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Objectives Immune checkpoint inhibitors have become the standard of care for metastatic non–small-cell lung cancer (NSCLC) progressing during or after platinum-based chemotherapy. Real-world clinical practice tends to represent more diverse patient characteristics than randomized clinical trials. We sought to evaluate overall survival (OS) outcomes in the total study population and in key subsets of patients who received nivolumab for previously treated advanced NSCLC in real-world settings in France, Germany, or Canada. Materials and methods Data were pooled from two prospective observational cohort studies, EVIDENS and ENLARGE, and a retrospective registry in Canada. Patients included in this analysis were aged ≥18 years, had stage IIIB/IV NSCLC, and received nivolumab after at least one prior line of systemic therapy. OS was estimated in the pooled population and in various subgroups using the Kaplan-Meier method. Timing of data collection varied across cohorts (2015–2019). Results Of the 2585 patients included in this analyses, 1235 (47.8 %) were treated in France, 881 (34.1 %) in Germany, and 469 (18.1 %) in Canada. Median OS for the total study population was 11.3 months (95 % CI: 10.5–12.2); this was similar across France, Germany, and Canada. The OS rate was 49 % at 1 year and 28 % at 2 years for the total study population. In univariable Cox analyses, the presence of epidermal growth factor receptor mutations in nonsquamous disease, liver, or bone metastases were associated with significantly shorter OS, whereas tumor programmed death ligand 1 expression and Eastern Cooperative Oncology Group performance status 0–1 were associated with significantly prolonged OS. Similar OS was noted across subgroups of age and prior lines of therapy. Conclusion OS rates in patients receiving nivolumab for previously treated advanced NSCLC in real-world clinical practice closely mirrored those in phase 3 studies, suggesting similar effectiveness of nivolumab in clinical trials and clinical practice.

Aim: We performed a clinical audit of the management of patients with EGFR mutations, 1 year after the introduction of EGFR tyrosine kinase inhibitor ( EGFR-TKI) in first-line treatment. Methods: Compliance was defined by tumor molecular profiling for stage IIIB and IV non-small-cell lung cancer and first-line treatment as recommended by the French guidelines. Results: Among the 169 EGFR-mutated patients, compliance was 76.4%. The most common noncompliance criterion was chemotherapy given in first-line treatment instead of EGFR-TKI. No dedicated multidisciplinary meeting and type of institutions were independent unfavorable predictors for compliance. Compliance to guidelines was significantly correlated with time-to-first subsequent treatment improvement (2.5 vs 9.1 months; p

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.

Introduction L’etude EVIDENS vise a evaluer l’efficacite et la tolerance du nivolumab utilise en conditions de vie reelle en France chez des pts atteints de cancer du poumon et a decrire leurs caracteristiques cliniques et leur qualite de vie. Methodes EVIDENS est une etude de cohorte observationnelle multicentrique et longitudinale incluant des pts adultes atteints de cancer du poumon traites par nivolumab d’octobre 2016 a novembre 2017. La survie depuis l’initiation du traitement a ete evaluee par la methode de Kaplan–Meier et la qualite de vie par le questionnaire EQ-5D-3L. Resultats Au total, 1462 patients atteints de cancer du poumon ont ete inclus dans 146 centres francais. Les caracteristiques des patients et de la tumeur a l’inclusion des 1394 pts atteints de cancer bronchique non a petites cellules (CBNPC) etaient representatives d’une population standard de pts atteints d’un CBNPC avance : âge median : 66 ans, homme : 69,2 %, indice de performance de 0–1 : 83,2 %, maladie de stade IV : 91,3 %, histologie epidermoide : 31,1 % [1] . Des metastases cerebrales etaient presentes chez 20,0 % des patients. Nivolumab a ete principalement administre en 2e ligne (74 %). La mediane de survie sans progression et de survie globale etait respectivement de 2,8 mois [IC95 % : 2,6–3,0] et 10 mois [IC95 % : 9,2–11,0]. Des evenements indesirables ont ete rapportes chez 440 patients (31,6 %), dont 98 patients (7,0 %) ont presente des evenements de grade 3–4. Par ailleurs, une amelioration du changement moyen sur l’echelle visuelle analogique de qualite de vie par rapport a l’inclusion etait statistiquement significative a 9 et 12 mois et une difference minimale importante a ete atteinte a 12 mois pour la population epidermoide [2] . L’analyse presentee pendant le congres inclura des donnees actualisees sur l’efficacite, la securite et la qualite de vie, ainsi que des sous-groupes d’interet (metastases cerebrales, âge, radiotherapie prealable) apres un suivi minimum de 17 mois. Conclusion A ce jour, EVIDENS est la plus grande etude observationnelle prospective evaluant le nivolumab chez des patients atteints d’un cancer du poumon et confirme l’efficacite et la securite du medicament en vraie vie. Cette analyse fournira de nouvelles informations sur l’experience clinique avec le nivolumab grâce a un suivi plus long et pour la premiere fois dans des sous-groupes cliniquement pertinents.

