Clinical and economic impact of pharmacist interventions to identify drug-related problems in multidisciplinary cancer care: a prospective trial.

Background: The prescription of antitumor drugs has often been associated with drug-related problems. Pretherapeutic multidisciplinary risk assessment programs including pharmaceutical care have been established to secure the initiation of injectable and oral antitumor therapies. This prospective cross-sectional double-center study evaluated the clinical and economic impact of the pharmacist in detecting drug-related problems in patients initiating antitumor therapies.

Relationship between energetic gap and sensitivity to anti-programmed cell death 1 immune checkpoint inhibitors in non-small cell lung cancer patients: The ELY-2 study.

Background & Aims: We previously reported in the ELY prospective study that increased resting energy expenditure (REE) - so-called hypermetabolism - worsened tumor response, 6-month progression-free (PFS) and overall survival (OS) in metastatic non-small cell lung cancer (mNSCLC) patients treated with immune checkpoint inhibitors (ICI). Here, we investigated the effect of caloric coverage on the sensitivity to ICI.

Methods: We retrospectively analysed a multicentric database of mNSCLC patients treated with ICI.

Extending the dosing intervals of nivolumab: model-based simulations in unselected cancer patients.

Background: Reducing nivolumab dose intensity could increase patients' life quality and decrease the financial burden while maintaining efficacy. The aims of this study were to develop a population PK model of nivolumab based on data from unselected metastatic cancer patients and to simulate extended-interval regimens allowing to maintain minimal effective plasma concentrations (MEPC).

Methods: Concentration-time data (992 plasma nivolumab concentrations, 364 patients) were modeled using a two-compartment model with linear elimination clearance in Monolix software.

A Dysfunctional T-cell Gene Signature for Predicting Nonresponse to PD-1 Blockade in Non-small Cell Lung Cancer That Is Suitable for Routine Clinical Diagnostics.

Purpose: Because PD-1 blockade is only effective in a minority of patients with advanced-stage non-small cell lung cancer (NSCLC), biomarkers are needed to guide treatment decisions. Tumor infiltration by PD-1T tumor-infiltrating lymphocytes (TIL), a dysfunctional TIL pool with tumor-reactive capacity, can be detected by digital quantitative IHC and has been established as a novel predictive biomarker in NSCLC. To facilitate translation of this biomarker to the clinic, we aimed to develop a robust RNA signature reflecting a tumor's PD-1T TIL status.

Effect of Adapted Physical Activity in Patients With Advanced Pancreatic Cancer: The APACaP GERCOR Randomized Trial.

Background: The impact of adapted physical activity (APA) on health-related quality of life (HRQoL) in patients with advanced pancreatic ductal adenocarcinoma (aPDAC) is unknown. This study evaluated whether APA in addition to standard care improved HRQoL in patients who have aPDAC who are receiving first-line chemotherapy.

Patients And Methods: Patients with locally advanced/metastatic PDAC and an ECOG performance status of 0 to 2 were randomized (1:1) to receive standard care (standard arm) or standard care plus a home-based 16-week APA program (APA arm).

Burden of grade 3 or 4 liver injury associated with immune checkpoint inhibitors.

Background & Aims: There is concern about the burden of liver injury in patients with cancer exposed to immune checkpoints inhibitors (ICIs).

Methods: In a retrospective cohort study, we evaluated the likelihood of grade 3/4 liver injury, of grade 3/4 cholestatic liver injury, and of liver failure, as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5, following treatment with ICIs. We compared these occurrences with a group of cancer patients who were propensity-matched and treated with conventional chemotherapy.

Pharmacokinetics/Pharmacodynamics of Dabrafenib and Trametinib for Redifferentiation and Treatment of Radioactive Iodine-Resistant Mutated Advanced Differentiated Thyroid Cancer.

BRAF and MEK inhibitors are cornerstones of the redifferentiation strategy in metastatic radioactive iodine (RAI)-resistant mutant thyroid cancers. We explored the exposure-toxicity relationship for dose-limiting toxicity (DLT) onset in patients treated with dabrafenib and/or trametinib and investigated whether plasma exposure was associated with RAI reuptake. We conducted a retrospective monocentric study in which we reviewed the electronic medical records of patients treated in our institution with a tumor redifferentiation strategy, for whom plasma concentration of dabrafenib, its active metabolite hydroxy-dabrafenib, and trametinib was measured.

Pazopanib pharmacokinetically guided dose optimization in three cancer patients with gastrointestinal resection.

Purpose: Pazopanib is approved in advanced renal cell carcinoma (RCC) and soft-tissue sarcoma at a flat-fixed dose despite a large pharmacokinetics interindividual variability and a narrow therapeutic index. To our knowledge, pazopanib exposure in patients with gastrointestinal resections (GIR) has not been described. This report focuses on feasibility of pharmacokinetics-guided dose escalation in these patients and clinical implications for their management.

Psoas muscle index is not representative of skeletal muscle index for evaluating cancer sarcopenia.

