Phase II clinical trial of nab-paclitaxel plus gemcitabine in elderly patients with previously untreated locally advanced or metastatic pancreatic adenocarcinoma: the BIBABRAX study.

PURPOSE: To evaluate the health-related quality of life (HRQoL), global health status (GHS), and deterioration-free survival of an elderly population (> 70 years) with unresectable locally advanced (LAPC) or metastatic pancreatic cancer (mPC) treated with nab-paclitaxel in combination with gemcitabine. METHODS: In this open-label, single-arm, multicenter, phase II trial, patients received 4-week cycles of intravenous (i.v.) nab-paclitaxel at a dose of 125 mg/m2, followed by i.v. injections of gemcitabine at a dose of 1000 mg/m2 on days 1, 8 and 15 until disease progression or unacceptable toxicity was observed. The primary outcome was the HRQoL (deterioration-free rate at 3 months as evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. RESULTS: Eighty patients (median age: 74.6 years) were enrolled (56 with mPC, 24 with LAPC). The percentage of patients who had not experienced deterioration at 3 months was 54.3% (95% CI 41.6-67.0%). The median (interquartile range) time until definite deterioration was 1.6 (1.1-3.7) months. The objective response rate and clinical benefit rate were achieved by 11 (13.8%, 95% CI 6.2-21.3%) and 54 patients (67.5%, 95% CI 57.2-77.8%), respectively. The median overall survival was 9.2 months (95% CI 6.9-11.5), and the median progression-free survival was 7.2 months (95% CI 5.8-8.5). Only fatigue and neutropenia demonstrated a grade 3-4 toxicity incidence > 20%. CONCLUSIONS: Our study confirms the clinical benefit of the combination of nab-paclitaxel and gemcitabine in an elderly population with pancreatic cancer in terms of improved survival and clinical response. However, we were unable to confirm a benefit in terms of quality-of-life.

A systemic inflammation response index (SIRI) correlates with survival and predicts oncological outcome for mFOLFIRINOX therapy in metastatic pancreatic cancer.

OBJECTIVES: Systemic inflammatory response and survival has not been evaluated as a predictive factor of chemotherapy in metastatic pancreatic cancer. The aim of this study was to evaluate the prognostic and predictive value of a baseline Systemic Inflammation Response Index (SIRI) in metastatic pancreatic cancer. METHODS: Retrospective study of 164 metastatic pancreatic cancer patients. Associations between overall survival (OS), progression free survival (PFS), chemotherapy and SIRI were analyzed. SIRI is defined by neutrophil x monocyte/lymphocyte 109/L. RESULTS: Median age 66 years. 22 (13%) received mFOLFIRINOX, 59 (36%) gemcitabine + nab-paclitaxel, 40 (24%) gemcitabine, 13 (8%) other regimens and 30 (18%) had not received treatment. Patients with SIRI<2.3 × 109/L showed a statistically significant improvement in OS compared to SIRI≥2.3 × 109/L [16 months versus 4.8 months, Hazard Ratio (HR) 2.87, Confidence Interval (CI) 95% 2.02-4.07, p < 0.0001] that was confirmed in multivariate analysis. In addition, patients with SIRI<2.3 × 109 showed a longer PFS (12 versus 6 months, HR 1.92, IC 95% 1.314-2.800, P = 0.001). Furthermore, we observed that patients with SIRI ≥2.3 × 109/L were more likely to benefit from mFOLFIRINOX therapy. Patients with an elevated SIRI treated with mFOLFIRINOX versus gemcitabine plus nab-paclitaxel and gemcitabine showed a clinically and statistically significant difference in median OS of 17 months compared to 6 and 4 months respectively (p < 0.001). Conversely, the difference was not clinically significant in the SIRI<2.3 × 109/L subgroup: 15.9 months versus 16.5 and 16, respectively. CONCLUSION: An elevated SIRI (≥2.3 × 109/L) was an independent prognostic factor for patients with metastatic pancreatic cancer, warranting prospective evaluation.

Bevacizumab in Combination with Capecitabine plus Irinotecan as First-Line Therapy in Metastatic Colorectal Cancer: A Pooled Analysis of 2 Phase II Trials.

BACKGROUND: Although phase III studies have investigated the effect of adding bevacizumab to the 3-weekly capecitabine plus irinotecan (XELIRI) combination in the first-line treatment of metastatic colorectal cancer (mCRC), no phase III studies investigating the effects of adding bevacizumab to biweekly XELIRI have been published. PATIENTS AND METHODS: A retrospective pooled analysis of 2 single-arm phase II studies was performed. Previously untreated patients with mCRC received irinotecan 175 mg/m(2) on day 1 followed by capecitabine 1,000 mg/m(2) twice daily on days 2-8 every 2 weeks with or without bevacizumab 5 mg/kg on day 1. RESULTS: In total, 53 patients received XELIRI, and 46 patients received XELIRI plus bevacizumab. There was a statistically significant increase in partial response rate with XELIRI plus bevacizumab (63 vs. 26% for XELIRI; p = 0.0002) and overall response rate (67 vs. 32%; p = 0.0005). Median time to disease progression was significantly longer with XELIRI plus bevacizumab (12.3 vs. 9.0 months for XELIRI; p = 0.012); median overall survival did not differ significantly between treatments (23.7 vs. 19.3 months; p = 0.4997). The proportion of patients experiencing at least 1 grade 3/4 adverse event was similar with both treatments (XELIRI, 47%; XELIRI plus bevacizumab, 44%). CONCLUSION: This retrospective pooled analysis suggests that XELIRI plus bevacizumab has an acceptable tolerability profile and improves efficacy outcomes compared with XELIRI in the first-line treatment of mCRC.