Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer.

Background: Patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. Nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies of MSI-H or dMMR metastatic colorectal cancer.

Methods: In this phase 3 open-label trial, we randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive, in a 2:2:1 ratio, nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies.

Nivolumab plus chemotherapy or ipilimumab versus chemotherapy in patients with advanced esophageal squamous cell carcinoma (CheckMate 648): 29-month follow-up from a randomized, open-label, phase III trial.

Background: First-line nivolumab plus chemotherapy and nivolumab plus ipilimumab both demonstrated significant overall survival (OS) benefit versus chemotherapy in previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate 648 trial, leading to approvals of both nivolumab-containing regimens in many countries. We report longer-term follow-up data.

Methods: This open-label, phase III trial (NCT03143153) enrolled adults with previously untreated, unresectable, advanced, recurrent, or metastatic ESCC.

A Prospective Cohort Study of Biomarkers in Squamous Cell Carcinoma of the Anal Canal (SCCAC) and their Influence on Treatment Outcomes.

Although Chemoradiation (CRT) is the curative treatment for SCCAC, many patients present primary resistance. Since it is a rare tumor, response predictors remain unknown. We performed a prospective cohort study to evaluate biomarkers associated with CRT response, progression-free survival (PFS), and overall survival (OS).

Efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma.

Objectives: To evaluate the efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma (HCC).

Methods: We analyzed data from a cohort of patients with advanced HCC treated using systemic treatment according to the local institutional protocol. Patients were divided into two groups, Group A, individuals <70 years of age, and Group B, individuals 70 years of age or older at the time of treatment initiation.

Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial.

Importance: Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need.

Objective: To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater.

Design, Setting, And Participants: The phase 3 KEYNOTE-062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1 CPS of 1 or greater from 200 centers in 29 countries between September 18, 2015, and May 26, 2017.

Pembrolizumab for metastatic adrenocortical carcinoma with high mutational burden: Two case reports.

Rationale: In the setting of metastatic or locally advanced adrenocortical carcinoma, a limited number of therapies are available and their efficacy is generally below modest. The backbone of treatment remains surgery, even for metastatic disease, whenever it is possible, and mitotane. Chemotherapy can be used with limited results.

Expression of ERCC1, Bcl-2, Lin28a, and Ki-67 as biomarkers of response to first-line platinum-based chemotherapy in patients with high-grade extrapulmonary neuroendocrine carcinomas or small cell lung cancer.

Background: Small cell lung cancer (SCLC) and high-grade extrapulmonary neuroendocrine carcinomas (EPNEC) share similar histopathological features and treatment, but outcomes may differ. We evaluated in our study the expression of biomarkers associated with response rate (RR) to chemotherapy and overall survival (OS) for these entities.

Materials And Methods: This is a multicentre retrospective analysis of advanced EPNEC and SCLC patients treated with platinum-based chemotherapy.

Combination of Irinotecan, Oxaliplatin and 5-Fluorouracil as a Rechallenge Regimen for Heavily Pretreated Metastatic Colorectal Cancer Patients.

Purpose: Our objective was to evaluate the benefit of re-exposing patients with refractory metastatic colorectal cancer (mCRC) to a combination of oxaliplatin, irinotecan and 5-fluorouracil treatment.

Methods: We retrospectively analysed patients with mCRC who received a combination of oxaliplatin, irinotecan and fluorouracil as a rechallenge regimen after progressing on the same drugs. Both FOLFOXIRI and FOLFIRINOX were used.

Rivaroxaban: An Affordable and Effective Alternative in Cancer-Related Thrombosis?

Background: Venous thromboembolic events (VTEs) are common and potentially fatal complications in cancer patients, and they are responsible for the second most common cause of death. Low molecular weight heparin (LMWH) is the gold-standard treatment, but the costs involved limit its use, especially in developing countries. Recently, the oral anticoagulant rivaroxaban, which directly inhibits factor Xa, was approved for VTE treatment.

Clinical Features and Outcomes of Patients with Colorectal Cancers Harboring NRAS Mutations.

mutations are now routinely included in RAS testing prior to EGFR inhibitor therapy for metastatic colorectal cancer (mCRC). The clinical implications of mutation beyond lack of response to anti-EGFR therapy, however, are not known. We undertook this study to determine the clinical features and treatment outcomes of patients with -mutant mCRC.

The Rising Incidence of Younger Patients With Colorectal Cancer: Questions About Screening, Biology, and Treatment.

