Assessing population diversity in phase III trials of cancer drugs supporting Food and Drug Administration approval in solid tumors

Our study aimed to assess inequities in the clinical trial participation for the selected patient groups. We searched the Food and Drug Administration (FDA) database and extracted phase-III clinical trial data from MEDLINE for each approved drug by the FDA between January 1, 2006, and June 30, 2020. We analyzed the inclusion/exclusion criteria, participation according to gender, ethnic group, performance score, the positivity of HBV and HCV, and HIV, having comorbidities and brain metastasis. We compared the findings with that of the general population by retrieving data from the Surveillance, Epidemiology and End Results (SEER) database. We identified 142 phase III pivotal oncology trials that enrolled 105 397 patients. The proportion of female patients in trials was lower than their relative prevalence in the general population from SEER region (36% vs 49.6%, P < .001). The rates of black patients included were lower than their relative prevalence from SEER region (2.1% vs 9.8%, P < .001). 1.3% and 0.8% of patients had HBV and HCV infections, respectively. The patients' numbers with organ dysfunction were not established due to insufficient data from clinical trials. 1.6% of all patients had controlled brain metastasis. Black patients, women and patients with brain metastasis or with HBV and HCV were underrepresented. Our study underscores the importance of expanding the inclusion/exclusion criteria of pivotal oncology trials to be more representative of patients seen in clinical practice

Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population

Clinicopathological Characteristics and Oncological Outcomes of Non-urothelial Bladder Carcinomas: A Multicenter Study

Objective: The incidence of non-urothelial bladder cancers is very low, so our knowledge about their treatment protocols and prognosis is limited. We evaluated the clinicopathological characteristics of 26 patients in three different clinics and aimed to determine the prognostic factors affecting oncological outcomes

ABO blood group and the risk of breast cancer: Multicenter, case-control, observational study

1572 Background: The role of genetic factors in the development of cancer is widely accepted. ABO blood type is an inherited characteristic and previous studies have observed an association between ABO blood group and risk of certain malignancies, including pancreatic and gastric cancer. The data on the role of ABO blood group and Rh factor in breast cancer is inconclusive. Methods: All patients who had breast cancer (BC) and treated between 2000-2010 at the Departments of Medical Oncology of both Ankara and Hacettepe Universities (Ankara, Turkey) with defined ABO blood type and Rh factor were included in our retrospective reviews of tumor registry records. A group of volunteer healthy women donors of Turkish Red Crescent between 2004-2011 were identified as a control group, without any matching factors. The relationship of ABO blood types and Rh factor with various prognostic factors such as age at diagnosis, menopausal status, family history of breast cancer, and ER/PR/HER2 status were evaluated from 1740 BC patients. We compared the distributions of ABO blood types, Rh factors among 1740 patients and 204,553 healthy controls. Among BC patients, differences between each of aforementioned ABO blood groups and Rh factors with respect to various prognostic factors were explored, respectively. Results: Overall distributions of ABO blood groups as well as Rh factor were comparable between patients (44% A, 8% AB, 16% B, 32% O, 88% Rh+) and controls (41% A, 8% AB, 16% B, 35% O, 87% Rh+). However, there were statistically significant differences between patients and controls with respect to A vs. nonA (p=0.019) and marginal significance (p=0.051) for O vs. nonO. Among patients, there were statistically significant differences between A and nonA with respect to HER2 (p=0.0421), M stage (p=0.0447), T stage (p=0.0020). Only T stage (p=0.0337) were significantly different between O vs nonO. Grade (p=0.0227) and M stage (p=0.0107) were significantly different between Rh factors. Conclusions: In our study sample, ABO blood type was statistically significantly associated with breast cancer. Additional studies are necessary to determine the mechanisms by which ABO blood type may influence the risk of breast cancer

Risk factors for thrombosis risk in patients with cancer

Aim: To evaluate the factors associated with Deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) in cancer patients. Materials and Methods: A total of 237 cancer patients who underwent lower extremity venous Doppler Ultrasonography (USG) and/or pulmonary computed tomography angiography (PCTA) were included. Patients’ demographic characteristics; chemotherapy data; immobilization status; use of central venous catheter; histories of 4-day-long bed rest, surgery within the last 6 months, long anesthesia for at least 2 hours, smoking, patients’ laboratory tests, ABO blood group, PCTA and lower extremity Doppler USG results were retrospectively reviewed through the hospital information management system. Results: The median age was 62 (age range 25 to 89). Thrombosis was detected in 83 patients according to the results of venous Doppler USG and/or PCTA of those patients who underwent imaging. Immobilization status (p=0.019), history of surgery within the last 6 months (p=0.02), anesthesia more than 2 hours (p=0.012) and 4-day-long bed rest (p=0.03) were found to be significantly associated with related risk of thrombosis. Additionally, thrombosis was found more frequently in the non-O group (especially group B) than in O group (p:0.024). Conclusions: Besides well-known risk factors, blood group may be related with risk of thrombosis in the patients with the cancer diagnosis Keywords: ABO blood group, Cancer, Pulmonary thromboembolism, Deep vein thrombosi