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Background: Despite the effectiveness of the various targeted therapies currently approved for solid tumors, acquired resistance remains a persistent problem that limits the ultimate effectiveness of these treatments. Polyclonal resistance to targeted therapy has been described in multiple solid tumors through high-throughput analysis of multiple tumor tissue samples from a single patient. However, biopsies at the time of acquired resistance to targeted agents may not always be feasible and may not capture the genetic heterogeneity that could exist within a patient. Methods: We analyzed circulating tumor DNA (ctDNA) with a large next-generation sequencing panel to characterize the landscape of secondary resistance mechanisms in two independent prospective cohorts of patients (STING: n = 626; BIP: n = 437) with solid tumors who were treated with various types of targeted therapies: tyrosine kinase inhibitors, monoclonal antibodies and hormonal therapies. Results: Emerging alterations involved in secondary resistance were observed in the plasma of up 34% of patients regardless of the type of targeted therapy. Alterations were polyclonal in up to 14% of patients. Emerging ctDNA alterations were associated with significantly shorter overall survival for patients with some tumor types. Conclusion: This comprehensive landscape of genomic aberrations indicates that genetic alterations involved in secondary resistance to targeted therapy occur frequently and suggests that the detection of such alterations before disease progression may guide personalized treatment and improve patient outcome. [ABSTRACT FROM AUTHOR]

Background: Anti-PD1/PDL1 immune checkpoint inhibitors (ICI) transformed the prognosis of patients with advanced non-small cell lung cancer (NSCLC). However, the response rate remains disappointing and toxicity may be life-threatening, making urgent identification of biomarkers predictive for efficacy. Immunologic Constant of Rejection signature (ICR) is a 20-gene expression signature of cytotoxic immune response with prognostic value in some solid cancers. Our objective was to assess its predictive value for benefit from anti-PD1/PDL1 in patients with advanced NSCLC. Methods: We retrospectively profiled 44 primary tumors derived from NSCLC patients treated with ICI as single-agent in at least the second-line metastatic setting. Transcriptomic analysis was performed using the nCounter® analysis system and the PanCancer Immune Profiling Panel. We then pooled our data with clinico-biological data from four public gene expression data sets, leading to a total of 162 NSCLC patients treated with single-agent anti-PD1/PDL1. ICR was applied to all samples and correlation was searched between ICR classes and the Durable Clinical Benefit (DCB), defined as stable disease or objective response according to RECIST 1.1 for a minimum of 6 months after the start of ICI. Results: The DCB rate was 29%; 22% of samples were classified as ICR1, 30% ICR2, 22% ICR3, and 26% ICR4. These classes were not associated with the clinico-pathological variables, but showed enrichment from ICR1 to ICR4 in quantitative/qualitative markers of immune response. ICR2-4 class was associated with a 5.65-fold DCB rate when compared with ICR1 class. In multivariate analysis, ICR classification remained associated with DCB, independently from PDL1 expression and other predictive immune signatures. By contrast, it was not associated with disease-free survival in 556 NSCLC TCGA patients untreated with ICI. Conclusion: The 20-gene ICR signature was independently associated with benefit from anti-PD1/PDL1 ICI in patients with advanced NSCLC. Validation in larger retrospective and prospective series is warranted. [ABSTRACT FROM AUTHOR]