Background: A common method for diagnosing sarcopenia involves estimating the muscle mass by computed tomography (CT) via measurements of the cross-sectional muscle area (CSMA) of all muscles at the third lumbar vertebra (L3) level. Recently, single-muscle measurements of the psoas major muscle at L3 have emerged as a surrogate for sarcopenia detection, but its reliability and accuracy remain to be demonstrated.

Methods: This prospective cross-sectional study involved 29 healthcare establishments and recruited patients with metastatic cancers.

Impact of sarcopenia indexes on survival and severe immune acute toxicity in metastatic non-small cell lung cancer patients treated with PD-1 immune checkpoint inhibitors.

Background & Aims: Sarcopenia has long been associated with higher toxicity induced by anti-cancer treatments and shorter survival in patients with solid tumors. The creatinine-to-cystatin ratio (CC ratio, serum creatinine/cystatin C × 100) and the sarcopenia index (SI, serum creatinine × cystatin C (CysC)-based glomerular filtration rate (eGFR)) are have been reported to be correlated with skeletal muscle mass. The aim of this study is to assess primarily whether the CC ratio and the SI could predict mortality in metastatic non-small cell lung cancer (NSCLC) patients treated with PD-1 inhibitors, and secondarily their impact on severe immune-related adverse effects (irAEs).

Predictive factors associated with pemetrexed acute toxicity.

Purpose: Pemetrexed has shown efficacy as monotherapy or in combination with platinum salts in the treatment of non-small cell lung cancer and mesothelioma. However, severe hematological toxicities induced by pemetrexed-based chemotherapy have been observed. Some studies have suggested that drug interactions may be associated with pemetrexed toxicity.

Cardiac toxicity associated with pharmacokinetic drug-drug interaction between crizotinib and sofosbuvir/velpatasvir: A case report.

This case report describes a pharmacokinetic drug-drug interaction between crizotinib, a tyrosine kinase inhibitor, and sofosbuvir/velpatasvir, a direct-acting antiviral drug, leading to cardiac toxicity. A 75-year-old man, with no cardiovascular history but a diagnosis of metastatic nonsmall cell lung cancer with mesenchymal-epithelial transition exon-14 deletion and hepatitis C virus infection genotype 1A, received both crizotinib and sofosbuvir/velpatasvir. Crizotinib was well tolerated, but 1 week after sofosbuvir/velpatasvir initiation, the patient experienced bilateral lower-limb oedema and class III New York Heart Association dyspnoea.

Biology and Management of High-Grade Chondrosarcoma: An Update on Targets and Treatment Options.

This review provides an overview of histopathology, clinical presentation, molecular pathways, and potential new systemic treatments of high-grade chondrosarcomas (CS), including grade 2−3 conventional, dedifferentiated, and mesenchymal CS. The diagnosis of CS combines radiological and histological data in conjunction with patient clinical presentations. Conventional CS is the most frequent subtype of CS (85%) and represents about 25% of primary bone tumors in adults; they can be categorized according to their bone location into central, peripheral, and periosteal chondrosarcomas.

Primary Cutaneous Mucinous Carcinoma Monitoring: A Role for CA15.3 and CEA?

Primary cutaneous mucinous carcinoma (PCMC) is a rare malignant skin adnexal tumor. Recurrences are most often localized, and long-term follow-up after complete surgery consists essentially of self-examination of skin. We report one case of metastatic PCMC with elevated levels of serum CEA and CA15.

Supplemental parenteral nutrition in cancer care: why, who, when.

Malnutrition is an often-overlooked challenge for patients with cancer. It is associated with muscle mass reduction, poor compliance and response to cancer treatments, decreased quality of life, and reduced survival time. The nutritional assessment and intervention should be a vital part of any comprehensive cancer treatment plan.

Relationship between the creatinine/cystatin C ratio and muscle mass measured by CT-scan in cancer patients.

Background: Sarcopenia is observed in about 50% of cancer patients. Cancer-related sarcopenia negatively affects survival and is a predictive factor of anticancer drug toxicity. Sarcopenia diagnosis is challenging in routine care.

Exposure-Response Analysis of Osimertinib in Patients with Advanced Non-Small-Cell Lung Cancer.

High interindividual variability (IIV) of the clinical response to epidermal growth factor receptor (EGFR) inhibitors such as osimertinib in non-small-cell lung cancer (NSCLC) might be related to the IIV in plasma exposure. The aim of this study was to evaluate the exposure−response relationship for toxicity and efficacy of osimertinib in unselected patients with advanced EGFR-mutant NSCLC. This retrospective analysis included 87 patients treated with osimertinib.

A Profile of Avelumab Plus Axitinib in the Treatment of Renal Cell Carcinoma.

Until recently, the approved first-line treatment for metastatic RCC (mRCC) consisted of tyrosine kinase inhibitors (TKI) targeting the vascular endothelial growth factor receptors (VEGFR) monotherapy. The landscape of first-line treatment has been transformed in the last few years with the advent of immune checkpoint inhibitors (ICI) or VEGFR TKI plus ICI combinations. This article focuses on the profile of one of these ICI plus VEGFR TKI combination, avelumab plus axitinib.