Systemic Therapy in Advanced Hepatocellular Carcinoma: Patient Selection and Key Considerations.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Most patients with HCC have advanced disease at initial diagnosis, and sorafenib has been the only systemic treatment option for more than a decade in patients with advanced, unresectable HCC. However, there has been a dramatic change in the treatment algorithm in the last several years, given new drug approvals in the field.

Time to first treatment is an independent prognostic factor for Multiple Myeloma (MM).

Introduction: Multiple myeloma (MM) is an incurable plasma cell neoplasm. In this study, we aimed to analyze the impact of time to initiation of systemic therapy for MM on overall survival (OS).

Methods: We identified cases diagnosed with MM from the National Cancer Database from 2004 to 2013.

First-Line Targeted Therapy for Hepatocellular Carcinoma: Role of Atezolizumab/Bevacizumab Combination.

Hepatocellular carcinoma (HCC) is an aggressive malignancy accounting for 90% of primary liver malignancies. Therapeutic options for HCC are primarily based on the baseline functional status, the extent of disease at presentation and the underlying liver function that is clinically evaluated by the Barcelona-Clinic Liver Cancer system and Child−Pugh score. In patients with advanced HCC, the United States Food and Drug Administration (US-FDA) approved systemic therapies include the combination of atezolizumab−bevacizumab, sorafenib, and lenvatinib in the first line setting while cabozantinib, regorafenib, ramucirumab (in patients with alfa-fetoprotein [AFP] > 400 ng/mL), pembrolizumab, nivolumab, and nivolumab-ipilimumab combination are reserved for patients who progressed on sorafenib.

Economic Cost and Sustainability of Oral Therapies in Precision Oncology.

Purpose: Precision oncology promises improved outcomes but the cost-effectiveness and accessibility of targeted therapies is debatable. We report price change patterns from 2015 to 2019 for several oral anticancer medications for common solid tumor malignancies.

Methods: We collected provider utilization and payment data from the public Medicare Part D database and extracted drug price information for commonly prescribed targeted oral anticancer agents for lung, breast, and prostate cancer.

Trials, Tribunals, and Opportunities for Lung Cancer KRASG12C Brain Metastases.

The activity of KRAS inhibitors against brain metastases is relatively unexplored. The recent work on preclinical models and preliminary data from the ongoing KRYSTAL-1 phase Ib clinical trial support the potential of adagrasib (MRTX849) to penetrate the central nervous system and provide control of KRASG12C brain metastases. See related article by Sabari et al.

Change in Patients' Perceived Cognition Following Chimeric Antigen Receptor T-Cell Therapy for Lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy can lead to durable responses in patients with relapsed/refractory hematologic malignancies. Immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) are common and may place patients at risk for longer-term cognitive impairment. This study examined changes in cognition in the first year after CD19-directed CAR T-cell therapy for lymphoma, as well as CAR T-cell therapy-specific risk-factors (e.

Change in Neurocognitive Performance Among Patients with Non-Hodgkin Lymphoma in the First Year after Chimeric Antigen Receptor T Cell Therapy.

The success of chimeric antigen receptor (CAR) T cell therapy in treating patients with relapsed/refractory hematologic malignancies is leading to a growing number of survivors treated with this regimen. To our knowledge, no previous studies have examined neurocognitive performance in adult CAR T cell therapy recipients, despite high rates of neurotoxicity and cytokine release syndrome (CRS) in the acute treatment period. This study examined changes in neurocognitive performance in the first year after CAR T cell therapy for non-Hodgkin lymphoma (NHL).

Alliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer.

This report describes the rationale, purpose and design of A011801 (CompassHER2 RD), an ongoing prospective, multicenter, Phase III randomized trial. Eligible patients in the United States (US) and Canada with high-risk (defined as ER-negative and/or node-positive) HER2-positive (HER2+) residual disease (RD) after a predefined course of neoadjuvant chemotherapy and HER2-directed treatment are randomized 1:1 to adjuvant T-DM1 and placebo, versus T-DM1 and tucatinib. Patients have also received adjuvant radiotherapy and/or endocrine therapy, if indicated per standard of care guidelines.