Background Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor beta receptor II (a TGF-β "trap") fused to a human immunoglobulin G1 monoclonal antibody blocking programmed cell death 1 ligand 1 (PD-L1). We report the efficacy and safety in patients with non-small cell lung cancer (NSCLC) that progressed following anti-PD-(L)1 therapy. Materials and Methods In this expansion cohort of NCT02517398—a global, open-label, phase I trial—adults with advanced NSCLC that progressed following chemotherapy and was primary refractory or had acquired resistance to anti-PD-(L)1 treatment received intravenous bintrafusp alfa 1200 mg every 2 weeks until confirmed progression, unacceptable toxicity, or trial withdrawal. The primary endpoint was best overall response (by Response Evaluation Criteria in Solid Tumors version 1.1 adjudicated by independent review committee); secondary endpoints included safety. Results Eighty-three eligible patients (62 [74.7%] treated with ≥3 prior therapies) received bintrafusp alfa. Four patients (3 primary refractory, 1 acquired resistant) had confirmed partial responses (objective response rate, 4.8%; 95% CI, 1.3%-11.9%), and 9 had stable disease. Tumor cell PD-L1 expression was not associated with response. Nineteen patients (22.9%) experienced grade ≥3 treatment-related adverse events, most commonly asthenia (3 [3.6%]) and fatigue, eczema, and pruritus (2 each [2.4%]). One patient had grade 4 amylase increased. One patient died during treatment for pneumonia before initiation of bintrafusp alfa. Conclusion Although the primary endpoint was not met, bintrafusp alfa showed some clinical activity and a manageable safety profile in patients with heavily pretreated NSCLC, including prior anti-PD-(L)1 therapy. Tumor responses occurred irrespective of whether disease was primary refractory or had acquired resistance to prior anti-PD-(L)1 therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: There have been huge improvements in both vaccination and the management of COVID-19 in patients with cancer. In addition, different variants may be associated with different presentations. Therefore, we examined whether indicators of the severity of COVID-19 in patients with cancer who present to hospital varied during different waves of the pandemic and we showed that these indicators remained predictive. We validated that the COVID-19 Risk in Oncology Evaluation Tool (CORONET), which predicts the severity of COVID-19 in cancer patients presenting to hospital, performed well in all waves. In addition, we examined patient outcomes and the factors that influence them and found that there was increased vaccination uptake and steroid use for patients requiring oxygen in later waves, which may be associated with improvements in outcome. Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Background: A phase Ia/Ib trial of metronomic oral vinorelbine (MOV) driven by a mathematical model was performed in heavily pretreated metastatic Non-Small Cell Lung Cancer or Pleural Mesothelioma patients. Disease Control Rate, progression free survival, toxicity and PK/PD were the main endpoints.Methods: Best MOV scheduling was selected using a simplified phenomenological, semi-mechanistic model with a total weekly dose of 150-mg vinorelbine. Computation of individual PK parameters was performed using population approach.Results: The mathematical model proposed the following metronomic schedule for a 150-mg weekly dose of vinorelbine: 60 mg D1, 30 mg D2, 60 mg D4. A total of 37 heavily pre-treated patients (30 evaluable) were enrolled. Grade III/IV neutropenia was observed in 30% patients. Median PFS was 11 weeks. Disease Control Rate was 73% (i.e.; 13% partial response and 60% stable disease). A large variability in drug exposure (AUC0-24 h: 53%) and PK parameters (Cl: 83%) were observed among patients. Simulated trough levels after D2 and D4 showed similarly 56-73% variability among patients. Drug exposure was not associated with efficacy, but neutropenia was more frequent in patients with AUC > 250 ng/ml.h. Tumor burden, performance status and neutrophils-to-lymphocyte ratio (NLR) were associated with PFS, suggesting that MOV would be indicated in selected patients. We built a composite score to predict efficacy, mixing baseline tumor size and NLR showing 84% selectivity and 75% specificity.Conclusions: MOV was characterized by important variability in drug exposure among patients. However, and despite being all heavily pre-treated, 73% of disease control rate and 11 weeks PFS were achieved with manageable toxicities. PK/PD relationships yielded conflicting results depending on the initial tumor burden and BSA, suggesting that patients should be carefully selected prior to be scheduled for metronomic regimen. Possible role NLR could play as a predictive marker suggests immunomodulating features with MOV. [ABSTRACT FROM AUTHOR]