Introduction Les metastases cerebrales (MC) dans les cancers bronchiques non a petites cellules (CBNPC) sont associees a un mauvais pronostic et a une resistance au traitement systemique. La caracterisation du micro-environnement immunitaire des MC permettrait de fournir un rationnel a l’utilisation de l’immunotherapie et d’aider a l’identification de nouvelles cibles therapeutiques. Methodes Quatre-vingt-cinq MC de CBNPC avances naifs de tout traitement et 14 tumeurs primaires pulmonaires appariees ont ete collectees. L’expression de 770 genes impliques dans la reponse immunitaire etait evaluee par le panel PanCancer IO360 (NanoString Technologies, Inc). Les donnees etaient comparees entre MC et tumeurs primitives. La reponse objective aux anti-PD1 etait evaluee selon les criteres RECIST 1.1. Resultats L’environnement immunitaire tumoral des MC etait plus « froid » comparativement aux CBNPC primitifs, avec 92 % des MC dans le cluster « froid » et 58 % des tumeurs primaires dans le cluster « chaud ». L’expression de genes caracterisant les differents types de cellules immunitaires etaient reprimes dans les MC par rapport aux tumeurs primitives, notamment pour les lymphocytes B (−1,7 log2 FC, p Conclusion Le micro-environnement immunitaire est moins favorable a l’efficacite des anti-PD1 dans les MC que dans les tumeurs primitives. La chimiokine CCL21 pourrait etre une nouvelle cible therapeutique dans les MC des CBNPC.

Introduction Les mutations activatrices du gene human epidermal growth factor receptor-2 (HER2) concerne 1,6 a 4,2 % des adenocarcinomes pulmonaires et sont majoritairement des insertions de l’exon 20. L’objectif de cette etude etait d’evaluer le microenvironnement immun et l’efficacite des anti-PD-1, mal connus dans ce sous-groupe moleculaire. Methodes Tous les cancers bronchiques non a petites cellules mutes HER2 (CBNPC HER2 +) diagnostiques par la plateforme de biologie moleculaire des Hospices Civils de Lyon (HCL) entre 2010 et 2019 ont ete inclus. Les donnees cliniques, histologiques, moleculaires et l’efficacite des anti-PD-1 ont ete collectees retrospectivement. Des immunomarquages PD-L1 ont ete realises sur les prelevements disponibles. Une cohorte controle de 225 patients CBNPC HER2 - traites par anti-PD-1 aux HCL de 2015 a 2019 apres echec d’une chimiotherapie a ete constituee. Les taux de reponses objectives aux anti-PD-1 selon RECIST 1.1 (test de Fisher), la survie sans progression (SSP) et globale (SG) (log rank) avec les anti-PD-1 etaient compares entre CBNPC HER2 + et − . Resultats Cinquante-trois CBNPC HER2 + etaient inclus : 55 % de femmes, 57 % de non-fumeurs, âge median 66 ans (45-88), 70 % de stade IV. Tous etaient des adenocarcinomes. Une expression de PD-L131 % des cellules tumorales etaient retrouvees dans 40 % des cas (16/40), 350 % dans 10 % (4/40). 11 CBNPC HER2 + ont recus un anti-PD-1 en deuxieme ligne et plus avec pour meilleure reponse une reponse partielle (RP) dans 9 % (1/11) des cas, une stabilite (ST) dans 46 % (5/11), une progression (PR) dans 45 % (5/11). La SSP mediane sous anti-PD-1 etait de 3,6 mois, la SG mediane de 5,8 mois. Dans la cohorte controle, la meilleure reponse aux anti-PD-1 etait une RP dans 7,5 % des cas, une ST dans 31 %, une PR dans 61 %, pour une SSP mediane de 2 mois et une SG mediane de 7,1 mois. Les taux de reponse (p = 0,22), la SSP (p = 0,59) et la SG (p = 0,66) n’etaient pas statistiquement differents entre les deux cohortes. Les taux de reponses, la SSP et la SG n’etaient pas statistiquement differents en comparant les CBNPC HER2 + et les CBNPC KRAS + ou pan-sauvage de la cohorte controle. 2 CBNPC HER2 + ont recu un anti-PD-1 en premiere ligne (PD-L1350 %) avec 2 RP, PFS a 7,75 mois et RP toujours en cours apres 9,5 mois de traitement, respectivement. Conclusion L’expression de PD-L1 est faible dans les CBNPC HER2+. Cependant, l’efficacite des anti-PD-1 semble comparable entre CBNPC HER2+ et CBNPC HER2−.

