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.

Gemcitabine plus nab-paclitaxel followed by maintenance treatment with gemcitabine alone as first-line treatment for older adults with locally advanced or metastatic pancreatic cancer.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of the combination Gemcitabine (Gem) plus nab-Paclitaxel (NabP) (Gem/NabP), followed by maintenance Gem in older adults with locally advanced or metastatic pancreatic cancer (PC). MATERIALS AND METHODS: In this prospective observational study, the induction chemotherapy consisted of NabP 125 mg/m2 followed by Gem 1000 mg/m2 on days 1, 8, and 15 of a 4-week cycle. After a maximum of 3 cycles, patients without evidence of progressive disease (PD) were administered Gem 1000 mg/m2 weekly for 3 of 4 weeks as maintenance therapy until documentation of PD or unacceptable toxicity. The primary endpoint was six-month disease-control rate (DCR). RESULTS: Overall, 36 patients >70 years with metastatic or locally advanced PC were enrolled at participating Institutions. After completion of Gem/NabP, 18 (50%) patients achieved partial response, 13 (36%) had stable disease, and 5 (14%) had PD. Thirty-one patients (86%) received Gem monotherapy as maintenance treatment for a median of 3 cycles (range, 2-9 cycles). Six-month DCR was 61% (95% CI, 45-77), median PFS was 6.4 months (95% CI, 5.4-8.3), and median OS was 13.4 months (95% CI, 11.1-16.7). During Gem/NabP regimen, the most common grade 3 toxicity included neutropenia (22%), anemia (19%) and thrombocytopenia (8%). Grade 3 neuropathy was not observed. During Gem maintenance therapy, grade 3 hematological toxicity was described in 6 patients (19%). CONCLUSION: Gem/NabP followed by maintenance Gem appears to be safe and effective for older patients with locally advanced or metastatic PC.

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.

Are EGFR tyrosine kinase inhibitors effective in elderly patients with EGFR-mutated non-small cell lung cancer?

EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib changed dramatically the history of metastatic non-small cell lung cancer (NSCLC) harbouring EGFR mutations. However, not enough data are available on the efficacy of these targeted drugs in elderly patients. The aim of this study is to analyse the available clinical data evaluating the efficacy of anti-EGFR therapies in elderly patients with advanced NSCLC carrying EGFR mutations. A literature-based meta-analysis of the results of randomized clinical trials was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology meetings were searched. Progression-free survival (PFS), as a measure of the efficacy of treatment, was the primary outcome investigated. The pooled analysis revealed an overall significant improvement in PFS (HR = 0.44, 95% CI 0.28-0.69; p = 0.0004) with the use of EGFR TKIs in EGFR-mutated NSCLC. The data stratification per age subgroups showed that EGFR TKIs were more effective in prolonging PFS in elderly patients, with HR 0.39 (p = 0.008), in comparison with young patients (HR = 0.48; p = 0.04). The results of this study suggest that EGFR TKIs have a significant effect in slowing down diseases progression in elderly patients with advanced NSCLC, therefore representing a valid therapeutic option in this age group.

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.

Targeting the androgenic pathway in elderly patients with castration-resistant prostate cancer: A meta-analysis of randomized trials.

BACKGROUND: The novel hormonal drugs have recently entered in the armamentarium of therapies for treatment of metastatic castration-resistant prostate cancer (CRPC). First reports are available for their use in elderly men with CRPC. METHOD: A meta-analysis of randomized controlled trials (RCTs) has been performed. PubMed, the Cochrane Library, and American Society of Clinical Oncology (ASCO) University Meeting were searched for data on the use of new hormonal treatment in elderly patients with CRPC. RESULTS: Nine studies for a total of 3512 elderly patients were available for meta-analysis. Six studies reported outcomes of patients aged >75 years old while 2 studies reported on patients aged >70 years old. The pooled analysis of the androgen synthesis inhibitors revealed significantly increased overall survival (OS) due to antiandrogen agents compared with placebo or placebo and prednisone (hazard ratio (HR) for death: HR = 0.74, 95% CI: 0.67-0.82; P < 0.00001). Moreover, the new antiandrogenic therapy significantly improved the progression-free survival (HR = 0.45, 95% CI: 0.31-0.65; P < 0.0001). The incidence of any grade ≥3 adverse effect was only moderately higher during with the antiandrogenic therapy as compared to the control arms (response rate = 1.03, 95% CI: 0.88-1.20; P = 0.72). CONCLUSION: This study confirmed that agents targeting the androgen axis (i.e., enzalutamide, abiraterone) significantly prolonged OS in elderly men with CRPC.

