Publications by authors named "Marie Wislez"

165 Publications

Development and validation of a host-dependent, PDL1-independent, biomarker to predict 6-month progression-free survival in metastatic non-small cell lung cancer (mNSCLC) patients treated with anti-PD1 immune checkpoint inhibitors (ICI) in the CERTIM Cohort: The ELY study.

EBioMedicine 2021 Oct 20;73:103630. Epub 2021 Oct 20.

Medical Oncology Department, Cochin Hospital, AP-HP; Cancer Research for PErsonalized Medicine (CARPEM), Paris, France; Immunomodulatory Therapies Multidisciplinary Study group (CERTIM), Cochin Hospital, AP-HP, 75014 Paris, France; URP 4466 PRETRAM, AP-HP, Paris University, France.

Background: Immune checkpoint inhibitors (ICI) are dramatically active in a minority of non-small cell lung cancer (NSCLC) patients. We studied here the relationship between patients's metabolism and outcome under ICI.

Methods: Metastatic NSCLC patients underwent a nutritional assessment prior to initiating immunotherapy. Resting energy expenditure (REE) was measured (mREE) using ambulatory indirect calorimetry and compared with the theoretical value (tREE) provided by the Harris and Benedict formula. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and disease control rate (DCR) based on investigator review per RECIST v1.1. and overall survival (OS). The association of patient's metabolism with 6-month PFS was first explored in a single-center training cohort to estimate the effect size. The relationship between patient's metabolism and 6-month PFS was then tested in an independent non interventional observational prospective cohort (ELY) of 100 patients recruited in two tertiary university centers.

Findings: In the entire cohort, the ORR was 14% for the hypermetabolic group (n = 10/74) vs 38% for the normometabolic group (n = 26/68), respectively (estimated difference 25%, 95CI 9-40%, p = 0.001). The DCR was 28% for the hypermetabolic group (n = 21/74) vs 53% for the normometabolic group (n = 36/68), respectively (estimated difference 25%, 95CI 7-42%, p = 0.005). In the validation cohort (100 patients, 2 centers), normometabolic patients (defined as mREE/tREE < 110%) had increased 6-month PFS (57% versus 22%; odds ratio: 4.76; IC95 [1.87 - 12.89]; p<0.001) and improved overall survival (HR 2.20; IC95: 1.41-3.44; p<0.001). The positive and negative predictive values of normometabolism to identify non-progressive patients at 6 months, were 57% and 78% respectively, sensitivity was 72% and specificity was 66%. In multivariate analysis including PD-L1 tumor status, basal metabolism was an independent predictive factor for 6-month PFS.

Interpretation: Normometabolism is a new independent parameter to identify mNSCLC patients who will benefit from ICI, with both improved tumor response, 6-month PFS, and survival.

Funding: This work was supported by Baxter (04012016).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2021.103630DOI Listing
October 2021

EGFR Exon 20 Insertion in Metastatic Non-Small-Cell Lung Cancer: Survival and Clinical Efficacy of EGFR Tyrosine-Kinase Inhibitor and Chemotherapy.

Cancers (Basel) 2021 Oct 13;13(20). Epub 2021 Oct 13.

Oncology Thoracic Unit, Pulmonology Department, AP-HP, Hôpital Cochin, F-75014 Paris, France.

EGFR exon 20 insertions are rare genetic alterations in non-small-cell lung cancers (NSCLCs) that are usually unresponsive to approved EGFR tyrosine kinase inhibitors (TKIs). In this paper, we describe the clinical characteristics, efficacy of EFGR TKIs and chemotherapy, and resulting survival in this population. We retrospectively collected patients with EGFR exon 20 insertions (Exon20ins) from 11 French genetic platforms and paired them (1:2 ratio) with classic Exon 19/21 EGFR mutation patients (controls). Between 2012 and 2017, 35 Exon20ins patients were included. These patients were younger at diagnosis than the controls. All Exon20ins patients who were treated with first-line EGFR TKIs ( = 6) showed progressive disease as the best tumor response. There was no significant difference in the tumor response or the disease control rate with first-line platinum-based chemotherapy between the two groups. A trend towards shorter overall survival was observed in Exon20ins vs. controls (17 months (14-not reach(NR) 95% confidence interval(CI) vs. 29 months (17-NR 95%CI), = 0.09), respectively. A significant heterogeneity in amino acid insertion in EGFR exon 20 was observed. EGFR exon 20 insertions are heterogeneous molecular alterations in NSCLC that are resistant to classic EGFR TKIs, which contraindicates their use as a first-line treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13205132DOI Listing
October 2021

Impact of the COVID-19 pandemic on the management of cancer patients: the experience of the cancer outpatients department of a university hospital in Paris.

Clin Med (Lond) 2021 Sep 2;21(5):e552-e555. Epub 2021 Aug 2.

Cochin Hospital, Paris, France.

Cancer patients are a highly vulnerable group in the COVID-19 pandemic and it has been necessary for oncology units to adapt to this unexpected situation. We present our management of outpatients with cancer during the pandemic. We applied two major adaptations: extending the intervals between injections for maintenance therapy and protocol adaptation for patients with comorbidities. Between 17 March and 30 April 2020, 406 patients were treated in our outpatients department. Protocols were adapted for 94 (23.1%) patients. Among them, 49% had an extended interval between treatment administrations, 22.3% had modified protocols to reduce toxicity, 20.2% had therapeutic interruptions and 5.3% did not receive their treatment because of a COVID-19 infection. Overall, protocol adaptations concerned more than 20% of the patients. This pandemic was an opportunity for oncologists to re-examine the risk versus benefit balance of administering immunosuppressive treatment and highlighted that oncology daily routine should not be applied automatically.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7861/clinmed.2020-0666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439500PMC
September 2021

Long-Term Imaging Follow-Up in DIPNECH: Multicenter Experience.

