Introduction: Approximately 20–33% of all cancer patients are treated with acid-reducing agents (ARAs), most commonly proton pump inhibitors (PPIs), to reduce gastroesophageal reflux disease symptoms. Palbociclib and ribociclib are weak bases so their solubility depends on different pH. The solubility of palbociclib dramatically decreases to < 0.5 mg/ml when pH is above 4,5 but ribociclibs’ solubility decreases when pH increases above 6,5. In the current study, we aimed to investigate the effects of concurrent PPIs on palbociclib and ribociclib efficacy in terms of progression-free survival in metastatic breast cancer (mBC) patients. Patients and methods: We enrolled hormone receptor-positive, HER2-negative mBC patients treated with endocrine treatment (letrozole or fulvestrant) combined palbociclib or ribociclib alone or with PPI accompanying our observational study. During palbociclib/ribociclib therapy, patients should be treated with "concurrent PPIs" defined as all or more than half of treatment with palbociclib/ribociclib, If no PPI was applied, it was defined as ‘no concurrent PPI’, those who used PPI but less than half were excluded from the study. All data was collected from real-life retrospectively. Results: Our study included 217 patients, 105 of whom received palbociclib and 112 received ribociclib treatment. In the study population CDK inhibitor treatment was added to fulvestrant 102 patients ( 47%), to letrozole 115 patients (53%). In the Palbociclib arm fulvestrant/letrozole ratio was 53.3/46.7%, in the ribociclib arm it was 41.07/58.93%. Of 105 patients who received palbociclib, 65 were on concomitant PPI therapy, 40 were not. Of the 112 patients who received ribociclib, 61 were on concomitant PPI therapy, 51 were not. In the palbociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (13.04 months vs. unreachable, p < 0.001). It was determined that taking PPIs was an independent predictor of shortening PFS (p < 0.001) in the multivariate analysis, In the ribociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (12.64 months vs. unreachable, p = 0.003). It was determined that taking PPIs was single statistically independent predictor of shortening PFS (p = 0.003, univariate analysis). Conclusions: Our study demonstrated that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. If it needs to be used, PPI selection should be made carefully and low-strength PPI or other ARAs (eg H2 antagonists, antacids) should be preferred.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-po...

Analysis of PTEN, VEGF, HER2 and P53 Status in Determining Colorectal Cancer Benefit from Bevacizumab Therapy Bevacizumab;VEGF;PTEN;HER2-neu;p53;colorectal cancer; Background: No factor has thus far been identified to predict the efficacy of bevacizumab therapy for colorectal cancer. We here therefore studied PTEN, VEGF, HER2 and p53 by immunohistochemistry as possible prognostic and predictive factors. Materials and Methods: A total of 34 retrospectively collected tumor samples were evaluated, all from patients receiving bevacizumab-based regimens. VEGF-A, PTEN, HER2, p53 were assessed and data was compared with clinicopathologic characteristics of patients and the bevacizumab response rate. Results: In this study, the median age of the 34 metastatic colorectal cancer patients was 55.5 (24-75), twelve (35.3%) being women and 22 (64.7%) men. PTEN, VEGF, HER2, p53 expressions were compared with bevacizumab response and other chacteristics of disease. Statistical significant differences were not found between bevacizumab response rates and different expression levels of VEGF, PTEN, HER2 and p53 (respectively p=0.256, p=0.832, p=0.189, p=0.131). However, a survival difference was noted in the VEGF expression negative group (median OS:55 months; 95%CI, 22-88 months) (p=0.01). There was no statistically significant OS difference in other groups (PTEN p=0.6, HER2 p=0.189, p53 p=0.13). Conclusions: We did not find any predictive factor for BV therapy in our study. VEGF negative expression could be an important prognostic factor in metastatic colorectal carcinoma.

Background and Objectives: The systemic immune-inflammation index (SII), derived from peripheral blood parameters, has emerged as a novel marker reflecting the balance between host immunity and tumor-related inflammatory burden. This study aimed to investigate the prognostic impact of baseline SII on survival outcomes in patients with gastric or gastroesophageal junction (GEJ) cancer undergoing perioperative FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy. Materials and Methods: In this retrospective study, 168 patients with histologically confirmed gastric or GEJ cancer who received perioperative FLOT therapy were included. SII was calculated using the formula: SII = (Platelets × Neutrophils)/Lymphocytes. ROC curve analysis determined the optimal SII cutoff for predicting mortality. Patients were categorized into low (SII ≤685) and high (SII >685) groups. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan–Meier analysis and compared via the log-rank test. Cox proportional hazards regression models were used for univariate and multivariate analysis. Results: The optimal cutoff value for SII was determined to be 685 (AUC: 0.652, 95% CI: 0.558–0.747, p = 0.003). High SII was significantly shorter OS (17.4 vs. 28.2 months, p = 0.001) Multivariate analysis identified high SII (HR = 1.88, 95% CI: 1.36–2.89, p = 0.039), advanced T stage (HR = 3.693, p < 0.001), poor treatment response (HR = 0.36, p < 0.001), and ECOG-PS ≥1 (HR = 3.297, p < 0.001) as independent predictors of mortality. Conclusions: Elevated baseline SII is an independent predictor of worse OS and DFS in gastric and GEJ cancer patients receiving perioperative FLOT chemotherapy. SII may serve as a practical and inexpensive biomarker to support risk stratification and personalized treatment decisions.