Introduction Le nivolumab a demontre un benefice en survie globale (SG) chez les patients pretraites avec un cancer bronchopulmonaire non a petites cellules (CBNPC) avance dans deux etudes randomisees de phase III. Methodes EVIDENS est une etude observationnelle francaise multicentrique longitudinale ayant inclus entre decembre 2016 et novembre 2017 des patients atteints d’un cancer bronchopulmonaire et traites par nivolumab. Nous rapportons ici les resultats d’une analyse intermediaire avec une duree de suivi minimum de 8 mois. La SG et la survie sans progression (SSP) ont ete estimees a l’aide de la methode de Kaplan–Meier. Resultats L’etude EVIDENS a inclus 1394 patients atteints d’un CBNPC avance et ayant recu au moins une injection de nivolumab. Les sous-types histologiques epidermoides et non-epidermoides concernaient respectivement 31,1 % et 68,9 % des patients. Les caracteristiques des patients a l’inclusion etaient representatives de la population standard de patients atteints d’un CBNPC avance : 66,0 ans d’âge median, 69,2 % d’hommes, 89,6 % de fumeurs actuels ou anciens fumeurs et 83,2 % ayant un PS 0–1. Des metastases cerebrales et des maladies auto-immunes actives ont ete respectivement decrites chez 20,0 % et 2,9 % des patients a l’initiation du traitement. L’expression de PD-L1 a ete evaluee chez 18,9 % des patients et 63,6 % d’entre eux avaient une tumeur consideree comme positive (≥ 1 % des cellules tumorales ou immunitaires positives). La recherche d’une mutation de l’EGFR a ete effectuee chez 91 % des patients presentant une tumeur non-epidermoide, et rapportee chez 5,6 % d’entre eux. Nivolumab a ete administre en 2e et 3e ligne ou plus respectivement pour 74,0 % et 25,4 % des patients. Le nombre median d’injections etait de 5. La mediane de SSP etait de 2,8 mois et la mediane de SG estimee a 10 mois. A 6 mois, le taux de SSP etait de 30,5 %, le taux de SG de 65,3 % et le meilleur taux de reponse objective de 16,5 %. Des evenements indesirables ont ete decrits chez 30,9 % des patients traites et 7,0 % ont presente au moins un grade 3 ou 4. Les evenements indesirables d’origine immunologique ont ete decrits chez 12,4 % des patients traites et 1,5 % ont presente au moins un grade 3 ou 4. Les arrets de traitement pour cause de toxicite ont ete rapportes chez 4,6 % des patients. Conclusion Les resultats preliminaires d’EVIDENS confirment en vie reelle le profil de tolerance et l’efficacite du nivolumab administre dans les centres francais chez des patients presentant un cancer bronchopulmonaire.

Introduction Le nivolumab est un anti-PD1 disponible en France depuis janvier 2015, dans le cadre d’une autorisation temporaire d’utilisation (ATU) puis de l’autorisation de mise sur la marche (AMM), a partir de la 2e ligne de traitement du CBNPC localement avance ou metastatique. A ce jour, peu de donnees sont disponibles en vie reelle. Methodes EVIDENS est une etude observationnelle francaise multicentrique longitudinale qui vise a inclure pres de 1300 patients traites par nivolumab pour un CBNPC avance. L’objectif principal est de decrire les caracteristiques sociodemographiques et cliniques des patients a l’initiation du nivolumab et d’estimer la survie globale a 3 ans dans la population globale et par sous-type histologique. Les objectifs secondaires sont d’evaluer a 1, 2 et 3 ans la survie globale, la survie sans progression, le taux de reponse objective, l’evolution de la qualite de vie ainsi que l’incidence, la gravite et la prise en charge des effets indesirables. L’evaluation de la reponse est faite par l’investigateur. Resultats Au 30 juin 2017, 471 patients ont ete inclus. Le Tableau 1 resume leurs caracteristiques. Les patients sont majoritairement des hommes (69,6 %), âges de moins de 75 ans (84,4 %) atteints d’un CBNPC non epidermoide (67,9 %). Les fumeurs actifs ou sevres representent 95,4 % des cancers epidermoides et 89,4 % des cancers non epidermoides. A l’initiation du nivolumab, 83,4 % des patients ont un statut ECOG ≤ 1, 91,7 % ont un CBNPC de stade IV, 4,2 % presentent une mutation EGFR et 1,1 % un rearrangement ALK. Pres de 24 % des patients de stade IV presentent des metastases cerebrales, majoritairement asymptomatiques (83,8 %). Le nivolumab a ete administre en 2e et en 3e ligne pour respectivement 75,2 % et 16,8 % des patients. L’expression de PD-L1, evaluee par immunohistochimie chez 17,8 % des patients, a ete retrouvee chez 0 % des cancers epidermoides testes (n = 5) et 64,8 % des cancers non epidermoides testes (n = 54) avec une mediane a 35 % de cellules tumorales marquees [1–100]. A l’inclusion, la qualite de vie des patients, mesuree par l’echelle EQ-5D, etait sans difference selon le type histologique. Conclusion L’analyse preliminaire d’EVIDENS apporte une description precise de la population traitee en conditions de vie reelle par nivolumab pour un CBNPC avance en France. Les prochaines analyses permettront d’evaluer l’efficacite et la tolerance de ce traitement, ainsi que l’evolution de la qualite de vie des patients.