PURPOSE: Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET). METHODS: Patients with active cancer (stage I-IV) and laboratory-confirmed COVID-19 disease presenting to hospitals worldwide were included. Discharge (within 24 hours), admission (≥ 24 hours inpatient), oxygen (O2) requirement, and death were combined in a 0-3 point severity scale. Association of features with outcomes were investigated using Lasso regression and Random Forest combined with Shapley Additive Explanations. The CORONET model was then examined in the entire cohort to build an online CORONET decision support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Finally, the CORONET model was validated on an external cohort. RESULTS: The model development data set comprised 920 patients, with median age 70 (range 5-99) years, 56% males, 44% females, and 81% solid versus 19% hematologic cancers. In derivation, Random Forest demonstrated superior performance over Lasso with lower mean squared error (0.801 v 0.807) and was selected for development. During validation (n = 282 patients), the performance of CORONET varied depending on the country cohort. CORONET cutoffs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died (94% and 98% in validation, respectively). The specificity for mortality prediction was 92% and 83% in derivation and validation, respectively. Shapley Additive Explanations revealed that National Early Warning Score 2, C-reactive protein, and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation. CONCLUSION: CORONET, a decision support tool validated in health care systems worldwide, can aid admission decisions and predict COVID-19 severity in patients with cancer. CORONET, a tool to aid admission decisions for patients with cancer + COVID-19 disease and predict its severity. [ABSTRACT FROM AUTHOR]

Purpose: An assessment of the impact of functional status (FS) evaluated using a combination of Activities of Daily Living (ADL) and the short version of the Instrumental Activities of Daily Living (IADL), on 3- and 6- month mortality and on 3-month unplanned hospitalizations in older patients treated for lung cancers.Method and Objectives: This observational retrospective study was conducted between September 2015 and January 2019 at Marseille University Hospital (AP-HM). During this period, all consecutive outpatients aged 70 years or older referred for a comprehensive geriatric assessment (CGA) before the initiation of lung cancer treatment were enrolled.Results: Two hundred twenty-seven patients were analyzed: the median age was 78.7 years and 74.0% were male. Almost half of the patients were metastatic (45.4%). Concerning FS, 41.9% of patients had no ADL-IADL impairment, 30.0% had either IADL or ADL impairment, and both ADL-IADL were impaired for 28.1%. Impaired ADL-IADL was associated with poor nutritional status, depression, mobility, and cognitive disorders. In a logistic regression model, ADL or IADL impairment (aOR = 2.1; 95% CI [1.0-4.2]; p = 0.037) and impaired ADL-IADL (aOR = 2.6; 95% CI [1.2-5.3]; p = 0.012) were independently associated with a higher risk of unplanned hospitalizations within 3 months. In the multivariate Cox model, 6-month mortality risk was independently associated with impaired ADL-IADL (aHR = 2.3; 95% CI [1.3-4.4]; p = 0.008).Conclusion: The combination of ADL and IADL scales to assess FS is a prognostic marker of the mortality risk at 6 months in older patients with lung cancer and should be more largely used by oncologists in treatment decision making. [ABSTRACT FROM AUTHOR]

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved outcomes in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC). However, almost all patients eventually develop progressive disease on first-line ALK TKIs (e.g., crizotinib, alectinib and ceritinib). Brigatinib, a second-generation ALK TKI, may show efficacy in alectinib- and ceritinib-refractory ALK+ NSCLC. We describe the rationale and design of ALTA-2, a Phase II study of brigatinib in patients with locally advanced/metastatic ALK+ NSCLC and documented progressive disease on alectinib or ceritinib. The primary end point is confirmed objective response rate per independent review committee using response evaluation criteria in solid tumors version 1.1. Secondary end points include duration of response, progression-free survival, overall survival, safety and health-related quality of life. [ABSTRACT FROM AUTHOR]