J Clin Med 2021 Jun 30;10(13). Epub 2021 Jun 30.

Department of Radiology, AP-HP. Centre, Hôpital Cochin, 75014 Paris, France.

Diffuse pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pre-invasive disease whose pathophysiology remains unclear. We aimed to assess long-term evolution in imaging of DIPNECH, in order to propose follow-up recommendations. Patients with histologically confirmed DIPNECH from four centers, evaluated between 2001 and 2020, were enrolled if they had at least two available chest computed tomography (CT) exams performed at least 24 months apart. CT exams were analyzed for the presence and the evolution of DIPNECH-related CT findings. Twenty-seven patients, mostly of female gender ( = 25/27; 93%) were included. Longitudinal follow-up over a median 63-month duration (IQR: 31-80 months) demonstrated an increase in the size of lung nodules in 19 patients (19/27, 70%) and the occurrence of metastatic spread in three patients (3/27, 11%). The metastatic spread was limited to mediastinal lymph nodes in one patient, whereas the other two patients had both lymph node and distant metastases. The mean time interval between baseline CT scan and metastatic spread was 70 months (14, 74 and 123 months). Therefore, long-term annual imaging follow-up of DIPNECH might be appropriate to encompass the heterogeneous longitudinal behavior of this disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10132950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268818PMC
June 2021

The rising challenge of oncogene addiction in lung cancer.

Bull Cancer 2021 Jun;108(6):559-561

Hôpital Cochin, Groupe Hospitalier HUPC, Department of Pneumology, Thoracic Oncology Unit, AP-HP, 27, rue du Faubourg Saint-Jacques, Paris, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2021.04.014DOI Listing
June 2021

Risk of lung cancer among women in relation to lifetime history of tobacco smoking: a population-based case-control study in France (the WELCA study).

BMC Cancer 2021 Jun 16;21(1):711. Epub 2021 Jun 16.

Université Paris-Saclay, UVSQ, Inserm U1018, CESP, Team Exposome and Heredity, Villejuif, France.

Background: This study aims to provide new insights on the role of smoking patterns and cigarette dependence in female lung cancer, and to examine differences by histological subtype.

Methods: We conducted a population-based case-control study in the great Paris area among women including 716 incident cases diagnosed between 2014 and 2017 and 757 age-matched controls. Detailed data on smoking history was collected during in-person interviews to assess intensity and duration of tobacco smoking, time since cessation, smoking habits (depth of smoke inhalation, use of filter, type of tobacco, and type of cigarettes) and Fagerström test for cigarette dependence. The comprehensive smoking index (CSI), a score modelling the combined effects of intensity, duration and time since quitting smoking was determined for each subject. Multivariable logistic regression models were fitted to calculate odds ratios (ORs) and their confidence intervals (95%CI) of lung cancer associated with smoking variables.

Results: Lung cancer risk increased linearly with intensity and duration of tobacco smoking while it decreased with time since cessation, to reach the risk in never-smokers after 20 years of abstinence. The combined effect of intensity and duration of tobacco smoking was more than multiplicative (p-interaction 0.012). The OR in the highest vs the lowest quartile of CSI was 12.64 (95%CI 8.50; 18.80) (p-trend < 0.001). The risk of small cell or squamous cell carcinomas increased with the CSI more sharply than the risk of adenocarcinomas. Deep smoke inhalation, dark vs blond tobacco, conventional vs light cigarettes, and unfiltered vs filtered cigarettes, as well as having mixed smoking habits, were found to be independent risk factors. Having high cigarette addiction behaviours also increased the risk after adjusting for CSI.

Conclusion: This study provides additional insights on the effects of tobacco smoking patterns on lung cancer risk among women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-021-08433-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207748PMC
June 2021

Clinicopathologic Features and Response to Therapy of Fusion-Driven Lung Cancers: The eNRGy1 Global Multicenter Registry.

J Clin Oncol 2021 Sep 2;39(25):2791-2802. Epub 2021 Jun 2.

Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.

Purpose: Although fusions are oncogenic drivers across multiple tumor types including lung cancers, these are difficult to study because of their rarity. The global eNRGy1 registry was thus established to characterize fusion-positive lung cancers in the largest and most diverse series to date.

Methods: From June 2018 to February 2020, a consortium of 22 centers from nine countries in Europe, Asia, and the United States contributed data from patients with pathologically confirmed fusion-positive lung cancers. Profiling included DNA-based and/or RNA-based next-generation sequencing and fluorescence in situ hybridization. Anonymized clinical, pathologic, molecular, and response (RECIST v1.1) data were centrally curated and analyzed.

Results: Although the typified never smoking (57%), mucinous adenocarcinoma (57%), and nonmetastatic (71%) phenotype predominated in 110 patients with fusion-positive lung cancer, further diversity, including in smoking history (43%) and histology (43% nonmucinous and 6% nonadenocarcinoma), was elucidated. RNA-based testing identified most fusions (74%). Molecularly, six (of 18) novel 5' partners, 20 unique epidermal growth factor domain-inclusive chimeric events, and heterogeneous 5'/3' breakpoints were found. Platinum-doublet and taxane-based (post-platinum-doublet) chemotherapy achieved low objective response rates (ORRs 13% and 14%, respectively) and modest progression-free survival medians (PFS 5.8 and 4.0 months, respectively). Consistent with a low programmed death ligand-1 expressing (28%) and low tumor mutational burden (median: 0.9 mutations/megabase) immunophenotype, the activity of chemoimmunotherapy and single-agent immunotherapy was poor (ORR 0%/PFS 3.3 months and ORR 20%/PFS 3.6 months, respectively). Afatinib achieved an ORR of 25%, not contingent on fusion type, and a 2.8-month median PFS.