Background The EVIDENS study aims to describe clinical characteristics and health-related quality of life (HRQoL) of lung cancer patients treated with nivolumab in real-life in France and to assess its effectiveness and safety. Methods EVIDENS is an observational, multicenter, longitudinal cohort study of adult lung cancer patients treated with nivolumab. Survival was assessed using the Kaplan-Meier method and health-related quality of life (HRQoL) was assessed using EQ-5D-3L questionnaire. Results A total of 1,462 lung cancer patients were enrolled in the study from Oct 2016 to Nov 2017 in 146 French centers. Previous reports with a 8-month minimum follow-up showed that baseline patient and tumor characteristics from EVIDENS were representative of a standard advanced NSCLC population and that nivolumab was mostly administered as a 2nd line regimen. Median PFS and median OS was 2.8 months (95% CI: 2.6-3.0) and 10 months (95% CI: 9.2-11.0), respectively. Adverse events occurred in 440 patients (31.6%), including 98 patients (7.0%) with grade 3-4 events. Concerning HRQoL, mean change of visual analog score from baseline was statistically significant at 9 and 12 months and minimal important difference was achieved at 12 months for the squamous population. The analysis presented during the congress will include updated effectiveness, safety and HRQoL data as well as subgroups of interest (e.g. brain metastasis, age, prior radiotherapy) with a 17-month minimum follow-up. Conclusions TTo date, EVIDENS is the largest prospective observational study of nivolumab in lung cancer patients confirming effectiveness and safety in the real world setting. This updated analysis provides new insights on the experience of nivolumab over a period of longer follow-up and, for the first time, in clinically important subgroups of interest. Clinical trial identification NCT03382496. Legal entity responsible for the study Bristol-Myers Squibb France. Funding Bristol-Myers Squibb France. Disclosure A. Dixmier: Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: Novartis; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: Lilly. D. Debieuvre: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): GSK; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Mundipharma. J.B. Auliac: Advisory / Consultancy, Non-remunerated activity/ies: Bristol-Myers Squibb; Advisory / Consultancy: Roche. N. Benoit: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca. D. Moro-Sibilot: Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy: Takeda. C. Audigier-Valette: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (institution), Advisory / Consultancy: Roche. B. Asselain: Advisory / Consultancy: Bristol-Myers Squibb. P. Lamoureux: Full / Part-time employment: Bristol-Myers Squibb. F. Cotte: Full / Part-time employment: Bristol-Myers Squibb. V. Allan: Full / Part-time employment: Bristol-Myers Squibb. M. Daumont: Full / Part-time employment: Bristol-Myers Squibb. N. Ozan: Full / Part-time employment: Bristol-Myers Squibb. C. Calvet: Full / Part-time employment: Bristol-Myers Squibb. M. Perol: Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Takeda; Advisory / Consultancy: Clovis. All other authors have declared no conflicts of interest.

Resume Introduction Le College des pneumologues des hopitaux generaux (CPHG) propose de mener, dix ans apres l’etude KBP-2000-CPHG, une nouvelle etude epidemiologique observationnelle sur le cancer bronchopulmonaire (CBP) primitif. Patients et methodes Cette etude prospective porte sur tous les nouveaux cas de CBP primitif diagnostiques histologiquement ou cytologiquement entre le 1 er janvier et le 31 decembre 2010, et suivis dans un service de pneumologie d’un des centres hospitaliers generaux (CHG) participants. Son objectif principal est d’estimer la mortalite a cinq ans de ces patients et d’en rechercher les facteurs de risque. Ses objectifs secondaires sont de decrire les caracteristiques de cette population de patients, les modalites de leur prise en charge et d’estimer les taux de survie a un, quatre et cinq ans. Ces donnees seront ensuite comparees a celles obtenues lors de l’etude KBP-2000-CPHG. Le score pronostique a quatre ans developpe lors de l’etude KBP-2000-CPHG sera egalement teste dans cette etude. Les donnees sont recueillies au moyen d’un questionnaire standardise avec controle de l’exhaustivite. Resultats attendus Cent huit centres investigateurs ont accepte de participer a l’etude. Quatre mille a 5000 nouveaux cas de CBP primitif devraient etre collectes et analyses. Conclusion Cette etude permettra de decrire les caracteristiques des patients presentant en 2010 un CBP primitif suivis dans les CHG participant a l’etude, ainsi que leur prise en charge diagnostique et therapeutique. Elle va egalement permettre d’evaluer les changements survenus en dix ans.