Background: A Comprehensive Geriatric Assessment (CGA) has been proposed to assess prognosis and to adapt oncological care in older patients with cancer. However, few biological markers are incorporated in the CGA. Methods: This comparative study on older patients with cancer was realized before final therapeutic decision and during a CGA that included biological markers. Our objective study was to know if the serum vitamin B12–C‐reactive protein index (BCI) can help to estimate early death and unplanned hospitalization. Associations between BCI and unplanned hospitalization or mortality were analyzed using ordered multivariate logistic regression. Findings: We included 621 older cancer adults in outpatient care with a median age of 81 years (range, 70–98 years) from September 2015 to May 2018. In this study, 5.6% of patients died within 3 months, 8.8% had unplanned hospitalization within 1 month, and 11.4% had unplanned hospitalization within 3 months. Hypercobalaminemia was present in 83 patients (13.4%), and 34 patients (5.5%) had BCI >40,000. According to the multivariate analysis, BCI was a prognostic factor of mortality within 3 months and unplanned hospitalizations at 1 and 3 months. Impaired activities of daily living (ADL) and palliative care were also risk factors for mortality within 3 months. Impaired instrumental ADL, low albumin level, and palliative care were risk factors for unplanned hospitalization at 1 month. Interpretation: BCI could be routinely added to the CGA process, as part of a pretreatment workup, in order to assess more precisely the frailties and to adapt oncological care in older patients treated for cancer. Implications for Practice: Aging comes with an increase of frailties and comorbidities. To identify frailties in older patients with cancer, this study used a Comprehensive Geriatric Assessment, which allowed for the adaptation of each treatment plan in accordance with the individual needs of the patients. However, biological characteristics were not included in this assessment. This study showed that hypercobalaminemia and vitamin B12 ‐C‐reactive protein index may be potential markers for cancer with poor prognosis, particularly in the older population. These biological markers can be used in geriatric oncology and general medicine. The development of the Comprehensive Geriatric Assessment has improved the management of older patients with cancer. This article suggests the need to include biological markers, focusing on high serum vitamin B12 levels and the vitamin B12/C‐reactive protein index a possible prognostic indicators in older patients treated for cancer. [ABSTRACT FROM AUTHOR]

Introduction: JUNIPER compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, with erlotinib in patients with non-small cell lung cancer (NSCLC) harboring a Kirsten rat sarcoma (KRAS) mutation. Methods: JUNIPER was a Phase III, multicenter, randomized, open-label trial of abemaciclib versus erlotinib in patients with stage IV NSCLC and a detectable mutation in codons 12 or 13 of the KRAS oncogene, who progressed after platinum-based chemotherapy and 1 additional therapy (could include immune checkpoint inhibitor therapy). Randomized patients (3:2) received either 200 mg abemaciclib twice daily or 150 mg erlotinib once daily with best supportive care until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS); secondary endpoints included overall response rate (ORR), progression-free survival (PFS), and safety. Results: Between December 2014 and April 2017, 453 patients were randomly assigned to receive abemaciclib (N = 270) or erlotinib (N = 183). Median OS was 7.4 months (95% confidence interval [CI]: 6.5, 8.8) with abemaciclib and 7.8 months (95% CI: 6.4, 9.5) with erlotinib (hazard ratio [HR] = 0.968 [95% CI: 0.768, 1.219]; p =.77). Median PFS was 3.6 months (95% CI: 2.8, 3.8) with abemaciclib and 1.9 months (95% CI: 1.9, 2.0) with erlotinib (HR = 0.583 [95% CI: 0.470, 0.723]; p <.000001). ORR was 8.9% and 2.7% (p =.010), and the disease control rate was 54.4% and 31.7% (p <.001) with abemaciclib and erlotinib, respectively. Safety results reflected the known safety profiles of abemaciclib and erlotinib. Conclusions: In this study, the primary endpoint of OS was not met; PFS and ORR were improved with manageable toxicity in the abemaciclib arm. The increases in response rates and PFS support further investigation of abemaciclib in other NSCLC subpopulations or in combination with other agents. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02152631 [ABSTRACT FROM AUTHOR]