Management of well-differentiated neuroendocrine tumors.

Neuroendocrine tumors (NETs) are a heterogeneous group of epithelial neoplasms with predominantly neural and endocrine differentiation that have the ability to produce peptide hormones and other biologically active substances. The histologic characterization of NETs based on differentiation and grading is crucial to determining prognosis and treatment. Surgery still offers the best chance of cure for patients with NETs, and tumor resection is the preferred approach when possible.

FGFR Inhibitors in Oncology: Insight on the Management of Toxicities in Clinical Practice.

Fibroblast Growth Factor receptor (FGFR) pathway aberrations have been implicated in approximately 7% of the malignancies. As our knowledge of FGFR aberrations in cancer continues to evolve, FGFR inhibitors emerged as potential targeted therapeutic agents. The promising results of pemigatinib and infigratinib in advanced unresectable cholangiocarcinoma harboring fusions or rearrangement, and erdafitinib in metastatic urothelial carcinoma with and genetic aberrations, lead to their accelerated approval by the United States (USA) FDA.

Outcomes of COVID-19 in Patients With Cancer: A Closer Look at Pre-Emptive Routine Screening Strategies.

Purpose: The benefit of routine pre-emptive screening for severe acute respiratory syndrome coronavirus 2 infections in patients with cancer before cancer-directed therapies is unclear. Herein, we characterize the outcomes of a cohort of patients with cancer who were diagnosed with COVID-19 by routine screening (RS) in comparison with those diagnosed on the basis of clinical suspicion or exposure history (nonroutine screening [NRS]).

Methods: A multisite prospective observational study was conducted at three major and five satellite campuses of the Mayo Clinic Cancer Center between March 18 and July 31, 2020.

Aspirin and Statin Use and the Risk of Gallbladder Cancer.

Aspirin and statin drugs have been associated with reduced risk of several gastrointestinal cancers, but their association with gallbladder cancer (GBC) has not been well established. We evaluated the association of aspirin and statins with the risk of GBC. Patients with GBC managed at Mayo Clinic between 2000 and 2019 were matched 1:2 with a general patient pool by age and sex.

Quality of life in caregivers of patients receiving chimeric antigen receptor T-cell therapy.

Objective: Informal family caregivers provide critical support for patients receiving chimeric antigen receptor (CAR) T-cell therapy. However, caregivers' experiences are largely unstudied. This study examined quality of life (QOL; physical functioning, pain, fatigue, anxiety, and depression), caregiving burden, and treatment-related distress in caregivers in the first 6 months after CAR T-cell therapy, when caregivers were expected to be most involved in providing care.

Prevention and treatment of FGFR inhibitor-associated toxicities.

Fibroblast growth factor receptor (FGFR) inhibitors have shown promising results in terms of objective response rates in phase I/II trials in various malignancies that harbor FGFR genetic aberrations. The class of medications brings in the concept of 'personalized' treatment by targeting susceptible FGFR genetic alterations in some rare but dismal cancers such as cholangiocarcinoma. Despite the fact that FGFR inhibitors are well-tolerated, these drugs are associated with toxicities that are distinct from that of other small-molecule tyrosine kinase inhibitors.

Venous thromboembolism associated with CD19-directed CAR T-cell therapy in large B-cell lymphoma.

VTE developed in 11% of lymphoma patients after CAR T-cell therapy and was managed safely with anticoagulation. Coagulation abnormalities after CAR T-cell therapy occur but do not commonly lead to bleeding events.

Epigenetic modulation of immunotherapy cofactors to enhance tumor response in lung cancer.

