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Background Immunotherapy using inhibitors targeting immune checkpoint programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) is currently the standard of care in patients with advanced non-small-cell lung cancer (NSCLC). Materials and methods We carried out a nationwide cohort retrospective study of consecutive patients with advanced, refractory NSCLC who received nivolumab as second to later lines of treatment as part of the expanded access program. Key objectives were to assess the efficacy and safety of nivolumab and the efficacy of first post-nivolumab treatment. Results Nine hundred and two patients were enrolled: 317 (35%) with squamous cell carcinoma and 585 (65%) with non-squamous cell carcinoma. Median age was 64 years; there were 630 (70%) men, 795 (88%) smokers, 723 (81%) patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0/1, 197 (22%) patients with brain metastases, and 212 (27%) with liver metastases. Best response was partial response for 16.2% and stable disease (SD) for 30.5%. Progression-free survival and overall survival (OS) rates at 2, 3, and 5 years were 8% and 25%, 6% and 16%, and 4% and 10%, respectively. At multivariate analysis, ECOG PS ≥2 [hazard ratio (HR) = 2.13, 95% confidence interval (95% CI) 1.78-2.55, P < 0.001], squamous histology (HR = 1.17, 95% CI 1.01-1.36, P = 0.04), and presence of central nervous system metastases (HR = 1.29, 95% CI 1.08-1.54, P = 0.005) were significantly associated with lower OS. Four hundred and ninety-two patients received at least one treatment after discontinuation of nivolumab, consisting of systemic therapies in 450 (91%). Radiation therapy was delivered to 118 (24%) patients. Conclusion The CLINIVO cohort represents the largest real-world evidence cohort with the use of immune checkpoint inhibitor in advanced, metastatic NSCLC after failure of first-line chemotherapy, with long-term follow-up and analysis of subsequent therapies. Our data confirm the efficacy of nivolumab in a cohort larger than that reported in landmark clinical trials and identify prognostic factors, which reinforces the need for accurate selection of patients for treatment with immune checkpoint inhibitors. Our data indicate that oligoprogression is frequent after nivolumab exposure and provide a unique insight into the long-term survival., Highlights • CLINIVO is the largest real-world evidence cohort with second-line nivolumab. • Progression-free survival and OS rates at 5 years were 4% and 10%, respectively. • Oligoprogression after nivolumab is frequent, with eligibility to radiotherapy.

Background BRAF mutations occurring in 1%–5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSe vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. Patients and methods Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). Results Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%–54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8–6.8), and OS was 10 months (95% CI 6.8–15.7). The vemurafenib safety profile was consistent with previous publications. Conclusion Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. Trial registration ClinicalTrials.gov identifier: NCT02304809.

Background Adjuvant treatment in resected stage I non-small-cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/β. We explored the feasibility and efficacy of adjuvant pazopanib in this population. Patients and methods In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/day (P800) for 6 months with a two-step Fleming design. The primary endpoint was compliance (percentage of patients receiving ≥3 months pazopanib). From the interim analysis after 64 patients were included, the IDMC recommended reducing to pazopanib 400 mg/day (P400) due to insufficient compliance, with a one-step Fleming. Although unplanned, survival data were analyzed. Results A total of 71 patients were enrolled in each arm; 61% were male, 91% were smokers, median age was 60 years, 80% had pathological stage IA, and 16% had squamous cell carcinoma. Pazopanib compliance was 38% [95% confidence interval (CI) 23–55] with P800, increasing to 69% (95% CI 50–84; P = 0.027) with P400. Two patients had grade 4 toxicities with P800. The most common grade 3 toxicities were increased transaminases (16%), hypertension (13%), and diarrhea (9%) with P800, and gastrointestinal disorders (16%; 6% diarrhea) and hypertension (6%) with P400. Median follow-up was 47 months. Three-year recurrence-free survival was 76% (95% CI 65%–86%) with pazopanib and 83% (95% CI 74%–92%) with placebo [hazard ratio = 1.3 (95% CI 0.6–2.7), P = 0.53]. Five-year overall survival was 83% (95% CI 72–94) with pazopanib and 94% [95% CI 88–100] with placebo [hazard ratio = 1.8 (95% CI 0.6–5.5), P = 0.26]. Conclusions In resected stage I NSCLC patients adjuvant 400 mg/day pazopanib but not 800 mg/day was feasible, although possibly infra-therapeutic and failed to improve relapse-free survival.

