Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies.

Background: CC-90011 is an oral, potent, selective, reversible inhibitor of lysine-specific demethylase 1 (LSD1) that was well tolerated, with encouraging activity in patients who had advanced solid tumors or relapsed/refractory marginal zone lymphoma. The authors present long-term safety and efficacy and novel pharmacodynamic and pharmacokinetic data from the first-in-human study of CC-90011.

Methods: CC-90011-ST-001 (ClincalTrials.

Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma.

Purpose: Lysine-specific demethylase 1 (LSD1) is implicated in multiple tumor types, and its expression in cancer stem cells is associated with chemoresistance. CC-90011 is a potent, selective, and reversible oral LSD1 inhibitor. We examined CC-90011 in advanced solid tumors and relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL).

The Complex Management of Atrial Fibrillation and Cancer in the COVID-19 Era: Drug Interactions, Thromboembolic Risk, and Proarrhythmia.

Purpose Of Review: Cardiotoxicity by anticancer agents has emerged as a multifaceted issue and is expected to affect both mortality and morbidity. This review summarizes clinical challenges in the management of oncological patients requiring anticoagulants for atrial fibrillation (AF) also considering the current outbreak of the COVID-19 (coronavirus disease 2019) pandemic, since this infection can add challenges to the management of both conditions. Specifically, the aims are manyfold: (1) describe the evolving use of direct oral anticoagulants (DOACs) in AF patients with cancer; (2) critically appraise the risk of clinically important drug-drug interactions (DDIs) between DOACs and oral targeted anticancer agents; (3) address expected DDIs between DOACs and candidate anti-COVID drugs, with implications on management of the underlying thrombotic risk; and (4) characterize the proarrhythmic liability in cardio-oncology in the setting of COVID-19, focusing on QT prolongation.

Evolution of cystic airspaces lung lesions on immune checkpoint inhibition in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) can be associated with pulmonary cystic airspaces (pCAs). pCAs are radiologically classified into four types based on whether the nodule or mass extrudes the wall of the pCAs. In most cases, response evaluation of these lesions by Response Evaluation Criteria in Solid Tumors (RECIST) V.

A Phase 1 Study of mTORC1/2 Inhibitor BI 860585 as a Single Agent or with Exemestane or Paclitaxel in Patients with Advanced Solid Tumors.

This phase 1 trial (NCT01938846) determined the maximum tolerated dose (MTD) of the mTOR serine/threonine kinase inhibitor, BI 860585, as monotherapy and with exemestane or paclitaxel in patients with advanced solid tumors. This 3+3 dose-escalation study assessed BI 860585 monotherapy (5-300 mg/day; Arm A), BI 860585 (40-220 mg/day; Arm B) with 25 mg/day exemestane, and BI 860585 (80-220 mg/day; Arm C) with 60-80 mg/m/week paclitaxel, in 28-day cycles. Primary endpoints were the number of patients with dose-limiting toxicities (DLTs) in cycle 1 and the MTD.

Nivolumab Monotherapy and Nivolumab Plus Ipilimumab in Recurrent Small Cell Lung Cancer: Results From the CheckMate 032 Randomized Cohort.

Introduction: Nivolumab monotherapy is approved in the United States for third-line or later metastatic small cell lung cancer based on pooled data from nonrandomized and randomized cohorts of the multicenter, open-label, phase 1/2 trial of nivolumab ± ipilimumab (CheckMate 032; NCT01928394). We report updated results, including long-term overall survival (OS), from the randomized cohort.

Methods: Patients with small cell lung cancer and disease progression after one to two prior chemotherapy regimens were randomized 3:2 to nivolumab 3 mg/kg every 2 weeks or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four cycles followed by nivolumab 3 mg/kg every 2 weeks.

A first-in-human phase I study of SAR125844, a selective MET tyrosine kinase inhibitor, in patients with advanced solid tumours with MET amplification.

Purpose: Dysregulated MET signalling is implicated in oncogenesis. The safety and preliminary efficacy of a highly selective MET kinase inhibitor (SAR125844) was investigated in patients with advanced solid tumours and MET dysregulation.

Methods: This was a phase I dose-escalation (3 + 3 design [50-740 mg/m]) and dose-expansion study.

Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib.

Unlabelled: ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC.Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC.

Tivantinib, a new option for second-line treatment of advanced hepatocellular carcinoma? The experience of Italian centers.

In the last decades the management of hepatocellular carcinoma (HCC) has undergone significant changes following the introduction of novel therapies such as sorafenib, which have improved patient survival. Nevertheless, HCC is still the third most common cause of cancer-related death worldwide. The evidence-based therapy for advanced HCC that is unsuitable for locoregional treatment is limited to sorafenib, with no second-line option available.

Expression of pERK and VEGFR-2 in advanced hepatocellular carcinoma and resistance to sorafenib treatment.

Background & Aims: The study aimed to evaluate the tissue expression of molecules involved in intracellular signalling pathways as predictors of response to sorafenib in advanced hepatocellular carcinoma (HCC).

Methods: We considered 77 patients enrolled into three prospective trials of sorafenib treatment for whom pretreatment tumour tissue was available. The tissue expression of β-catenin, glutamine synthetase (GS), phosphorylated extracellular signal regulated kinase (pERK), phosphorylated v-akt murine thymoma viral oncogene homolog (pAKT) and vascular endothelial growth factor receptor-2 (VEGFR-2) was analysed by immunostaining.

A phase II randomized dose escalation trial of sorafenib in patients with advanced hepatocellular carcinoma.

