Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial

Immunotherapy; Thymic carcinoma; ThymomaImmunoteràpia; Carcinoma tímic; TimomaInmunoterapia; Carcinoma tímico; TimomaBackground Thymic malignancies are rare intrathoracic tumors, which may be aggressive and difficult to treat. They represent a therapeutic challenge in the advanced/metastatic setting, with limited treatment options after the failure of first-line platinum-based chemotherapy. They are frequently associated with autoimmune disorders that also impact oncological management. Materials and methods NIVOTHYM is an international, multicenter, phase II, two-cohort, single-arm trial evaluating the activity and safety of nivolumab [240 mg intravenously (i.v.) q2 weeks] alone or with ipilimumab (1 mg /kg i.v. q6 weeks) in patients with advanced/relapsed type B3 thymoma or thymic carcinoma, after exposure to platinum-based chemotherapy. The primary endpoint is progression-free survival rate at 6 months (PFSR-6) based on RECIST 1.1 as per independent radiological review. Results From April 2018 to February 2020, 55 patients were enrolled in 15 centers from 5 countries. Ten patients (18%) had type B3 thymoma and 43 (78%) had thymic carcinoma. The majority were male (64%), and the median age was 58 years. Among the 49 eligible patients who started treatment, PFSR-6 by central review was 35% [95% confidence interval (CI) 22% to 50%]. The overall response rate and disease control rate were 12% (95% CI 5% to 25%) and 63% (95% CI 48% to 77%), respectively. Using the Kaplan–Meier method, median progression-free survival and overall survival by local assessment were 6.0 (95% CI 3.1-10.4) months and 21.3 (95% CI 11.6-not estimable) months, respectively. In the safety population of 54 patients, adverse events (AEs) of grade 1/2 were observed in 22 (41%) patients and grade 3/4 in 31 (57%) patients. Treatment-related AEs of grade 4 included one case of neutropenia, one case of immune-mediated transaminitis, and two cases of myocarditis. Conclusions Nivolumab monotherapy demonstrated an acceptable safety profile and objective activity, although it has been insufficient to meet its primary objective. The second cohort of NIVOTHYM is currently ongoing to assess the combination of nivolumab plus ipilimumab

Wegener Granulomatosis Revealed by Pleural Effusion

Pulmonary signs are common in Wegener's granulomatosis (WG). However, an initial presentation including pleural effusion has not been described. We describe a case of WG in which pleural effusion was the first clinical manifestation. A 45-year-old man with dorsal pain presented with pleural thickening and effusion, and a visible nodule on a thoracic scan. A dense chronic inflammatory infiltrate was obtained by pleural biopsy and an open lung biopsy revealed necrotizing granulomatous vasculitis. Serologies were positive for antineutrophil cytoplasmic antibodies and antiproteinase 3 antibodies. A diagnosis of WG was conducted and the patient was started on cyclophosphamide and methylprednisolone as an initial treatment, with a favorable evolution. Although pleural effusion is rarely described in WG, this pathology must be considered in the presence of this clinical manifestation

Influence of neutropenia on mortality of critically ill cancer patients : results of a meta-analysis on individual data

Background: The study objective was to assess the influence of neutropenia on outcome of critically ill cancer patients by meta-analysis of individual data. Secondary objectives were to assess the influence of neutropenia on outcome of critically ill patients in prespecified subgroups (according to underlying tumor, period of admission, need for mechanical ventilation and use of granulocyte colony stimulating factor (G-CSF)). Methods: Data sources were PubMed and the Cochrane database. Study selection included articles focusing on critically ill cancer patients published in English and studies in humans from May 2005 to May 2015. For study selection, the study eligibility was assessed by two investigators. Individual data from selected studies were obtained from corresponding authors. Results: Overall, 114 studies were identified and authors of 30 studies (26.3% of selected studies) agreed to participate in this study. Of the 7515 included patients, three were excluded due to a missing major variable (neutropenia or mortality) leading to analysis of 7512 patients, including 1702 neutropenic patients (22.6%). After adjustment for confounders, and taking study effect into account, neutropenia was independently associated with mortality (OR 1.41; 95% CI 1.23-1.62; P = 0.03). When analyzed separately, neither admission period, underlying malignancy nor need for mechanical ventilation modified the prognostic influence of neutropenia on outcome. However, among patients for whom data on G-CSF administration were available (n = 1949; 25.9%), neutropenia was no longer associated with outcome in patients receiving G-CSF (OR 1.03; 95% CI 0.70-1.51; P = 0.90). Conclusion: Among 7512 critically ill cancer patients included in this systematic review, neutropenia was independently associated with poor outcome despite a meaningful survival. Neutropenia was no longer significantly associated with outcome in patients treated by G-CSF, which may suggest a beneficial effect of G-CSF in neutropenic critically ill cancer patients

Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids

International audienceThe worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary car-cinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low-and high-grade lung neuroendocrine neoplasms

Déterminants de la prise en charge et du pronostic des cancers broncho-pulmonaires hospitalisés

In patients with advanced lung cancer non-eligible for curative treatment, the goal of care is not healing but improving symptoms and survival. The prognosis is related to patient and tumor characteristics, response to chemotherapy and its overall management decided jointly with the medical team, the patient and his family. It is therefore necessary to assess early these prognostic factors to optimize the risk-benefit ratio of treatment undertaken.As part of this work, ethical, clinical and laboratory determinants of management and prognosis of locally advanced or metastatic lung cancer patients were investigated. In the first part, the prognosis' determinants of patients treated with chemotherapy (« Pharmacogenoscan-poumon » study) were studied: association between the level of expression of protein biomarkers and tumor response to chemotherapy and assessment of interest of tumor response according to RECIST criteria. We have, in the second part, analyzed the factors influencing the management and prognosis of lung cancer patients developing organ failure. Three situations were described: patients at the time of the development of this organ failure, lung cancer patients admitted to intensive care units, the overall population and only those carrying an oncogenic mutation.Chez les patients porteurs d'un cancer bronchique avancé non éligible à un traitement curatif, l'objectif du traitement n'est pas la guérison mais le soulagement des symptômes et l'amélioration de la survie. Le pronostic est lié aux caractéristiques du patient et de la tumeur, à la réponse tumorale après chimiothérapie et à la prise en charge globale décidée conjointement avec l'équipe médicale, le patient et son entourage. Il convient donc d'évaluer précocement ces facteurs pronostiques pour optimiser le rapport bénéfice-risque des traitements entrepris, dans le cadre des thérapeutiques anti-cancéreuses ou de façon plus globale.Dans le cadre de ce travail, des déterminants éthiques, cliniques et paracliniques de la prise en charge et du pronostic des patients porteurs d'un cancer bronchique localement avancé ou métastatique ont été recherchés. Dans une 1ère partie, les déterminants du pronostic de patients traités par chimiothérapie (étude « Pharmacogenoscan-poumon ») ont été étudiés : association entre le niveau d'expression de biomarqueurs tumoraux protéiques et la réponse à la chimiothérapie et intérêt de l'évaluation de la réponse tumorale selon les critères RECIST. Nous avons, dans une seconde partie, analysé les éléments influençant la prise en charge et le pronostic de patients porteurs d'un cancer bronchique développant une défaillance d'organe. Trois situations ont été décrites : celle de patients dès l'apparition de cette défaillance d'organe, celle de l'ensemble des patients porteurs d'un cancer bronchique admis en réanimation, et uniquement de ceux porteurs d'une mutation tumorale oncogénique

Determinants of management and prognosis of hospitalized lung cancer patients

Chez les patients porteurs d'un cancer bronchique avancé non éligible à un traitement curatif, l'objectif du traitement n'est pas la guérison mais le soulagement des symptômes et l'amélioration de la survie. Le pronostic est lié aux caractéristiques du patient et de la tumeur, à la réponse tumorale après chimiothérapie et à la prise en charge globale décidée conjointement avec l'équipe médicale, le patient et son entourage. Il convient donc d'évaluer précocement ces facteurs pronostiques pour optimiser le rapport bénéfice-risque des traitements entrepris, dans le cadre des thérapeutiques anti-cancéreuses ou de façon plus globale.Dans le cadre de ce travail, des déterminants éthiques, cliniques et paracliniques de la prise en charge et du pronostic des patients porteurs d'un cancer bronchique localement avancé ou métastatique ont été recherchés. Dans une 1ère partie, les déterminants du pronostic de patients traités par chimiothérapie (étude « Pharmacogenoscan-poumon ») ont été étudiés : association entre le niveau d'expression de biomarqueurs tumoraux protéiques et la réponse à la chimiothérapie et intérêt de l'évaluation de la réponse tumorale selon les critères RECIST. Nous avons, dans une seconde partie, analysé les éléments influençant la prise en charge et le pronostic de patients porteurs d'un cancer bronchique développant une défaillance d'organe. Trois situations ont été décrites : celle de patients dès l'apparition de cette défaillance d'organe, celle de l'ensemble des patients porteurs d'un cancer bronchique admis en réanimation, et uniquement de ceux porteurs d'une mutation tumorale oncogénique.In patients with advanced lung cancer non-eligible for curative treatment, the goal of care is not healing but improving symptoms and survival. The prognosis is related to patient and tumor characteristics, response to chemotherapy and its overall management decided jointly with the medical team, the patient and his family. It is therefore necessary to assess early these prognostic factors to optimize the risk-benefit ratio of treatment undertaken.As part of this work, ethical, clinical and laboratory determinants of management and prognosis of locally advanced or metastatic lung cancer patients were investigated. In the first part, the prognosis' determinants of patients treated with chemotherapy (« Pharmacogenoscan-poumon » study) were studied: association between the level of expression of protein biomarkers and tumor response to chemotherapy and assessment of interest of tumor response according to RECIST criteria. We have, in the second part, analyzed the factors influencing the management and prognosis of lung cancer patients developing organ failure. Three situations were described: patients at the time of the development of this organ failure, lung cancer patients admitted to intensive care units, the overall population and only those carrying an oncogenic mutation

