Real Life Data and Outcome of FOLFIRINOX Use in Metastatic Pancreatic Cancer Patients in General Hospitals in the Netherlands.

INTRODUCTION: Pancreatic cancer is one of the five most common causes of cancer mortality in developed countries. In patients with metastatic disease, the most frequent treatment used is FOLFIRINOX, which is associated with moderate toxicity which could influence quality of life. The efficacy of FOLFIRINOX in a general population in the Netherlands has not been subject of research before, and therefore, this research has been set up in order to investigate what the real-life benefits of FOLFIRINOX are in a population with metastatic pancreatic cancer (mPC) treated in three general hospitals in the Netherlands. METHODS: The data used in this study was collected by patient records leading to a noninterventional retrospective cohort study. Eighty-six patients, over 18 years of age, diagnosed with mPC between the years 2015 and 2022 and treated with FOLFIRINOX at Maasstad Hospital in Rotterdam, Amphia Hospital in Breda, or Catharina Hospital in Eindhoven, were included in the study. Kaplan-Meier models were used in order to represent survival outcomes. RESULTS: The results showed a median overall survival of 228 days (IQR 118-355). Only 14.0% (n = 12) completed the first-line treatment, and 51.2% (n = 44) of patients stopped treatment before or during cycle 6. Toxicity is highest, grade 3, after the first cycle but remains high for grade 1 and 2 during all treatment cycles. CONCLUSION: Survival rates for patient with metastatic pancreatic cancer treated with FOLFIRINOX were worse in our study population than in comparative studies.

The potential of RAS/RAF/MEK/ERK (MAPK) signaling pathway inhibitors in ovarian cancer: A systematic review and meta-analysis.

BACKGROUND: The RAS/RAF/MEK/ERK (MAPK) pathway plays a role in ovarian carcinogenesis. Low-grade serous ovarian carcinoma (LGSOC) frequently harbors activating MAPK mutations. MAPK inhibitors have been used in small subsets of ovarian carcinoma (OC) patients to control tumor growth. Therefore, we performed a meta-analysis to evaluate the effectiveness of MAPK inhibitors in OC patients. We aimed to determine the clinical benefit rate (CBR), the subgroup of MAPK inhibitors with the best CBR and overall response rate (ORR), and the most common adverse events. METHODS: We conducted a search in PubMed, Embase via Ovid, the Cochrane library and clinicaltrials.gov on studies evaluating the efficacy of single MAPK pathway inhibition with MAPK pathway inhibitors in OC patients. Our primary outcome included the CBR, defined by the proportion of patients with stable disease (SD), complete (CR) and partial response (PR). Secondary outcomes included the ORR (including PR and CR) and grade 3 and 4 adverse events. Meta-analysis was performed using a random-effects model. RESULTS: We included nine studies with a total of 319 OC patients, for which we determined a pooled CBR of 63% (95%-CI 39-84%, I2 = 92%). Combined treatment with Raf- and MEK inhibitors in in BRAFv600 mutated LGSOC (n = 6) had the greatest efficacy with a CBR of 100% and ORR of 83%. MEK inhibitors had the best efficacy as a single agent. Subgroup analysis by tumor histology demonstrated a significantly higher CBR and ORR in patients with LGSOC, with a pooled CBR and ORR of 87% (95%-CI 81-92%, I2 = 0%) and 27% (95%-CI 10-48%, I2 = 77%) respectively. Adverse events of grade 3 or higher were reported frequently: 123 in 167 patients. CONCLUSIONS: MEK inhibitors are the most promising single agents in (LGS)OC. However, dual MAPK pathway inhibition should be considered in patients with a BRAFv600 mutation, or non-mutated OC with depleted treatment options due indications of higher efficacy and tolerable toxicity profiles.