Conclusion: fusion-positive lung cancers were molecularly, pathologically, and clinically more heterogeneous than previously recognized. The activity of cytotoxic, immune, and targeted therapies was disappointing. Further research examining -rearranged tumor biology is needed to develop new therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.03307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407651PMC
September 2021

Circulating tumor DNA in advanced non-small-cell lung cancer patients with HIV is associated with shorter overall survival: Results from a Phase II trial (IFCT-1001 CHIVA).

Lung Cancer 2021 07 13;157:124-130. Epub 2021 May 13.

Université de Paris, Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Team Inflammation, Complement, and Cancer, F-75006 Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Georges Pompidou, Hôpital Cochin, Hôpital Necker, Paris Cancer Institute CARPEM, Paris, France.

Introduction: HIV is an exclusion criterion for most lung cancer (LC) trials, however LC is the most common non-AIDS-defined malignancy in people living with HIV (PLHIV), poorer prognosis than the general population. Circulating tumor DNA (ctDNA) was a prognostic marker in LC patients from the general population. This study assessed ctDNA's prognostic value in PLHIV from a dedicated phase II trial.

Methods: Overall, 61 PLHIV with advanced non-squamous non-small-cell lung cancer (NSCLC) participated in the IFCT Phase II trial evaluating first-line four-cycle carboplatin (Ca) AUC5 pemetrexed (P) 500 mg/m induction therapy every 3 weeks, followed by P maintenance therapy. Blood samples collected before treatment were analyzed to detect ctDNA using ultra-deep targeted next-generation-sequencing (NGS).

Results: Appropriate samples were available from 55 PLVIH and analyzed for ctDNA detection. Including 42 males (76.4 %), 52.9 years median age, 51 smokers (92.7 %), five with non-squamous NSCLC Stage III (9%), 50 Stage IV (91 %), and performance status (PS) 0-2. ctDNA was detected in 35 patients (64 %), 22 with high and 13 with low ctDNA levels. Overall, 77 % were positive for TP53, 29 % for KRAS, and 11 % for STK11 mutations, more than one alteration was detected in 43 % of samples. Multivariate analysis showed that positive ctDNA was significantly associated with shorter PFS (HR, 4.31, 95 %CI: 2.06-8.99, p < 0.0001), and shorter OS (HR, 3.52, 95 %CI: 1.72-7.19, p < 0.001). Moreover, OS was significantly longer for patients with low ctDNA levels at diagnosis as compared to high (p = 0.01).

Conclusion: We show that ctDNA detection using ultra-deep NGS is an independent prognostic factor in PLHIV with advanced NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2021.05.013DOI Listing
July 2021

Short-term and Long-term Outcomes of Patients With Lung Cancer and Life-Threatening Complications.

Chest 2021 Oct 4;160(4):1560-1564. Epub 2021 May 4.

Université de Paris, Paris, France; Institut Cochin, INSERM U1016, Paris, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.04.056DOI Listing
October 2021

Lung carcinoid tumors with Diffuse Idiopathic Pulmonary NeuroEndocrine Cell Hyperplasia (DIPNECH) exhibit pejorative pathological features.

Lung Cancer 2021 06 30;156:117-121. Epub 2021 Apr 30.

Department of Thoracic Surgery, Hôpital Cochin, APHP.CUP, Université de Paris, France. Electronic address:

Introduction: Diffuse Idiopathic Pulmonary NeuroEndocrine Cell Hyperplasia (DIPNECH) is a rare disease often associated with carcinoid tumors. We aimed at evaluating the impact of DIPNECH on characteristics and prognosis of patients who underwent radical treatment of pulmonary carcinoid tumors.

Material And Methods: We reviewed all patients operated on for curative-intent resection of carcinoid tumor in our department from 2001 to 2020. Cases exhibiting both pathological and radiological features of DIPNECH, as assessed by respective thoracic expert physicians, were analyzed separately.

Results: 172 cases of resected carcinoid tumors were identified, including 25 (14.5 %) harboring pathological criteria of DIPNECH and radiologic features like mosaic attenuation (92.0 %), multiple nodules < 5 mm (76.0 %), and mucoid impactions (32 %). In DIPNECH patients, major pulmonary resections were usually performed (92.0 %) and resected tumors were mostly classified as pT1 (92 %). Mean Ki67 staining was 3.7 ± 5.2 %. The early postoperative period was mostly uneventful (96.0 %) and 5-year survival was 92.9 ± 6.9 %. Compared to non-DIPNECH cases, we found that patients were older (mean 65.6 ± 9.3 versus 54.1 ± 17.9, p = 0.002), more frequently female (84.0 % versus 56.5 %, p = 0.009), and exhibiting diabetes mellitus (45.8 % versus 18.5 %, p < 0.001) or hypertension (45.8 % versus 24.1 %, p = 0.039). The rate of atypical carcinoid tumors was significantly higher in DIPNECH patients (40.0 % versus 19.9 %, p = 0.027), as well as rate of mediastinal lymph-nodes involvement (pN2+) (36.0 % versus 4.1 %, p < 0.001). At multivariate analysis, only DIPNECH pattern and atypical histology were independent factors of pN2 invasion which was the only predictor of poorer prognosis on Log-Rank test.

