preliminary results of a phase II study.

The aim of this study is to report first preliminary results of patients enrolled in a phase II study that will investigate the activity and safety of docetaxel, oxaliplatin, and 5-fluorouracil (DOF) in combination with trastuzumab in human epidermal receptor-2 (HER-2) positive patients with advanced gastric or gastroesophageal junction (GEJ) cancer.Treatment consisted of docetaxel 70 mg/m combined with oxaliplatin 130 mg/m on day 1, and continuous infusion 5-fluorouracil mg/m days 1-5 plus trastuzumab at the standard dose on day 1, every 3 weeks for a maximum of 8 cycles.Fifteen patients were enrolled. The overall response rate was 60%. The median progression-free survival was 9.2 months (95% confidence interval [CI], 4.4-10.1 months) and the median overall survival was 19.4 months (95% CI, 8.9-21.1 months). Grade 3 neutropenia was observed in 3 patients (20%).The DOF plus trastuzumab seems active in HER-2 positive advanced gastric or GEJ cancer, final results of the phase II study are awaited.

Targeting VEGFR-2 in Metastatic Gastric Cancer: Results From a Literature-Based Meta-Analysis.

Angiogenesis is a key process in cancer development. We performed a meta-analysis to assess the efficacy and safety of the novel VEGFR-2 inhibitors in patients with metastatic gastric and gastroesophageal junction cancer. A literature-based meta-analysis of randomized controlled trials (RCTs) was undertaken. The primary outcome was the overall survival. The pooled analysis from RCTs on anti-VEGFR-2 inhibitors revealed a significant increase in overall survival (hazard ratio for death: 0.69, 95% confidence interval: 0.55-0.87; p = .002). This study confirms the efficacy of novel anti-VEGFR-2 inhibitors. The future studies of these agents will evaluate alone and in combination with chemotherapy the early line of treatment along with the identification of proper predictive biomarker.

New molecular therapies in patients with advanced Hepatocellular Cancer in second line of treatment: Is a real defeat?: Results from a literature based meta-analysis of randomized trials.

Several new biological agents have been investigated as second line of treatment in advanced Hepatocellular Cancer (HCC). We performed a meta-analysis to assess the effect of targeted therapies in advanced HCC patients beyond the first line of treatment. A literature-based metaanalysis of randomized controlled trials was undertaken. The primary outcome was the overall survival. The secondary endpoints were the progression-free survival (PFS), the response rate (RR) and disease control rate (DCR) and the safety. Pooled analysis of targeted agents revealed a modest increase in overall survival compared with control arm (Hazard Ratio (HR)=0.93, 95%CI: 0.83-1.04; P=0.21). On the counterpart, all the secondary endpoints were in favoured to the targeted agents-based treatment (PFS: HR=0.68, 95% CI:0.56-0.83; P=0.0002; RR: 3.50,95% CI 1.81-6.76; P=0.0002, DCR: RR:1.19, 95% CI 1.06-1.32; P=0.002). To date, there is a clinical need of a more efficacious second line of therapy in treatment of the advanced HCC. This study showed some activity of the new targeted therapies in second line of treatment in advanced HCC.