Use of Intensive Care in Patients with Nonresectable Lung Cancer

Contexte : L admission des patients porteurs d un cancer broncho-pulmonaire (CBP) en réanimation a été critiquée. Nous avons évalué si l admission de ces patients en réanimation améliorait leur survie à 3 mois. Les facteurs associés à la survie ont été identifiés. Méthodes : Etude rétrospective de patients porteurs d un CBP non résécable admis consécutivement dans trois services de réanimation en France (2000-2007, 2005-2007, et 2005-2006, respectivement). Resultats : Nous avons inclus 103 patients avec un SAPS médian [Q1-Q3] de 33 [25-46] et un LOD score médian de 3 [1-4]. Le recours à la ventilation mécanique invasive a été nécessaire pour 41 (40%) patients. Soixante trois (61%) patients étaient métastatiques et 26 (25%) avaient un ECOG performance status (PS) >2. Le motif d admission en réanimation était une détresse respiratoire aiguë pour 58 (56%) patients. Le taux de survie à 3 mois était de 37% (intervalle de confiance à 95% [IC 95%], 28-46). En analyse multivariée, les variables associées à la mortalité étaient un ECOG-PS >2 (hazard ratio [HR], 2.65; IC 95%, 1.43-4.88), l existence de métastases à l admission (HR, 1.90; IC 95%, 1.08-3.33), et un LOD score élevé (HR, 1.19; IC 95%, 1.08-1.32). La décroissance du LOD score au cours des 72 premières heures était corrélée à la survie. Conclusions : La survie des patients porteurs d un CBP non résécable admis en réanimation était de 37% après 90 jours. Nos résultats apportent un argument supplémentaire selon lequel la prise en charge en réanimation pour des patients porteurs d un CBP non résécable avec des dysfonctions d organe peut être légitime.Background: Admission of lung cancer patients to the intensive care unit (ICU) has been criticized. We evaluated whether ICU admission improved 3-month survival in patients with nonresectable lung cancer. Factors associated with survival were identified. Methods: Retrospective study in consecutive non-surgical lung cancer patients admitted to three ICUs in France (2000-2007, 2005-2007, and 2005-2006, respectively). Results: We included 103 patients with a median [Q1-Q3] SAPS II of 33 [25-46] and a median LOD of 3 [1-4]. Invasive mechanical ventilation was required in 41 (40%) patients. Sixty-three (61%) patients had metastasis and 26 (25%) an ECOG performance status (PS) >2. The reason for ICU admission was acute respiratory failure in 58 (56%) patients. Three-month survival rate was 37% (95% confidence interval [95% CI], 28-46). By multivariate analysis, variables associated with mortality were ECOG-PS >2 (hazard ratio [HR], 2.65; 95% CI, 1.43-4.88), metastasis at admission (HR, 1.90; 95% CI, 1.08-3.33), and worse LOD score (HR, 1.19; 95% CI, 1.08-1.32). The LOD score decrease over the first 72 hours was associated with survival. Conclusions: Survival in patients with non-surgical lung cancer requiring ICU admission was 37% after 90 days. Our results provide additional evidence that ICU management may be appropriate in patients with nonresectable lung cancer and organ failures.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Advances and Therapeutic Perspectives in Extended-Stage Small-Cell Lung Cancer

Extended small cell lung cancer (ED-SCLC) is a very aggressive disease, characterized by rapid growth and an early tendency to relapse. In contrast to non-small cell lung cancer, no therapeutic innovation has improved survival in patients with ED-SCLC over the past 20 years. Recently, immunotherapy has shown an important role in the management of these patients, emerging as the treatment of first choice in combination with chemotherapy and completely changing the therapeutic paradigm. However, patients’ selection for this strategy is still challenging due to a lack of reliable predictive biomarkers. Conversely, the immunotherapy efficacy beyond the first line is pretty disappointing and innovative chemotherapies or target agents seem to be more promising in this setting. Some of them are also under evaluation as an upfront strategy and they will probably change the treatment algorithm in the next future. This proposal provides a comprehensive overview of available treatment strategies for ED-SCLC patients, highlighting their strengths and weaknesses