A novel coronavirus, SARS-CoV-2, was first reported as a respiratory illness in December 2019 in Wuhan, China. Since then, the World Health Organization (WHO) Emergency Committee declared a global health. COVID-19 has now spread worldwide and is responsible of more than 472,216 persons, out of 9,100,090 officially diagnosed worldwide since 23 of June. In the context of cancer patients, COVID-19 has a severe impact, regarding pulmonary infection but also cancer treatments in this fragile and immunocompromised population, and ICU admission for cancer patients in the context of COVID-19 requires ethical and clinical consideration. In our cancer center, intensivists, oncologists, pharmacists, and hospital administrators had to prepare for a substantial increase in critical care bed capacity (from 10 ICU beds, 6 medical intensive care beds, and 12 surgical intensive care beds, bed capacity was increased to 28 medical intensive care beds with ventilating capacity) and to adapt infrastructure (i.e., ICU beds), supplies (i.e., drugs, ventilators, protective materials), and staff (i.e., nurses and medical staff). Overall, thirty-three COVID-19 patients were admitted in our ICU, 17 cancer-free and 16 with cancer, and 23 required mechanical ventilation, resulting in 4 deaths (of them two patients with cancer). We report here management of a dedicated intensive care unit of a cancer center during the COVID-19 infection pandemic, considering resource allocation and redistribution of healthcare workers. [ABSTRACT FROM AUTHOR]

Numerous studies have shown the impact of lung cancer disease on patient quality of life (QoL), but no research has yet examined the impact of illness representations (IR) in the assessment of QoL in lung cancer. Our goal is to explore the role of IR as adeterminant of QoL for lung cancer patients. Data were collected from 162 French patients who completed aself-administered questionnaire including ageneric measure of QoL. It also contains aspecific measure of psychological distress, mental adjustment to cancer, and socio-demographic and medical data. Regression analysis revealed that consequences, treatment control, identity and understanding predicted QoL and the activity dimension of QoL. Perceived consequences and identity seemed to have adeleterious impact on QoL, while treatment control predicted abetter QoL, related to the level of psychological distress and education level. The results suggest the importance of considering IR as adeterminant of QoL. They corroborate earlier findings on the relationship between IR and QoL associated with other pathologies. Psychosocial variables appeared to have more impact on QoL than socio-demographic and clinical variables, which shows the importance of considering IR in order to improve the QoL of patients. [ABSTRACT FROM AUTHOR]

Background: Polymorbidity induces polypharmacy in older patients may lead to potential drug–drug interactions (DDI) which can modify the tolerance and safety of oncological treatments and alter the intended therapeutic effect. The objective of our study was to describe the decision-making process for oncological treatment and related outcomes, in a population of older adults undergoing a comprehensive geriatric assessment (CGA) associated to a comprehensive medication reconciliation (CMR) prior to initiating oncological treatment. Methods: ChimioAge is a prospective observational study conducted between 01/2017 and 07/2018 at Marseille University Hospital and approved by the French National Ethics Committee. It comprised all consecutive patients aged 70 years and over who were referred for a CGA as part of CMR, before initiating systemic treatment. Results: One hundred and seventy-one cancer patients were included. Mean age was 79.2 years, over half had metastatic cancers, 75% had an ECOG performance status zero or one, and two-thirds were independent in daily activities. Two-thirds of the patients had polypharmacy and the CMR identified potential DDI with systemic treatment in 43.3% of patients. Following the CGA, the CMR and the hospital oncologists decision, 30% of the patients received adapted systemic treatment with reduced doses at initiation. They presented fewer toxicities – irrespective of grade and type – than patients who received standard treatment (p< 0.001) and had comparable overall survival (Log rank p=0.21). Conclusion: This is one of the first studies to highlight the value in conducting CMR and a CGA simultaneously before initiating systemic treatment in older patients with cancer. These two evaluations could give oncologists decisive information to personalize cancer treatment of older patients and optimize treatment dose to offer the best efficacy and minimize toxicity. [ABSTRACT FROM AUTHOR]