Summary Purpose To evaluate the efficacy and safety of gemcitabine and carboplatin in the treatment of previously untreated patients with advanced non-small cell lung cancer (NSCLC). Methods A randomized phase II study was conducted by the Groupe Francais de Pneumo-Cancerologie (GFPC) in 15 centers. The patients were randomized in either arm A (GC): gemcitabine 1250 mg/m 2 on days 1 and 8 + carboplatin AUC 6 mg/(mL min) on day 1; or in arm B (VP): vinorelbine 30 mg/m 2 weekly + cisplatin 80 mg/m 2 on day 1. Treatment cycles were repeated every 3 weeks. Results A total of 100 patients were randomized with stage IV or stage III NSCLC with malignant pleural effusion: 51 patients in arm A and 49 patients in arm B. A total of 190 cycles were administered in the GC arm and 172 cycles in the VP arm, with a median of four cycles per patient in each arm. The dose intensity was 84.9% for gemcitabine, 99.8% for carboplatin, 97.7% for cisplatin and 67.7% for vinorelbine. The objective response rates were 19.6% (95% CI, 9.8–33.1) for GC and 29.2% (95% CI, 17.0–44.1) for VP in an ITT analysis. The response duration was 169 days in arm A and 226 days in arm B. The TTP was similar with 140 days (GC) and 148 days (VP), respectively. Overall survival rates were 334 days in the GC combination and 304 days in the VP combination. Overall, the treatment was safe and toxicities observed were different in each arm: neutropenia was the most common toxicity in the VP treatment, whereas thrombocytopenia was more frequent in the GC combination. Anemia was similar in both arms. Non-haematologic toxicity was mild. One toxic death in arm A and three toxic deaths in arm B were observed. Conclusion In terms of response rate, the gemcitabine–carboplatin combination was not efficient enough to allow further phase III study. Survival data are in the same range as the standard arm. This chemotherapy is feasible and may represent an alternative to a standard cisplatin-based regimen, allowing treatment in an outpatient setting.

As the incidence of primary lung cancer in women seems to be increasing in parallel with that of smoking, we conducted an exhaustive epidemiological study in 137 hospitals in 2000. We identified 904 women with proven primary lung cancer (mean age 63.9 years), many of whom have never smoked (32.3%), particularly in cases of adenocarcinoma (43.4%). Small cell cancer accounted for 16.1% of cases. Adenocarcinomas were the most frequent (45.3%) of the non-small cell lung cancer (NSCLC), followed by squamous cell (23.4%), large cell (11.6%) and bronchoalveolar (1.9%) carcinomas. About one third (32.2%) of NSCLC were stage III and 48.1% were stage IV. Over half of all adenocarcinomas were stage IV. According to multivariate analysis, adenocarcinoma is related to less smoking and younger age. In conclusion, many women affected by lung cancer have never smoked. Adenocarcinoma appears to be the most frequent form and more often at a metastatic stage.

Background: No standard treatment is defined for elderly patients with small cell lung cancer (SCLC). Carboplatin and etoposide are highly active agents against SCLC. In this study, we evaluated the activity and toxicity of a combination of these two agents. Patients and methods: Thirty-four untreated patients with limited or extensive SCLC and median age of 73.9 years entered the study. Chemotherapy consisted of carboplatin i.v. on day 1 (AUC 5 using Calvert's formula) and etoposide 100 mg/m 2 given orally on days 1–5, every 4 weeks, and thoracic irradiation was given to limited disease patients after chemotherapy. Results: The overall response rates was 59% (95% CI: 43–76). The median survival for all patients was 37 weeks (range 3–76 weeks). The toxicity was mainly haematological with grade 3–4 neutropenia in 59% of courses, febrile neutropenia in 15% of courses, and toxic death in 9% of patients. Conclusion : The results of this regimen are disappointing with worse response and survival, and more haematological toxicity than expected and previously reported, despite the use of Calvert's formula. Possible explanations are the use of etoposide per os rather than i.v., the frequent comorbidities of older patients and the inclusion of patients with poor prognosis factors.