Background: Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma (HCC). The viability of continuing sorafenib at a higher dosage in patients who experienced radiologic disease progression was investigated.

Methods: Patients who experienced disease progression while on sorafenib 400 mg twice daily were randomized to sorafenib 600 mg twice daily (n = 49) or best supportive care (n = 52).

Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study.

Background: Tivantinib (ARQ 197), a selective oral inhibitor of MET, has shown promising antitumour activity in hepatocellular carcinoma as monotherapy and in combination with sorafenib. We aimed to assess efficacy and safety of tivantinib for second-line treatment of advanced hepatocellular carcinoma.

Methods: In this completed, multicentre, randomised, placebo-controlled, double-blind, phase 2 study, we enrolled patients with advanced hepatocellular carcinoma and Child-Pugh A cirrhosis who had progressed on or were unable to tolerate first-line systemic therapy.

Pain outcomes in patients with advanced breast cancer and bone metastases: results from a randomized, double-blind study of denosumab and zoledronic acid.

Background: In this study, the authors evaluated the effect of denosumab versus zoledronic acid (ZA) on pain in patients with advanced breast cancer and bone metastases.

Methods: The prevention of pain, reduction in pain interference with daily life activities, and the proportion of patients requiring strong opioid analgesics were assessed in a randomized, double-blind, double-dummy phase 3 study comparing denosumab with ZA for preventing skeletal-related events in 2046 patients who had breast cancer and bone metastases. Patients completed the Brief Pain Inventory-Short Form at baseline and monthly thereafter.

Pertuzumab monotherapy after trastuzumab-based treatment and subsequent reintroduction of trastuzumab: activity and tolerability in patients with advanced human epidermal growth factor receptor 2-positive breast cancer.

Purpose: The combination of pertuzumab and trastuzumab resulted in a clinical benefit rate (CBR) of 50% in patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer whose disease progressed during prior trastuzumab-based therapy. To define whether this previously observed encouraging activity was a result of the combination of pertuzumab and trastuzumab or of pertuzumab alone, we recruited a third cohort of patients who received pertuzumab without trastuzumab. We then investigated the impact of reintroducing trastuzumab to patients whose disease progressed on pertuzumab monotherapy.

Activity and safety of dose-adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab in very elderly patients with poor-prognostic untreated diffuse large B-cell non-Hodgkin lymphoma.

Background: This study was designed to assess the activity and safety of dose-adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab (DA-POCH-R) in elderly patients with poor-prognostic untreated diffuse large B-cell non-Hodgkin lymphoma (DLBCL).

Methods: From April 2006 to November 2009, 23 patients, aged ≥70 years, with an age-adjusted International Prognostic Index (IPI) of 2 or 3, were enrolled. Only patients with left ventricular ejection fraction (LVEF) ≥50% were allowed.

Open-label, phase II, multicenter, randomized study of the efficacy and safety of two dose levels of Pertuzumab, a human epidermal growth factor receptor 2 dimerization inhibitor, in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer.

Purpose: Pertuzumab is a humanized monoclonal antibody inhibiting human epidermal growth factor receptor 2 (HER2) dimerization. The aim of this phase II trial was to assess the antitumor activity and safety profile of pertuzumab monotherapy in patients with HER2-negative metastatic breast cancer. The utility of biomarkers detected in paraffin-embedded tissue as predictors of response was also explored.

Phase II multicenter, uncontrolled trial of sorafenib in patients with metastatic breast cancer.

This trial was conducted to assess the efficacy and safety of sorafenib in patients with metastatic breast cancer. In this multinational, open-label phase II study, patients with metastatic breast cancer that had progressed after at least one prior chemotherapy regimen were continuously treated with oral sorafenib, 400 mg twice daily. The primary endpoint was overall best response; a secondary endpoint was percentage of patients with stable disease for greater than or equal to 16 weeks.

Hepatic artery administration of docetaxel in liver metastases from breast carcinoma: a feasibility study.

Aims And Background: Taxanes are largely metabolized and almost exclusively excreted in the feces by the liver through the biliary pathway, thus providing a rationale for investigating the activity of their hepatic artery delivery in case of liver metastases.

Study Design: The aim of this study was to assess the feasibility of administering docetaxel via the hepatic artery in advanced breast cancer patients in whom the liver was the only or the predominant site of metastatic involvement. The dose was increased cycle by cycle in a prospective manner.

Design and development of new combinations of the CMF agents with taxanes (paclitaxel or docetaxel) in advanced breast cancer: a feasibility study.

Aims And Background: We previously designed and tested combinations made up of the CMF agents, two at a time by rotation, and of doxorubicin or epirubicin. The present study was aimed to similarly test new combinations made up of the CMF agents, two at a time by rotation, and paclitaxel or docetaxel.

Methods: The doses of each taxane were escalated with the objective of reaching at least a single dose level of 90 mg/m2 of paclitaxel and 45 mg/m2 of docetaxel on days 1 and 8 of each four-week cycle.

Effects of media information on cancer patients' opinions, feelings, decision-making process and physician-patient communication.

Background: The objective of the current study was to determine the influence of media information on the opinions and feelings of patients with cancer and to measure the factors that affected the decision-making process and physician-patient communication.

Methods: The study consisted of a sequence of 2 nationwide surveys across the same dynamic target population of 2600 unselected patients with cancer who attended 1 of 13 centers throughout Italy. The authors measured the changes in patients' opinions and attitudes at the peak of a media campaign promoting the Di Bella therapy, an unproven cancer treatment method, and after the publicized demonstration of its ineffectiveness.