Colorectal cancer (CRC) is the third leading cancer diagnosed globally and an important cause of cancer-related mortality. Of interest, while we have witnessed a declining incidence trend over the past few decades in the older population, incidence rates for adolescents and young adults have been increasing steadily. Several factors may well explain this apparent epidemic in the young, namely a lack of routine screening and emerging lifestyle issues such as obesity, lack of exercise, and dietary factors.

Current Progress in Human Epidermal Growth Factor Receptor 2 Targeted Therapies in Esophagogastric Cancer.

Esophagogastric cancer is a worldwide health problem. The addition of the epidermal growth factor receptor 2 (HER2)-directed antibody trastuzumab to chemotherapy increased the overall survival of patients with metastatic HER2-positive esophagogastric cancer. This article discusses the available data to support HER2 as validated biomarker and recently completed and ongoing clinical trials of HER2-directed agents in metastatic and localized disease.

Review on TAS-102 development and its use for metastatic colorectal cancer.

TAS-102 is the combination of trifluridine (TFT) with tipiracil (TPI) in a 1:0.5 molar ratio. TFT is a fluoropyrimidine that retains cytotoxic activity in 5-fluorouracil resistant cell lines.

Phase 2 Trial of Metformin Combined With 5-Fluorouracil in Patients With Refractory Metastatic Colorectal Cancer.

Background: Observational and preclinical studies have suggested that metformin has antitumor effects in solid tumors, including colorectal cancer (CRC). However, the effects of metformin in CRC have not been tested in clinical trials.

Patients And Methods: This was a single-center, single-arm phase 2 clinical trial where histologically confirmed CRC patients with measurable and progressing metastatic disease previously treated with 5-fluorouracil (5-FU), irinotecan, oxaliplatin, and an anti-epidermal growth factor receptor (if the tumor was RAS wild type) were enrolled to receive metformin 850 mg orally continuously 2 times a day plus 5-FU 425 mg/m and leucovorin 50 mg intravenously weekly until disease progression, unacceptable toxicity, or withdrawal of consent.

Phase II trial of metformin and paclitaxel for patients with gemcitabine-refractory advanced adenocarcinoma of the pancreas.

Background: In patients with adenocarcinoma of the pancreas, there are no standard second-line regimens. Many pre-clinical studies have shown that metformin alone or when combined with paclitaxel has antitumour effects on this tumour. We have tested here the combination of paclitaxel and metformin for patients with gemcitabine-refractory pancreatic cancer.

Primary prevention of colorectal cancer: myth or reality?

Colorectal cancer incidence has been rising strongly in parallel with economic development. In the past few decades, much has been learned about the lifestyle, dietary and medication risk factors for this malignancy. With respect to lifestyle, compelling evidence indicates that prevention of weight gain and maintenance of a reasonable level of physical activity can positively influence in lowering the risk.

Is surgery always necessary in rectal cancer?

Rectal cancer is a major health problem around the world, representing about one-third of the total colorectal cancer cases. Because of its anatomical location, there is a higher risk of local recurrence, and treatment often requires a complex multidisciplinary approach which includes neoadjuvant radiotherapy, chemotherapy, and a radical surgical procedure that commonly leads to a permanent colostomy. The cure rate with this strategy is good, with some patients having no residual disease in the surgical specimen.

ERCC1 in advanced biliary tract cancer patients treated with chemotherapy: prognostic and predictive roles.

Background: In oncology, we tend to look for factors that reflect better prognosis or predict response to treatments in order to make a selection from which patients will derive the benefit, avoiding futile therapies and/or toxicities. Definitive prognostic and predictive factors in advanced biliary cancer remain unknown.

Methods: We retrospectively analyzed all consecutive patients in our institution with advanced biliary tract cancer treated with palliative cisplatin plus gemcitabine.

Combination of irinotecan and a platinum agent for poorly differentiated neuroendocrine carcinomas.

Extrapulmonary poorly differentiated neuroendocrine carcinoma (PDNEC) is a rare and highly aggressive neoplasm for which the optimal chemotherapy remains unclear. The objective of this study was to evaluate the outcomes of patients with PDNEC treated with cisplatin and irinotecan (IP) and perform a review of the literature. From 2008 to 2012, patients with advanced PDNEC (Ki67≥20%) who received the IP combination were selected for analysis.

Bevacizumab: overview of the literature.

Inhibiting the angiogenic process is a clever method of cancer care. Over the last decade, some antiangiogenic compounds have been developed and approved for cancer treatment. Bevacizumab is a humanized monoclonal antibody that inhibits VEGF activity.