Resume Introduction La neuroborreliose est un diagnostic parfois difficile, reposant sur un faisceau d’arguments epidemiologiques, cliniques et biologiques. Observations Nous rapportons deux observations de paralysie recurrentielle unilaterale avec une serologie de Lyme positive et une evolution favorable apres traitement antibiotique. Une meningite lymphocytaire avec synthese intrathecale d’immunoglobulines specifiques s’y associe dans un cas. Conclusion La paralysie recurrentielle est une manifestation originale de neuroborreliose. La serologie de Lyme reste un outil de choix devant des troubles neurologiques inexpliques vue la tournure tres atypique que peut prendre cette affection.

Resume Objectif de l'etude Evaluer prospectivement l'efficacite et la faisabilite d'une chimioradiotherapie en split course chez des patients atteints d'un carcinome bronchique non a petites cellules non metastatique. Materiel et methodes De mars 1996 a decembre 1997, 28 patients ont participe a une etude de phase II de chimioradiotherapie. La chimiotherapie associait de la vinorelbine (20 mg/m 2 /j a j1 et j5), du cisplatine (20 mg/m 2 /j de j1 a J5) et du 5-fluorouracile (350 mg/m 2 /j en perfusion continue de j1 a j5). La radiotherapie delivrait 2,5 Gy/j de j1 a j5. Les cycles etaient repetes toutes les quatre semaines. Une premiere evaluation de la reponse etait programmee apres quatre cycles (50 Cy). Un cinquieme cycle etait propose aux patients en cas de reponse complete ou partielle. Resultats Seuls les dossiers de 27 des 28 patients traites ont ete analyses. Un patient avait des metastases a distance au moment du diagnostic. La toxicite aigue a ete surtout hematologique, avec sept episodes d'aplasie febrile (26 %). Les 27 patients ont recu entre un et cinq cycles (mediane: quatre cycles). Quatre patients ont recu moins de trois cycles et leurs dossiers n'ont pas ete evalues pour la reponse. Sur les 23 patients evalues, 12 reponses (52 %) ont ete observees, dont trois completes (13 %) et neuf partielles (39 %). La duree mediane de la surveillance etait de 14 mois et la survie mediane de 13,5 mois. Les taux de survie a un an et deux ans etaient respectivement de 63 % et 14 %. Le taux de controle local etait de 11 % et 44 % des patients ont eu une evolution metastatique. Conclusion Les resultats tres preliminaires obtenus dans cette etude de phase II etaient globalement inferieurs a ceux obtenus avec les chimioradiotherapies classiques, avec une toxicite hematologique non negligeable. Ce type d'association ne peut etre recommande.

resume Parce que la scintigraphie est peu specifique et trop sensible, deux marqueurs biochimiques du remodelage osseux, la desoxypyridinoline (DPYR) et le telopeptide C terminal du collagene de type I (CTX) ont ete evalues au sein d'une population de patients avec un cancer bronchique dans le but de diagnostiquer, de facon precoce, les metastases osseuses.La population sans metastase montre une augmentation significative versus la population normale pour l'excretion urinaire de la DPYR et le CTX. Au sein de la population avec metastase osseuse, l'augmentation des concentrations excretees de DPYR et CTX est plus importante que celle de la population sans metastase ; cette augmentation est significative versus la population normale avec p p −1 de creatinine et pour le CTX = 429 μg mmol −1 de creatinine. Ces marqueurs doivent etre utilises avec prudence chez les femmes menopausees.

This report describes a case of paraneoplastic neurological syndrome associating a subacute sensory neuronopathy and an intestinal pseudo-obstruction in a 64-year old man with a small cell lung cancer. Various paraneoplastic neurological syndromes have been described in association with small cell lung cancer. In our patient anti-Hu antibodies were identified by indirect immunohistochemistry and western-blot analysis. This antibody constitutes an informative tool in assessing the paraneoplastic origin of neurologic symptoms when the etiological inquiry is negative. Its positivity is important in promoting the search for an underlying malignancy and should lead to repeat investigations if the first investigations are normal.

The College of General Hospital Respiratory Physicians (CPHG) is following up the KBP-2000-CPHG study, performed ten years ago, with a new observational epidemiological study of primary lung cancer.The study includes all new cases of primary lung cancer diagnosed on histology or cytology between 1 January and 31 December 2010 and managed by one of the general hospital pneumology departments participating in the study. The primary objective is to estimate five-year mortality and to analyze risk factors. Secondary objectives are to describe the characteristics of this patient population and their management, and to estimate one, four and five-year survival rates. These data will be compared to those of the KBP-2000-CPHG study. The four-year prognosis score developed in 2000 will also be assessed in the new study. Data are collected by standardized questionnaire with exhaustiveness control.One hundred and eight investigating centers have agreed to participate; 4000 to 5000 new cases of primary lung cancer should be collected and analyzed.The study will describe the characteristics of patients presenting with primary lung cancer in the participating pneumology departments during the year 2010, and their diagnostic and therapeutic management, and assess changes over the last ten years.