Conclusion: Carcinoid tumors with proven DIPNECH are associated with negative pathological features and may deserve a dedicated perioperative management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2021.04.024DOI Listing
June 2021

Does Very Poor Performance Status Systematically Preclude Single Agent Anti-PD-1 Immunotherapy? A Multicenter Study of 35 Consecutive Patients.

Cancers (Basel) 2021 Mar 2;13(5). Epub 2021 Mar 2.

Department of Thoracic Oncology, Bichat Claude Bernard Hospital, APHP, CIC Inserm 1425, Université de Paris, 75018 Paris, France.

Anti-PD-1 antibodies prolong survival of performance status (PS) 0-1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3-4 patients is unknown. Conse- cutive PS 3-4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3-4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1-7) as first- ( = 6) or second-line ( = 29) therapy. At a median of 52-month follow-up (95%CI, 41-63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1-3.2). Median OS was 4.4 months (95%CI, 0.5-8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9-14.3, = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7-13.8, = 0.003) predicted worse survival. PS improvement from 3-4 to 0-1 ( = 9) led to a median 43-month (95%CI, 0-102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13051040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958129PMC
March 2021

Intergroupe francophone de cancérologie thoracique, Société de pneumologie de langue française, and Société d'imagerie thoracique statement paper on lung cancer screening.

Diagn Interv Imaging 2021 Apr 26;102(4):199-211. Epub 2021 Feb 26.

Université de Paris, F-75006 Paris, France; Department of Radiology, Groupe Hospitalier Bichat-Claude-Bernard, Assistance publique-Hôpitaux de Paris, 75018 Paris, France.

Following the American National Lung Screening Trial results in 2011 a consortium of French experts met to edit a statement. Recent results of other randomized trials gave the opportunity for our group to meet again in order to edit updated guidelines. After literature review, we provide here a new update on lung cancer screening in France. Notably, in accordance with all international guidelines, the experts renew their recommendation in favor of individual screening for lung cancer in France as per the conditions laid out in this document. In addition, the experts recommend the very rapid organization and funding of prospective studies, which, if conclusive, will enable the deployment of lung cancer screening organized at the national level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diii.2021.01.012DOI Listing
April 2021

Immunodynamics of explanted human tumors for immuno-oncology.

EMBO Mol Med 2021 01 29;13(1):e12850. Epub 2020 Dec 29.

Institut Gustave Roussy, Villejuif, France.

Decision making in immuno-oncology is pivotal to adapt therapy to the tumor microenvironment (TME) of the patient among the numerous options of monoclonal antibodies or small molecules. Predicting the best combinatorial regimen remains an unmet medical need. Here, we report a multiplex functional and dynamic immuno-assay based on the capacity of the TME to respond to ex vivo stimulation with twelve immunomodulators including immune checkpoint inhibitors (ICI) in 43 human primary tumors. This "in sitro" (in situ/in vitro) assay has the potential to predict unresponsiveness to anti-PD-1 mAbs, and to detect the most appropriate and personalized combinatorial regimen. Prospective clinical trials are awaited to validate this in sitro assay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/emmm.202012850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799366PMC
January 2021

Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19).

Eur J Cancer 2020 12 8;141:62-81. Epub 2020 Oct 8.

Department of Gastroenterology, Saint Louis Hospital, APHP, Université de Paris, Paris, FFCD, France.

Background: Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated.

Patients And Methods: In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and 11th June 2020. The primary end-point was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary end-points.

Results: From April 4 to 11th June 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), The Eastern Cooperative Oncology Group Performance Scale (ECOG PS) ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except for cytotoxic chemotherapy in the subgroup of patients with detectable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase polymerase chain reaction (RT-PCR), which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment (such as chemotherapy, targeted or immune therapy) interrupted or stopped following diagnosis of COVID-19.

Conclusions: Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2020.09.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543792PMC
December 2020

Nivolumab increases pulmonary artery pressure in patients treated for non-small cell lung cancer.

Cancer Chemother Pharmacol 2020 10 16;86(4):497-505. Epub 2020 Sep 16.

Thoracic Surgery Department, Cochin Hospital, AP-HP.Center-University of Paris, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.

Purpose: The widespread use of Nivolumab results in an increasing number of side effects and adverse events. Herein, we evaluated the impact of Nivolumab on crude and normalized pulmonary artery diameter (PAD).

Methods: We analyzed clinical, morphometric, pathological and radiological data of lung cancer patients treated by Nivolumab in an 18-month period. Blinded radiological evaluation was performed, by three observers measuring axial PAD and Aorta diameter (AoD) in secondarily matched pre- and post-Nivolumab CT-scans. Correlation between ΔPAD and clinicopathological data was investigated.

Results: 59 patients receiving Nivolumab for treatment of advanced lung carcinoma were identified. Pre-and post-Nivolumab comparison of CT-scan measures revealed that mean PAD was 26.3 ± 2.8 mm versus 28.0 ± 3.0 mm (p < 0.001), and mean PAD/AoD ratio was 0.82 ± 0.09 versus 0.87 ± 0.11 (p <  0.001), respectively. Median ΔPAD was 0.05 [0.01-0.122] was significantly higher in hypometabolic patients exhibiting low Rest Energy Expenditure (p = 0.03). Patients exhibiting ΔPAD > 1% had significantly lower serum albumin level (p = 0.03), and higher nutritional risk (p = 0.02), compared to others. Unlike Nivolumab therapy, there was no increase of PAD after chemotherapy in the same cohort of patients with available scans (n = 45, 25.9 ± 2.9 mm pre-chemotherapy versus 25.7 ± 2.4 mm post-chemotherapy, p = 0.51). Anti-PD-1 treatment was associated with immune-related adverse events in 11 (18.6%) cases including 2 cases of life-threatening acute pulmonary hypertension, both exhibiting post-treatment PAD/AoD ratio > 1.