Immunotherapy with a checkpoint inhibitor has revolutionized the treatment of advanced non-small cell lung cancer. Replacing cytotoxic chemotherapy in some settings, immunotherapy with checkpoint inhibitors enables many patients to live longer with much fewer side effects. Nonetheless, immunotherapy alone only works for about one-fifth of unselected patients and despite the durability of response, treatment will eventually fail.

Systemic therapy for advanced hepatocellular carcinoma: targeted therapies.

Therapeutic options for advanced, unresectable hepatocellular carcinoma (HCC) have changed dramatically over the last 3 years. While surgical resection, orthotropic liver transplantation, and localized therapeutic options such as ablation, radiation therapy, and embolization remain therapeutics of choice in localized disease, systemic therapy is the only option in advanced, metastatic HCC. Since the United States Food and Drug Administration (US FDA) approval of sorafenib in 2008, targeted therapies such as sunitinib, tivantinib, brivanib, erlotinib, and linifanib; monoclonal antibody- bevacizumab showed no meaningful improvement in treatment of HCC.

Survival and prognostic factors in patients with rectal squamous cell carcinoma.

Background: Squamous cell carcinoma (SCC) of the rectum is a rare form of gastrointestinal malignancy. The current knowledge on the natural history is primarily derived from case series.

Methods: Using the National Cancer Data Base (NCDB), we determined the prognostic factors and overall survival (OS) outcomes of rectal SCC reported to NCDB between 2004 and 2015.

A Novel Clinically Based Staging System for Gallbladder Cancer.

Background: Current staging systems for gallbladder cancer (GBC) are primarily based on surgical pathology and therefore are not relevant for unresectable patients and those undergoing neoadjuvant chemotherapy.

Methods: Patients with a confirmed diagnosis of GBC managed at a tertiary referral center (2000-2016) were included. Independent predictors of overall survival (OS) were identified using multivariable analysis (MVA).

The Impact of Ramucirumab Treatment on Survival and Quality of Life in Patients with Gastric Cancer.

Gastric cancer is the sixth most common cancer and is known to be the fifth-leading cause of cancer-related deaths globally in 2018. Systemic therapy remains the only curative option in advanced gastric carcinoma with the primary goal of improving the Health-related Quality of Life (HRQoL) (including palliation of symptoms such as dysphagia) and prolonging overall survival. Recently, ramucirumab is approved by the United States Food and Drug Administration (US-FDA) as a second-line agent either as monotherapy or in combination with paclitaxel in advanced or metastatic gastric and gastro-esophageal junction adenocarcinoma patients who have progressed on prior treatment with fluoropyrimidine or platinum containing chemotherapy.

Novel staging system using carbohydrate antigen (CA) 19-9 in extra-hepatic cholangiocarcinoma and its implications on overall survival.

Background: CA19-9 elevation has shown to be associated with poor prognosis in extrahepatic cholangiocarcinoma (ECCA). However, the role of CA19-9 in staging of ECCA has not been evaluated. We hypothesized that CA19-9 elevation is a marker of aggressive biology in ECCA and that inclusion of CA19-9 in the staging system may improve overall survival (OS) discrimination.

Second-line therapies in advanced biliary tract cancers.

Biliary tract cancers constitute approximately 3% of gastrointestinal malignancies with poor prognosis. Surgical therapy is the main form of treatment in localised disease; however, for patients with advanced stage or unresectable disease, locoregional and systemic chemotherapeutics are primary treatment options. Although the combination of gemcitabine and cisplatin is a standard regimen of choice, there are no consensus guidelines that help in choosing an appropriate second-line therapy.

Evaluating the Safety and Efficacy of Nivolumab in Patients with Advanced Hepatocellular Carcinoma: Evidence to Date.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a dismal prognosis, especially when diagnosed at advanced stages. Surgical resection of the primary lesion, liver-directed therapies, and orthotropic liver transplantation are employed in localized disease depending upon the clinical status, underlying liver function, the size, and location of the liver lesions. Systemic therapy plays a critical role in the management of advanced HCC.