Neuroborreliosis can be a difficult diagnosis which requires epidemiologic, clinical and biologic arguments.We report two patients who presented with a recurrent laryngeal nerve palsy with positive Lyme serology and favorable outcome after antibiotic therapy. In one case, a lymphocytic meningitis with intrathecal production of specific antibodies was evidenced.Recurrent laryngeal nerve palsy is an uncommon manifestation of neuroborreliosis. Lyme serology is an important tool when neurologic disorder occurs because of an atypical course of Lyme disease.

International audience; CONTEXT: The objective of this study was to evaluate the feasibility and activity of weekly docetaxel monotherapy in frail elderly patients with advanced-stage non-small-cell lung cancer, selected on the basis of their precise age, general condition, and number of comorbid disorders (Charlson score). METHODS: Analysis of the response rate, toxicity, quality of life, median survival and 1-year survival rates after 1-3 six-week cycles of docetaxel 30mg/m(2) weekly. RESULTS: Fifty patients were enrolled and 42 were assessable. Five patients (10%, [3.7-22.6]) had objective responses, 14 (28%, [16.9-41.6]) had stable disease, and 23 (46%, [32.6-52.8]) progressed. The main grade 3-4 toxicity was fatigue (30%). Quality of life remained stable during treatment. The median survival time was 4.3 months, and the 1-year survival rate was 21.8%. CONCLUSION: In frail elderly patients selected on the basis of their age, general condition and comorbidity, weekly docetaxel monotherapy has acceptable toxicity and does not negatively affect quality of life. In contrast, it has only moderate activity.

Background: Brain metastases (BM) considerably worsen the prognosis of non-small-cell lung cancer (NSCLC) patients. The usefulness and choice of chemotherapy remain uncertain in this indication since these patients are excluded from most clinical trials. We conducted a phase II study to determine the efficacy and tolerability of up-front chemotherapy with association of temozolomide and cisplatin in NSCLC patients with BM. Patients and methods: Fifty NSCLC patients with BM received temozolomide (200 mg/m2/day for 5 days every 28 days) and cisplatin (75 mg/m2 at day 1 of each cycle), up to six cycles, followed by whole brain radiotherapy (WBRT). An evaluation was carried out every two cycles and after WBRT. WBRT was performed earlier in case of progressive disease at any time or stable disease after cycle 4. Results: Eight objective responses were achieved (16%). Overall median survival was 5 months. Median time to progression was 2.3 months. Ten patients (20%) presented a grade 3/4 neutropenia and 11 patients (22%) presented a grade 3/4 thrombopenia. Conclusion: This study demonstrates a lack of efficacy of up-front chemotherapy with association of temozolomide and cisplatin in these patients. Nevertheless, it supports the feasibility of chemotherapy before brain radiotherapy in NSCLC patients with BM.

To evaluate the efficacy and safety of gemcitabine and carboplatin in the treatment of previously untreated patients with advanced non-small cell lung cancer (NSCLC).A randomized phase II study was conducted by the Groupe Français de Pneumo-Cancérologie (GFPC) in 15 centers. The patients were randomized in either arm A (GC): gemcitabine 1250 mg/m2 on days 1 and 8+carboplatin AUC 6 mg/(mLmin) on day 1; or in arm B (VP): vinorelbine 30 mg/m2 weekly+cisplatin 80 mg/m2 on day 1. Treatment cycles were repeated every 3 weeks.A total of 100 patients were randomized with stage IV or stage III NSCLC with malignant pleural effusion: 51 patients in arm A and 49 patients in arm B. A total of 190 cycles were administered in the GC arm and 172 cycles in the VP arm, with a median of four cycles per patient in each arm. The dose intensity was 84.9% for gemcitabine, 99.8% for carboplatin, 97.7% for cisplatin and 67.7% for vinorelbine. The objective response rates were 19.6% (95% CI, 9.8-33.1) for GC and 29.2% (95% CI, 17.0-44.1) for VP in an ITT analysis. The response duration was 169 days in arm A and 226 days in arm B. The TTP was similar with 140 days (GC) and 148 days (VP), respectively. Overall survival rates were 334 days in the GC combination and 304 days in the VP combination. Overall, the treatment was safe and toxicities observed were different in each arm: neutropenia was the most common toxicity in the VP treatment, whereas thrombocytopenia was more frequent in the GC combination. Anemia was similar in both arms. Non-haematologic toxicity was mild. One toxic death in arm A and three toxic deaths in arm B were observed.In terms of response rate, the gemcitabine-carboplatin combination was not efficient enough to allow further phase III study. Survival data are in the same range as the standard arm. This chemotherapy is feasible and may represent an alternative to a standard cisplatin-based regimen, allowing treatment in an outpatient setting.