The advent of molecular targets for novel therapeutics in oncology, notably for non–small cell lung carcinoma (NSCLC), led the French National Cancer Institute (INCa) to establish a national network of 28 hospital Molecular Genetics Centers for Cancer (MGCC) in 2007. In each University in France, laboratories were established to develop molecular biology testing to evaluate a few genomic alterations, initially a selection of genes, by using specific targeted polymerase chain reaction (PCR) assays. In a second phase, the number of studied genes was increased. In 2015, the MGCC benefited from an additional dedicated budget from the INCa to develop next‐generation sequencing (NGS) technology. In the meantime, a new financial regulation for innovative testing has been established for the acts out of nomenclature. Consequently, all private and public laboratories in France have access to funding for molecular biology testing in oncology. The gene‐based PCR assays or NGS tests have benefitted from reimbursement of cost testing by the INCa. Today, the laboratories consider this reimbursement to be only partial, and its use to be complex. In 2018, a strategic plan for medical genomic analyses (France Médecine Génomique 2025) was implemented to introduce more systematic sequencing into the health care pathway and oncology practice. The large panel of molecular tests should be centralized to a limited number of molecular genetic centers. This review describes the evolution of the different stages of implementation of molecular pathology testing for NSCLC patients over the last few years in France. This review describes the evolution of the different stages of implementation of molecular pathology testing for lung cancer patients in France since 2007. The increasing number of genomic alterations in these patients should be assessed to propose the best therapeutic strategy. [ABSTRACT FROM AUTHOR]

In this article, we studied geographic variation in the use of personalized genetic testing for advanced non-small cell lung cancer (NSCLC) and we evaluated the relationship between genetic testing rates and local socioeconomic and ecological variables. We used data on all advanced NSCLC patients who had a genetic test between April 2012 and April 2013 in France in the frame of the IFCT Biomarqueurs-France study (n = 15814). We computed four established measures of geographic variation of the sex-adjusted rates of genetic testing utilization at the "départment" (the French territory is divided into 94 administrative units called 'départements') level. We also performed a spatial regression model to determine the relationship between département-level sex-adjusted rates of genetic testing utilization and economic and ecological variables. Our results are the following: (i) Overall, 46.87% lung cancer admission patients obtained genetic testing for NSCLC; département-level utilization rates varied over 3.2-fold. Measures of geographic variation indicated a relatively high degree of geographic variation. (ii) there was a statistically significant relationship between genetic testing rates and per capita supply of general practitioners, radiotherapists and surgeons (negative correlation for the latter); lower genetic testing rates were also associated with higher local poverty rates. French policymakers should pursue effort toward deprived areas to obtain equal access to personalized medicine for advanced NSCLC patients. [ABSTRACT FROM AUTHOR]

The past couple of years have seen an unprecedented number of failures of clinical trials investigating combinatorial strategies with immuno-oncology drugs (IODs). Importantly, the pharmacokinetics of most therapeutic monoclonal antibodies is characterized by large interindividual variability and reduced ability to diffuse out of the vascular space and reach solid tumors.[24] Therefore, to what extent differences in nivolumab dosing could affect or not target engagement at the tumor levels, and not only in circulating T cells, remains to be fully investigated. Nat Rev Clin Oncol; 13: 242-254, 2016 31 Meille C, Barbolosi D, Ciccolini J, et al: Revisiting dosing regimen using pharmacokinetic/pharmacodynamic mathematical modeling: Densification and intensification of combination cancer therapy. [Extracted from the article]

EVIDENS is an ongoing, prospective, non-interventional study evaluating the effectiveness and safety of nivolumab in lung cancer patients in France (ClinicalTrials.gov NCT03382496). Adults with a pathologically confirmed diagnosis of lung cancer and initiating treatment with nivolumab were recruited from 146 sites in France. This analysis included only patients with non-small cell lung cancer (NSCLC) who received ≥1 nivolumab infusion, and evaluated patient characteristics at the time of nivolumab initiation and its effectiveness and safety after a median follow-up of 18 months. A total of 1,420 patients with NSCLC were included, most of whom had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1 (82.9%), non-squamous histology (69.2%) and stage IV disease (91.4%). Brain metastases were present in 19.9% of patients. Nivolumab was a second-line or ≥third-line regimen in 73.6% and 26.1% of patients, respectively. Almost all patients had prior chemotherapy (99.7%). Median overall survival was 11.2 months (95% confidence interval [CI]: 10.0–12.4). ECOG PS, smoking status, corticosteroids at baseline, epidermal growth factor receptor mutation status, presence of symptomatic brain metastases and treatment-related adverse events (TRAEs) were independent predictors of survival. Grade 3 and 4 TRAEs were reported in 105 (7.4%) and 12 (0.8%) patients, respectively; no treatment-related deaths were reported. Preliminary results of the EVIDENS study confirm the effectiveness and safety of nivolumab, mostly in pre-treated advanced NSCLC patients, with similar benefits to those observed in the phase III randomized clinical trials, despite a broader study population. [ABSTRACT FROM AUTHOR]