Conclusion: Nivolumab is associated to PAD enlargement, a potential marker of pulmonary hypertension, sometimes leading to lethal adverse events. Careful CT-scan and echocardiographic evaluation of PAD should be part of the therapeutic work-up of patients receiving Nivolumab, especially those suffering cancer-associated malnutrition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00280-020-04142-9DOI Listing
October 2020

[Fusion transcripts: Therapeutic targets in thoracic oncology].

Bull Cancer 2020 Sep 3;107(9):896-903. Epub 2020 Aug 3.

Université de Paris, faculté de médecine, Paris, France; Centre de recherche des Cordeliers, Team « Inflammation, Complement and Cancer », Inserm, Paris, France; AP-HP Centre, hôpital Cochin, service de génétique et biologie moléculaires, 27, rue du faubourg Saint-Jacques, Paris, France. Electronic address:

Five to ten percent of lung adenocarcinoma harbor chromosomal rearrangements affecting the ALK, ROS1, NTRK and RET genes. These rearrangements are associated with the production of fusion transcripts that lead to the synthesis of chimeric proteins with constitutive kinase activity. These abnormal proteins induce an oncogenic dependency that may be targeted by tyrosine kinase inhibitors. In this review, we will summarize the clinical and molecular epidemiology of chromosomal rearrangements affecting ALK, ROS1, NTRK and RET genes. We will describe the mechanisms of resistance to tyrosine kinase inhibitors that have been reported. We will present the molecular techniques that can be used to detect these rearrangements and the strategies set-up by the molecular oncology laboratories to diagnose these genetic alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2020.05.008DOI Listing
September 2020

Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling.

J Exp Med 2020 11;217(11)

Immunity and Cancer Department, Institut Curie, Paris-Sciences-et-Lettres Research University, Institut National de la Santé et de la Recherche Médicale U932, Paris, France.

Heterozygous missense mutations in coatomer protein subunit α, COPA, cause a syndrome overlapping clinically with type I IFN-mediated disease due to gain-of-function in STING, a key adaptor of IFN signaling. Recently, increased levels of IFN-stimulated genes (ISGs) were described in COPA syndrome. However, the link between COPA mutations and IFN signaling is unknown. We observed elevated levels of ISGs and IFN-α in blood of symptomatic COPA patients. In vitro, both overexpression of mutant COPA and silencing of COPA induced STING-dependent IFN signaling. We detected an interaction between COPA and STING, and mutant COPA was associated with an accumulation of ER-resident STING at the Golgi. Given the known role of the coatomer protein complex I, we speculate that loss of COPA function leads to enhanced type I IFN signaling due to a failure of Golgi-to-ER STING retrieval. These data highlight the importance of the ER-Golgi axis in the control of autoinflammation and inform therapeutic strategies in COPA syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20200600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596811PMC
November 2020

[A step forward for thromboembolic disease treatment in patients with cancer].

Bull Cancer 2020 Jul - Aug;107(7-8):723-725. Epub 2020 Jul 24.

AH-HP, hôpital Cochin, Department of Respiratory Medicine, 75014 Paris, France; Université Paris Descartes, équipe « cancer, immune control and escape », centre de recherches des Cordeliers, Inserm U1138, Paris, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2020.06.001DOI Listing
September 2020

[Surgical management of resectable non-small cell lung cancer: Towards new paradigms].

Bull Cancer 2020 Sep 14;107(9):904-911. Epub 2020 Jul 14.

AP-HP Centre, UNIVERSITE de Paris, hôpital Cochin, service de chirurgie thoracique, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France. Electronic address:

Adapting therapies and providing personalized care for patients with resectable non-small cell lung cancer represent major challenges. This involves integrating several parameters into the patient's management, not only crude pathologic results, but also a better understanding of the mechanisms involved in tumor progression. Many studies have looked at the impact of host and tumor characteristics and their interactions through inflammatory processes or tumor immune environment. Beyond tumor stage, poor nutrition, sarcopenia and inflammatory state have been identified as independent factors that can directly impact postoperative outcome. The development of Enhanced Recovery After Surgery (ERAS), in which patient becomes the main player in their own management, seems to be an interesting answer since it seems to allow a reduction in postoperative complications, length of stay and indirectly reduction in costs. A broader and more complete vision including morphometric evaluation of the patient, physical performances, inflammatory state and nutritional state would provide additional discriminating information which can predict postoperative outcome and help in adapting therapies in a personalized way.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2020.05.010DOI Listing
September 2020

Risk of scleroderma according to the type of immune checkpoint inhibitors.

Autoimmun Rev 2020 Aug 12;19(8):102596. Epub 2020 Jun 12.

Regional Center of Pharmacovigilance, Department of Pharmacology, Cochin Hospital, Paris, France.

Introduction: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). Among them, ICIs-induced systemic sclerosis (SSc) is poorly known.

Methods: To better characterize this irAE, our comprehensive approach combined the description of ICIs-induced scleroderma cases, the systematic review of the literature and the analysis of VigiBase, the WHO pharmacovigilance database.