We initiated at Hospital de Mulhouse a prospective phase II study to assess a split-course concurrent radiochemotherapy in locally advanced non-small cell lung cancer.From March 1996 to December 1997, 28 patients were included in our study. All patients had a stage III cancer. The chemotherapy scheduled included vinorelbine (20 mg/m2/d, d1 and d5), cisplatin (20 mg/m2/d, from d1 to d5), and 5-Fluorouracil (350 mg/m2/d, from d1 to d5 by continuous infusion). The planned irradiation dose was 12.5 Gy per week with one daily fraction of 2.5 Gy from d1 to d5. Cycles were repeated every four weeks, for four cycles (50 Gy). Patients with a partial or complete response were proposed a fifth cycle.Of the 28 patients of the study, only 27 were analysed; one patient had a metastatic disease at diagnosis. Major hematologic toxicity occurred in 26% of the patients. One to five cycles of chemoradiotherapy were administrated per patient (median: four). Four patients had received fewer than three cycles and their responses were not assessable. Of the 23 patients assessed, 12 responses (52%) were observed, three CR (13%) and nine PR (39%). Median follow-up was 14 months, and median survival 13.5 months. One- and two-year survival rates were respectively 63% and 14%. Local control rates was 11%, and 44% of the patients had a metastatic evolution.Very preliminary results of this phase II study are disappointing, and quite inferior to the published results using chemoradiotherapy with conventional or hyperfractionated radiotherapy. Hematologic toxicity is restrictive. This type of chemoradiotherapy cannot be recommended.

We report the case of a patient, 62-year-old, with a non small cell lung cancer treated by right pneumonectomy followed by chemo and radiotherapy. After surgery appeared a refractory hypoxemia increasing with supine position. Cardiac catheterism showed a right left shunt by reopening of the "foramen ovale". We have performed foramen's occlusion by endovascular method with prothetic material with good result until the death, 14 months later, by neoplasic evolution.

Type 1 neurofibromatosis considerably increases the risk of cancer development, particularly neurosarcoma. We report a case in a patient with chemosensitive metastatic neurosarcoma.A young female patient with familial type 1 neurofibromatosis developed pleural metastasis of a neurosarcoma located on the arm. This tumor was initially highly sensitive to chemotherapy, but relapse occurred.Follow-up in the order members of the family was particularly difficult to organize. One sister developed cerebral astrocytoma. Neurosarcomas develop earlier in patients with type 1 neurofibromatosis, worsening prognosis. We suggest a prospective and structured registration of such cases using a network of clinicians and pathologists in order to improve management schemes.

This report describes a case of paraneoplastic neurological syndrome associating a subacute sensory neuronopathy and an intestinal pseudo-obstruction in a 64-year old man with a small cell lung cancer. Various paraneoplastic neurological syndromes have been described in association with small cell lung cancer. In our patient anti-Hu antibodies were identified by indirect immunohistochemistry and western-blot analysis. This antibody constitutes an informative tool in assessing the paraneoplastic origin of neurologic symptoms when the etiological inquiry is negative. Its positivity is important in promoting the search for an underlying malignancy and should lead to repeat investigations if the first investigations are normal.

Bronchogenic carcinoma is the most frequent carcinoma of men and affect more often old patients. Medical oncologists and pneumologists don't treat or treat with less intensive therapies patients older than 70 or 75 years compared with younger patients. That behaviour is not based on scientific criterias. The majority of the published studies are in fact retrospective with a lot of biases (especially selection of patients). It doesn't seem that nephrotoxicity is greater in older patients with cisplatinum but the neurological, digestive and medullary toxicities are more important in older than in younger patients.

We report a case of a 31 year old woman with recurrent hemothorax at the beginning of mens. Pleural biopsy confirmed the diagnosis of pleural endometriosis. Medical treatment with a Gn-RH analogue failed to cure and we realised surgical pleurodesis.

8163 Background. Thirty percent of lung cancer patients (pts) are 70 or older at diagnosis. However their representation in clinical trials is by far below and their management mostly unknown.We present here a survey about the management and determinants of survival of elderly lung cancer pts in France. Methods. Age categories (AC)(70–74, 75–80, 81–84, 85 and older), sex, social status, smoking habits, performance status (PS), comorbidities, histology, stage and treatment were studied. Results. From sept 02 to oct 03, 1540 pts were included by 77 centers. Data are available for 1000 pts. Median age was 76 (70–96). 810 were males (81%). 77% of males were married, 14% widowed (respectively 40% and 46.3% of females, p =2 in 44.8%. There was a trend towards a better PS in females (p = .056) and a significantly worst with increas...