In the past decade the advent of target therapy has led to a silent revolution in the treatment of lung cancer. Thanks to the specificity of their target, new tailored drugs are able to achieve a larger benefit and lower toxicity and provide better quality of life than cytotoxic drugs in a limited number of patients, selected by molecular profile. Nowadays, the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib, and the anaplastic lymphoma kinase inhibitor crizotinib, are targeted agents approved for treatment of non-small-cell lung cancer. The past decade has witnessed a silent revolution in the war against cancer, thanks to the advent of new therapies, which target specific mutations related to cancer cell proliferation and survival in different types of tumors. Among all cancers, lung cancer remains the leading cause of cancer-related death in most countries, with 159,260 expected deaths in the United States in 2014. Lung cancer occurs predominately in people between 50 and 70 years old, but the risk of developing this cancer reaches a peak in people older than 70 years. Lung cancer incidence decreased in the past two decades in several countries, including the United States, following a decreased rate of smoking. At the same time, the incidence among women, including former or never smokers, is rapidly increasing.1 The discovery of "oncogenic driver mutations" and the subsequent development of tailored agents has radically changed the treatment of lung cancer in ten years, leading to the development of personalized strategies. 2,3 Non-small-cell lung cancer (NSCLC) was traditionally classified, based on histologic features, as adenocarcinoma, squamous cell carcinoma, and other nonspecified subtypes, which represent about 55%, 35%, and 10% of all NSCLC cases, respectively. In the early 1990s treatment approaches available for patients with lung cancer were poor, with a median survival of 2 to 4This article was externally peer reviewed.

Background The strengthening or substitution of intravenous cytotoxic chemotherapy cycles by oral targeted anticancer therapies, such as protein kinase inhibitors (PKIs), has provided impressive clinical benefits and autonomy as well as a better quality of life for patients with cancer. Despite these advances, adverse event management at home and medication adherence remain challenging. In addition, PKI plasma concentrations vary significantly among patients with cancer receiving the same dosage, which could explain part of the observed variability in the therapeutic response. Objective The aim of this optimizing oral targeted anticancer therapies (OpTAT) study is to optimize and individualize targeted anticancer treatments to improve patient care and self-monitoring through an interprofessional medication adherence program (IMAP) combined with measurement PKI plasma concentrations. Methods The OpTAT study has two parts: (1) a 1:1 randomized medication adherence program, in which the intervention consists of regular motivational interviewing sessions between the patient and the pharmacist, along with the delivery of PKIs in electronic monitors, and (2) a systematic collection of blood samples and clinical and biological data for combined pharmacokinetic and pharmacodynamic analysis. On the basis of the electronic monitor data, medication adherence will be compared between groups following the three operational definitions: implementation of treatment during the persistent period, persistence with treatment and longitudinal adherence. The implementation will be described using generalized estimating equation models. The persistence of PKI use will be represented using a Kaplan-Meier survival curve. Longitudinal adherence is defined as the product of persistence and implementation. PKI pharmacokinetics will be studied using a population approach. The relationship between drug exposure and efficacy outcomes will be explored using Cox regression analysis of progression-free survival. The relationship between drug exposure and toxicity will be analyzed using a pharmacokinetic-pharmacodynamic model and by logistic regression analysis. Receiver operating characteristic analyses will be applied to evaluate the best exposure threshold associated with clinical benefits. Results The first patient was included in May 2015. As of June 2021, 262 patients had participated in at least one part of the study: 250 patients gave at least one blood sample, and 130 participated in the adherence study. Data collection is in process, and the final data analysis is planned to be performed in 2022. Conclusions The OpTAT study will inform us about the effectiveness of the IMAP program in patients with solid cancers treated with PKIs. It will also shed light on PKI pharmacokinetic and pharmacodynamic properties, with the aim of learning how to adapt the PKI dosage at the individual patient level to increase PKI clinical suitability. The IMAP program will enable interprofessional teams to learn about patients’ needs and to consider their concerns about their PKI self-management, considering the patient as an active partner. Trial Registration ClinicalTrials.gov NCT04484064; https://clinicaltrials.gov/ct2/show/NCT04484064. International Registered Report Identifier (IRRID) DERR1-10.2196/30090

Ewing sarcoma (ES) is a rare, highly malignant sarcoma. It usually presents in the second decade of life; however, patients can be diagnosed as early as newborns and as late as in their seventies. ES is most frequently found in the long bones of the extremities and the pelvis. In older patients, ES can also arise in the soft tissues. Currently, there is no standard schedule for surveillance of adult patients with ES after their initial treatment for localised disease, not only for the early detection of recurrence but also for long-term side effects. Follow-up is based on group recommendations using extrapolated data obtained primarily from studies with paediatric patients. The main objective of this review is to summarise the data available on treatment-associated complications in long-term survivors. Furthermore, we provide a set of recommendations for optimising the follow-up of adults ES survivors, as well as for managing the sequelae that result from intensive multimodal treatment.

The cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib is administered orally and cyclically, causing medication adherence challenges. We evaluated components of adherence to palbociclib, its relationship with pharmacokinetics (PK), and drug-induced neutropenia. Patients with metastatic breast cancer (MBC) receiving palbociclib, delivered in electronic monitors (EM), were randomized 1:1 to an intervention and a control group. The intervention was a 12-month interprofessional medication adherence program (IMAP) along with monthly motivational interviews by a pharmacist. Implementation adherence was compared between groups using generalized estimating equation models, in which covariates were included. Model-based palbociclib PK and neutrophil profiles were simulated under real-life implementation scenarios: (1) optimal, (2) 2 doses omitted and caught up at cycle end. At 6 months, implementation was slightly higher and more stable in the intervention (n = 19) than in the control (n = 19) group, 99.2% and 97.3% (Δ1.95%, 95% CI 1.1–2.9%), respectively. The impact of the intervention was larger in patients diagnosed with MBC for >2 years (Δ3.6%, 95% CI 2.1–5.4%), patients who received >4 cycles before inclusion (Δ3.1%, 95% CI 1.7–4.8%) and patients >65 (Δ2.3%, 95% CI 0.8–3.6%). Simulations showed that 25% of patients had neutropenia grade ≥3 during the next cycle in scenario 1 versus 30% in scenario 2. Education and monitoring of patient CDK4/6i cycle management and adherence along with therapeutic drug monitoring can help clinicians improve prescription and decrease toxicity.