Results: We identified two cases with underlying limited cutaneous SSc who presented a dramatic increase in the skin thickening following pembrolizumab, associated with scleroderma renal crisis in one case. In the literature, four cases of scleroderma and four cases of morphea have been reported with pembrolizumab or nivolumab. None following ipilimumab, atezolizumab or durvalumab were retrieved. Skin changes appeared or worsened more quickly with pembrolizumab than nivolumab, and had different patterns between both drugs. Patients with generalized skin changes required high-dose prednisone to improve skin thickening. Among the 2527 scleroderma cases identified in VigiBase, 35 were associated with ICIs. Nivolumab and pembrolizumab showed a disproportionality in scleroderma reporting. No disproportionality was found for ipilimumab, atezolizumab or durvalumab.

Conclusion: The risk of scleroderma or fibrosis extension in SSc patients should be considered when initiating anti-PD-1 agents. It suggests the role of PD-1/PD-L1 interaction in the pathophysiology of SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.autrev.2020.102596DOI Listing
August 2020

Outcomes of Patients With Advanced NSCLC From the Intergroupe Francophone de Cancérologie Thoracique Biomarkers France Study by Mutation Subtypes.

JTO Clin Res Rep 2020 Sep 15;1(3):100052. Epub 2020 May 15.

Department of Pneumology, Thoracic Oncology Unit, AP-HP, Groupe Hospitalier HUPC, Hôpital Cochin, Paris, France.

Introduction: mutations are detected in 20% to 30% of NSCLC. However, mutation subtypes may differently influence the outcome of patients with advanced NSCLC.

Methods: In the Biomarkers France study, 4894 mutations (26.2%) were detected in 4634 patients from the 17,664 enrolled patients with NSCLC. Survival and treatment data on noncurative stage III to IV NSCLC were available for 901 patients. First- and second-line treatment effects on progression-free survival and overall survival were analyzed according to the mutations subtype.

Results: Over 95% of patients with mutation were smokers or former smokers who were white (99.5%), presenting with adenocarcinoma (82.5%). The most common mutation subtype was G12C (374 patients; 41.5%), followed by G12V (168; 18.6%), G12D (131; 14.5%), G12A (62; 6.9%), G13C (45; 5.0%), G13D (31; 3.4%), and others (10; 1%). Approximately 21% of patients had transition mutation and 68.2% had a transversion mutation. G12D and transition mutations were predominant in never-smokers. The median overall survival for patients with -mutated NSCLC was 8.1 months (95% confidence interval [CI]: 7.5-9.5), without any differences according to the different subtypes mutations. The median progression-free survival was 4.6 months (95% CI: 4.2-5.1) for first-line treatment and 4.8 months (95% CI: 4.3-6.8) for second-line treatment, without any differences according to the different subtypes mutations.

Conclusions: mutation subtypes influenced neither treatment responses nor outcomes. The G12C mutation was detected in 41.5% of patients, who are now eligible for potent and specific G12C inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtocrr.2020.100052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474404PMC
September 2020

[Lung cancer screening: Nelson study is finally published].

Bull Cancer 2020 Feb;107(2):143-144

AP-HP. Centre - Université de Paris, Hôpital Cochin, Unité d'Oncologie Thoracique, Service de Pneumologie, 75014 Paris, France; Centre de Recherche des Cordeliers, Université de Paris, UMRS 1138 «Complement, Inflammation and Cancer», 75006 Paris, France. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2020.02.003DOI Listing
February 2020

Predictive Value of Soluble PD-1, PD-L1, VEGFA, CD40 Ligand and CD44 for Nivolumab Therapy in Advanced Non-Small Cell Lung Cancer: A Case-Control Study.

Cancers (Basel) 2020 Feb 18;12(2). Epub 2020 Feb 18.

Drug Biology-Toxicology, Cochin Hospital, AP-HP, CARPEM, 75014 Paris, France.

A large interindividual variability has been observed in anti Programmed cell Death 1 (anti-PD1) therapies efficacy. The aim of this study is to assess the correlation of soluble PD-1 (sPD-1), soluble Programmed cell Death Ligand 1 (sPD-L1), Vascular Endothelial Growth Factor A (VEGFA), soluble CD40 ligand (sCD40L) and soluble CD44 (sCD44), with survival in nivolumab-treated metastatic non-small cell lung cancer (NSCLC) patients. Plasma biomarkers were assayed at baseline and after two cycles of nivolumab. A cut-off of positivity for sPD-1, sPD-L1 and sCD40L expressions was defined as a plasma level above the lower limit of quantification. Baseline sPD-1 and sPD-L1 levels were subsequently analyzed in a control group of -mutated () NSCLC patients. Association between survival and biomarkers was investigated using Cox proportional hazard regression model. Eighty-seven patients were included (51 nivolumab-treated patients, 36 in EGFR-mutated group). In nivolumab group, baseline sPD-1, sPD-L1 and sCD40L were positive for 15(29.4%), 27(52.9%) and 18(50%) patients, respectively. We defined a composite criteria (sCombo) corresponding to sPD-1 and/or sPD-L1 positivity for each patient. In nivolumab group, baseline sCombo positivity was associated with shorter median progression-free survival (PFS) (78 days 95%CI (55-109) vs. 658 days (222-not reached); HR: 4.12 (1.95-8.71), = 0.0002) and OS (HR: 3.99(1.63-9.80), = 0.003). In multivariate analysis, baseline sCombo independently correlated with PFS (HR: 2.66 (1.17-6.08), = 0.02) but not OS. In EGFR-mutated group, all patients were baseline sCombo positive; therefore this factor was not associated with survival. After two cycles of nivolumab, an increased or stable sPD-1 level independently correlated with longer PFS (HR: 0.49, 95%CI (0.30-0.80), = 0.004) and OS (HR: 0.39, 95%CI (0.21-0.71), = 0.002). VEGFA, sCD40L and sCD44 did not correlate with survival. We propose a composite biomarker using sPD-1and sPDL-1 to predict nivolumab efficacy in NSCLC patients. A larger validation study is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12020473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072584PMC
February 2020

[2019 international oncology news: A compendium].