Monoclonal antibodies-based treatment in gastric cancer: current status and future perspectives.

Gastric cancer (GC) is the second leading cause of cancer-related death, and despite having improved treatment modalities over the last decade, for most patients, only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and the related signaling pathways offers, from the clinical point of view, promising advances for selected groups of patients. In the past, targeted therapies have significantly impacted the treatment strategy of several common solid tumors such as breast, colorectal, and lung cancers. Unfortunately, translational and clinical research shows fewer encouraging targeted treatments with regards to the GC. To date, only two monoclonal antibodies (mAb), named trastuzumab and ramucirumab, are approved for the treatment of advanced GC, suggesting that in GC, maybe more than in other cancers, effective targeted therapy requires patient selection based on precise predictive molecular biomarkers. The aim of this review is to summarize the available data on the clinical advantages offered by the use of mAbs in the treatment of advanced/metastatic GC. Future perspective is also discussed.

Chemotherapy in the last 30 days of life of advanced cancer patients.

PURPOSE: Chemotherapy near the end of life is an issue frequently discussed nowadays, but literature is generally poor. We analyzed patients with cancer who received chemotherapy in their last month of life. METHODS: The study involved all patients treated in our oncological department between 2010 and 2012; our attention focused on patients receiving chemotherapy in their last month of life. The hematologic malignancies are excluded. RESULTS: During the covered period, 2164 pts received chemotherapy, 162 received chemotherapy in their last month of life (24.3 %). The median age of this subgroup was 67.8 years, and median Eastern Cooperative Oncology Group (ECOG) performance status was 2. One hundred and five patients (64.8 %) were males. All patients presented a metastatic disease. Causes of death are as follows: 64.8 % progressive disease, sudden death in 4.9 %, toxicity in 3.1 %, and not available in 27.2 %. CONCLUSIONS: Twenty-four percent of patients treated with chemotherapy received their last regimen within 1 month of death. Percentage is in line with existing results. It is commonly acknowledged that age, performance status, tumor sensitivity, survival prognosis, and comorbidities should be considered in every chemotherapy decision-making; nevertheless, some studies show that age is not a crucial factor. At present, individual clinician is the only predictor for continuing chemotherapy in the last 4 weeks of life. Although appropriateness criteria were applied, patients were submitted to chemotherapy within 1 month of life; we hope that development of simultaneous care could help in end-life decision-making.

Abiraterone in heavily pretreated patients with metastatic castrate-resistant prostate cancer.

The aim of this study was to evaluate the activity and tolerability of abiraterone acetate in patients with metastatic castrate-resistant prostate cancer treated previously with more than three lines of chemotherapy. Patients received 1 g of abiraterone acetate (administered as four 250 mg tablets) orally once daily with prednisone at a dose of 5 mg orally twice daily. The primary endpoint was prostate-specific antigen (PSA) response. From August 2011 to January 2013, 36 patients were enrolled. PSA response was observed in 22 patients (61.1%, 95% confidence interval: 0.41-0.81). The median time to PSA progression was 7.3 months and after a median follow-up of 10.1 months, all patients were alive. The treatment was generally well tolerated; side effects secondary to mineralocorticoid excess resulting from blockade of CYP17 were largely controlled with prednisone. Abiraterone acetate seems to be an effective and well-tolerated treatment option for patients with metastatic castrate-resistant prostate cancer irrespective of the number of chemotherapy lines administered previously.