Introduction: Several non-comparative phase II studies have evaluated metronomic oral vinorelbine (MOV) in metastatic non-small cell lung cancer (NSCLC) but the small size of each study limits their conclusions. Purpose: To perform an individual patient-data metaanalysis of studies evaluating MOV in metastatic NSCLC in order to measure survival and safety of treatment with this regimen. Methods: Studies were selected if (1) administration of oral vinorelbine thrice a week; (2) fixed daily dose comprised between 30 and 50 mg, and; (3) being published before October 4th 2018. Database encompassed 8 variables characterizing disease and demography, 3 informing therapy, and 12 describing survival and toxicity. Results: Nine studies encompassing 418 patients fulfilled the selection criteria, 80% of them having frailty characteristics. Median overall survival (OS) was 8.7 months (95%CI: 7.6–9.5). OSrates at 6 months, one year and at two years after starting vinorelbine were 64%, 30.3% and 8.9%, respectively. In the Cox model, Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2, and anemia of any grade were significant determinants of shorter OS. Median progression-free survival(PFS) was 4.2 months (95%CI: 3.9–5). At 6 months and at one-year, PFS rates were 35% and 11.9% respectively. In the Cox model stratified for the variable "study", PS = 2and stage IV were significant determinants of shorter PFS. No toxicity was reported for 40% of patients, and 66 (15.8%) patients experienced a grade 3–4 toxicity. The most frequent toxicity was anemia of any grade (35.8%) that was higher with the 50 mg dosage. Conclusion: MOV is an active and well-tolerated chemotherapy in metastatic NSCLC and is a manageable therapy in frail patients. [ABSTRACT FROM AUTHOR]

Bevacizumab‐pemetrexed/cisplatin (BEV‐PEM/CIS) is a first‐line therapeutic for advanced nonsquamous non‐small cell lung cancer. Bevacizumab potentiates PEM/CIS cytotoxicity by inducing transient tumor vasculature normalization. BEV‐PEM/CIS has a narrow therapeutic window. Therefore, it is an attractive target for administration schedule optimization. The present study leverages our previous work on BEV‐PEM/CIS pharmacodynamic modeling in non‐small cell lung cancer–bearing mice to estimate the optimal gap in the scheduling of sequential BEV‐PEM/CIS. We predicted the optimal gap in BEV‐PEM/CIS dosing to be 2.0 days in mice and 1.2 days in humans. Our simulations suggest that the efficacy loss in scheduling BEV‐PEM/CIS at too great of a gap is much less than the efficacy loss in scheduling BEV‐PEM/CIS at too short of a gap. [ABSTRACT FROM AUTHOR]

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Introduction: Companion diagnostic tests (CDXs) are considered mandatory for decision-making for treatment with targeted therapies in thoracic oncology. The emergence of immunotherapy has also given rise to the development of CDXs. Some CDXs, in particular PD-L1 immunohistochemistry tests, have been questioned and re-examined for use with new combination therapies that are being evaluated in clinical trials. Current questions include: Can we establish therapeutic indications in thoracis oncology without CDXs? Would the addition of new tests benefit patient outcome? Areas covered: This review covers the use of CDXs for decision-making in the treatment of lung cancer but also covers the limits of certain tests. It discusses the major challenges for present and future development of CDXs in daily practice. Expert opinion: CDXs can predict the efficacy of drugs if crucial steps in development and validation are fully controlled. Future development of CDXs must consider the detection of biomarkers of resistance and toxicity that are complementary to CDXs predicting therapeutic drug efficacy. Certain CDXs that have already been developed may be of interest for new indications in the field of thoracic oncology. [ABSTRACT FROM AUTHOR]