Bull Cancer 2020 Feb 10;107(2):148-156. Epub 2020 Feb 10.

Centre hospitalier universitaire Giscard d'Estaing, service thérapie cellulaire et hématologie clinique, 58, rue Montalembert, 63000 Clermont Ferrand, France.

Over the past years, planet oncology has kept changing and moving forward. Recent results of important clinical trials are challenging our daily practices. With modesty, the Editorial Board of BulletinduCancer has selected some clinical trials they consider as "must-know about" even if they go beyond our medical fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2020.01.010DOI Listing
February 2020

Efficacy of Immune Checkpoint Inhibitors in Lung Sarcomatoid Carcinoma.

J Thorac Oncol 2020 05 25;15(5):860-866. Epub 2020 Jan 25.

Department of Thoracic Oncology, AP-HP, Groupe Hospitalier HUPC, Hôpital Cochin, Paris, France; Centre de Recherche des Cordeliers, Université Paris Descartes, Complement, Inflammation and Cancer, Paris, France. Electronic address:

Introduction: Immune checkpoint inhibitors (ICIs) have improved cancer prognosis but have not been evaluated specifically in sarcomatoid carcinoma (SC), a rare lung cancer subtype with poor prognosis. As such, our study sought to retrospectively assess the efficacy of ICI in SC.

Methods: All consecutive patients with centrally confirmed SC treated using ICI as a second-line treatment or beyond between 2011 and 2017 were enrolled. Programmed death-ligand 1 (PD-L1) tumor expression was assessed using immunohistochemistry (SP263 clone) and the tumor mutational burden (TMB) with the Foundation One panel. TMB was considered high if it was greater than or equal to 10 mutations per megabase.

Results: Overall, 37 patients with SC were evaluated, predominantly men (73%) with a median age of 63.2 years (36.8-79.7) and who were current or former smokers (94.6%). Immunotherapy (nivolumab, 86.5% of cases) was given as a second-line treatment in 54% of the patients and as third-line treatment or beyond in 46% of the patients. The objective response rate was 40.5% and disease control rate was 64.8%, regardless of PD-L1 status. Median overall survival was 12.7 months (range: 0.3-45.7). One-third of patients exhibited early progression. The median PD-L1 expression was 70% (0-100). There was a trend toward higher PD-L1 expression in responsive diseases, with an objective response rate of 58.8% in patients with PD-L1+ and 0% in the one patient with PD-L1- (p = 0.44). The median TMB was 18 (4-39) mutations per megabase, with 87.5% of the cases displaying a high TMB. There was a trend toward higher TMB in responders versus stable or progressive diseases (p = 0.2).

Conclusions: Patients with SC exhibited high response rates and prolonged overall survival under ICI treatment. These data support the prospective investigation of ICI in patients with SC who are under first-line treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtho.2020.01.014DOI Listing
May 2020

Pre-Disease and Pre-Surgery BMI, Weight Loss and Sarcopenia Impact Survival of Resected Lung Cancer Independently of Tumor Stage.

Cancers (Basel) 2020 Jan 22;12(2). Epub 2020 Jan 22.

Thoracic Surgery Department, Paris Center University Hospitals, AP-HP, 75014 Paris, France.

Lower pre-surgery Body Mass Index (BMI) and low muscle mass impact negatively long-term survival of non-small cell lung cancer (NSCLC). We investigated their influence on survival after major lung resection for NSCLC.

Methods: A retrospective analysis of a prospectively collected database was made on 304 consecutive patients.

Results: Underweight, normal, overweight and obese patients represented 7.6%, 51.6%, 28.6%, and 12.6% of the pre-disease population. Weight loss and gain were recorded in 5% and 44.4% of patients, respectively. Low muscle mass was more frequently associated with BMI < 25 kg/m ( < 0.000001). Overall survival was positively affected by pre-disease ( = 0.036) and pre-surgery ( 0.017) BMI > 25 kg/m, and, even more, in case of BMI > 25 kg/m and increasing weight ( = 0.012). Long-term outcome was negatively influenced by low muscle mass ( = 0.042) and weight loss ( 0.0052) as well as age ( 0.017), ASA categories ( 0.025), extent of resection ( 0.0001), pleural invasion ( 0.0012) and higher pathologic stage ( < 0.0001). Three stepwise multivariable models confirmed the independent favorable prognostic value of higher pre-disease (RR 0.66[0.49-0.89], 0.006) and pre-surgery BMI (RR 0.72[0.54-0.98], 0.034), and the absence of low muscle mass (RR 0.56[0.37-0.87], 0.0091).

Conclusions: Body reserves assessed by simple clinical markers impact survival of surgically treated NSCLC. Strategies improving body fat and muscular mass before surgery should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12020266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072703PMC
January 2020

[SMARCA4-deficient thoracic tumors: A new entity].

Bull Cancer 2020 Jan 6;107(1):41-47. Epub 2020 Jan 6.

Cordeliers Research Center, « Immune Control and Escape », unité Inserm UMRS 1138, Paris, France; AP-HP, Université Paris Descartes, hôpital Cochin, département de pathologie, service d'anatomie pathologique, HUPC, 27, rue du faubourg Saint-Jacques, 74014 Paris, France. Electronic address:

A growing number of studies suggest a tumor suppressor role for the SWI/SNF complex involved in the remodeling of chromatin. Alterations of this complex have been found in many tumors of different origins, with topographic, morphologic and phenotypic diversity. Notably, they define 2 types of thoracic tumors: SMARCA4-deficient non-small cell lung carcinoma and SMARCA4-deficient sarcoma. Some clinical features appear to be common to both, such as intrathoracic localization, smoking exposure, male predominance and poor prognosis. However, the histological distinction between these two entities is sometimes difficult and it is not excluded that these entities belong to the same tumor spectrum with different degrees of differentiation. The therapy of these tumors is not yet codified. These tumors do not seem associated with oncogenic driver mutations allowing the prescription of targeted therapy, but immunotherapy has been shown to be effective in rare reported cases. More specific treatments using EZH2 inhibitors also seem promising in SMARCA4 deficient sarcomas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bulcan.2019.12.001DOI Listing
January 2020

The impact of body composition parameters on severe toxicity of nivolumab.

Eur J Cancer 2020 01 30;124:170-177. Epub 2019 Nov 30.

Department of Medical Oncology, Cochin Hospital, AP-HP 5, CARPEM, CERTIM, Paris, France; Laboratory of Biological Nutrition EA, Pharmacy University, Université Paris Descartes, 4466, Paris, France.

Background: The occurrence of severe, acute limiting toxicity in patients receiving anti-programmed cell death receptor-1 monoclonal antibodies, such as nivolumab, is largely unpredictable. Sarcopenia was found to be associated with anti-cytotoxic T-lymphocyte-associated protein 4 acute toxicity. We explore the clinical and pharmacological parameters influencing nivolumab toxicity, including body composition.

Methods: From June 2015 to January 2017, all consecutive patients treated with nivolumab in our institution were prospectively included. We studied the relationship between muscle mass assessed by computed tomography, nivolumab trough level (C) at day 14 assessed using the enzyme-linked immunosorbent assay method, and the occurrence of immune grade III or IV toxicity or any toxicity leading to treatment discontinuation (immune-related acute limiting toxicity [irALT]).

Results: In our population (n = 92) with a majority of lung cancer (72%), forty-five (51.7%) patients were sarcopenic. The median plasma nivolumab C at day 14 was 15.4 μg/mL (interquartile range = 11.8-21.0). In multivariate analysis, hypoalbuminaemia (<35 g/L) was independently associated with low nivolumab C on day 14 (odds ratio [OR] = 0.09; 95% confidence interval [CI] = 0.01-0.59, p = 0.01) and overweight/obesity with high nivolumab C on day 14 (OR = 5.94; 95% CI = 1.25-28.29, p = 0.03). We observed 22 irALTs in 19 patients (21%). The most frequent irALT was respiratory (6.5%) disorders and gastrointestinal (4.3%) disorders. Patients with sarcopenia were at significantly increased risk of experiencing an irALT (OR = 3.84; 95% CI = 1.02-14.46, p = 0.047). No association was found between toxicity and nivolumab plasma C at day 14.

Conclusions: Our results highlight the importance of assessing body composition and suggest that sarcopenia could predict severe immune-related toxicity of nivolumab in real life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2019.11.003DOI Listing
January 2020

Is there an Exposure-Response Relationship for Nivolumab in Real-World NSCLC Patients?

Cancers (Basel) 2019 Nov 13;11(11). Epub 2019 Nov 13.

Department of Pharmacokinetics and Pharmacochemisty, Cochin Hospital, AP-HP, CARPEM, 75014 Paris, France.

Pharmacokinetic/pharmacodynamic data from real-world cohort are sparse in non small-cell lung cancer (NSCLC) patients treated with nivolumab. The aim of this prospective observational study was to explore the exposure-response relationship for effectiveness and toxicity of nivolumab in 81 outpatients with metastatic lung cancer. Nivolumab plasma trough concentrations (Cmin) were assayed at days 14, 28, and 42. Prognostic factors (including Cmin) regarding progression-free survival (PFS) and overall survival (OS) were explored using a multivariate Cox model. A Spearman's rank test was used to investigate the relationship between Cmin and grade >2 immune-related adverse events (irAE). Mean nivolumab Cmin was 16.2 ± 6.0 µg/mL ( = 76), 25.6 ± 10.2 µg/mL ( = 64) and 33.4 ± 11.3 µg/mL ( = 53) at days 14, 28, and 42, respectively. No pharmacokinetic/pharmacodynamic (PK/PD) relationship was observed with either survival or onset of irAE. Multivariable Cox regression analysis identified Eastern Cooperative Oncology Group Performance Status (hazard ratio 1.85, 95%confidence interval 1.02-3.38, -value = 0.043) and baseline use of corticosteroids (HR 8.08, 95%CI 1.78-36.62, -value = 0.007) as independent risk factor for PFS and only baseline use of corticosteroids (HR 6.29, 95%CI 1.46-27.08, -value = 0.013) for OS. No PK/PD relationship for nivolumab was observed in real-world NSCLC patients. This supports the recent use of flat dose regimens without plasma drug monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11111784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895963PMC
November 2019
-->