Background In 2013, the French National Cancer Institute initiated the AcSe program to provide patients with secure access to targeted therapies outside of their marketed approvals. Efficacy and safety was then assessed using a two-stage Simon phase II trial design. When the study design was designed, crizotinib was approved only as monotherapy for adults with anaplastic lymphoma kinase plus non-small-cell lung cancers (NSCLC). Patients and methods Advanced NSCLC patients with c-MET ≥6 copies, c-MET-mutated, or ROS-1-translocated tumours were enrolled in one of the three cohorts. Patients were treated with crizotinib 250 mg twice daily. Efficacy was assessed using the objective response rate (ORR) after two cycles of crizotinib as primary outcome. Secondary outcomes included disease control rate at four cycles, best ORR, progression-free survival, overall survival, and drug tolerance. Results From August 2013 to March 2018, 5606 patients had their tumour tested for crizotinib targeted molecular alterations: 252 patients had c-MET ≥6 copies, 74 c-MET-mutation, and 78 ROS-1-translocated tumour. Finally, 25 patients in the c-MET ≥6 copies cohort, 28 in the c-MET-mutation cohort, and 37 in the ROS-1-translocation cohort were treated in the phase II trial. The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the mutated, and 47.2% in the ROS-1 cohort. The best ORR during treatment was 32% in the c-MET-≥6 copies cohort, 36% in the c-MET-mutated, and 69.4% in the ROS-1-translocation cohort. Safety data were consistent with that previously reported. Conclusions Crizotinib activity in patients with ROS1-translocated tumours was confirmed. In the c-MET-mutation and c-MET ≥6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication. The continued targeting of c-MET with innovative therapies appears justified. Clinical trial number NCT02034981.

Introduction Le profilage moleculaire en routine chez les patients (pts) atteints d’un cancer bronchique non a petites cellules (CBNPC) avance est actuellement recommande ; la presence d’une mutation oncogenique ciblable est associee a une amelioration de la survie globale (SG). Methodes Les pts atteints de CBNPC ayant eu une analyse par les plateformes de genetique moleculaire entre avril 2012 et avril 2013 ont ete inclus dans la cohorte Biomarqueurs France [1] . Les donnees moleculaires (mutations de EGFR, rearrangements de ALK, mutations de HER2, KRAS, BRAF, PIK3CA) et cliniques ont ete collectees. Les resultats a long terme sont presentes avec un recul median de 5,6 ans. Resultats Au total, 18 645 analyses moleculaires de 17 632 pts (âge median 64,5 ans ; hommes 64,7 % ; fumeurs ou anciens fumeurs 81,2 % ; adenocarcinome 76,1 %) ont ete incluses. Le delai median entre la demande d’analyses et le rendu de resultats etait de 11 jours [IQ 25 %–75 % : 7–16]. Une alteration genetique a ete retrouvee dans 49,5 % des analyses : mutations de EGFR, HER2, KRAS, BRAF, PIK3CA ou rearrangement de ALK dans 11,0 ; 0,8 ; 28,8 ; 1,8 ; 2,3 et 4,8 % des cas, respectivement. La presence d’une alteration a eu un impact sur le traitement de 1re ligne pour 51,7 % des pts et etait associee a une amelioration significative de la survie sans progression de 1re ligne (9,2 [95 %CI : 8,6–9,9] vs 7,2 [95 %CI : 6,3–7,9] mois, p = 0,002) et de la SG (16,5 [95 %CI : 15,2–17,9] vs 12,0 [95 %CI : 10,4–13,5] mois, p Conclusion La frequence des alterations genetiques, le delai de rendu des resultats et le benefice clinique a long terme de la detection d’une alteration montrent l’interet du profilage genetique de routine au niveau national.

Background We raise the hypothesis that a STOP and GO strategy with induction by double immunotherapy Nivolumab + Ipilimumab combination during 6 months, followed by observation in patients with disease control (DC) at 6 months, would not be inferior to immunotherapy combination continuation until progression or unacceptable toxicity, in terms of progression-free survival, allowing lower toxicities cumulative rates, better quality of life and lower costs. Such strategy should not penalize overall survival, provided resuming immunotherapy at disease progression before second-line platinum-based chemotherapy. Trial design This is an open-label, randomized, phase III study in adult (≥18 years) patients, with stage IV non-small cell lung cancer, PD-L1 positive tumors, previously untreated for advanced disease. Subjects will first be locally assessed for PD-L1 expression, using 1% cut-off. Patients with enough tumor samples for central PD-L1 expression assessment, will be given first-line Nivolumab+Ipilumumab combination as followed: Nivolumab administered IV over 30 minutes at 3 mg/kg every 2 weeks combined with Ipilimumab administered IV over 30 minutes at 1 mg/kg every 6 weeks. Only patients with DC (objective response or stable disease), confirmed at 6 months, after a 1rst tumor evaluation at 3 months or beyond in case of pseudo-progression needing tumor reassessment, and without drug-related toxicity commanding treatment discontinuation will be randomized 1:1 either to continuation of Nivolumab+Ipilumumab combination until disease progression or unacceptable toxicity, or to clinical and radiological observation from week 24. Subjects receiving Nivolumab+Ipilimumab beyond investigator assessed progression must also continue tumor assessments until treatment discontinuation. Enrollment will end after approximately 868 subjects have been randomized (25/months). The primary endpoint of the study is Progression-Free Survival. Clinical trial identification NCT03469960. Legal entity responsible for the study IFCT (French Cooperative Thoracic Intergroup). Funding Bristol-Myers Squibb. Disclosure All authors have declared no conflicts of interest.

Introduction: Prison inmates are known to be more exposed to various lung cancer risk factors, and some studies have shown that lung cancer is the most common cancer in prisoners. However, no study has particularly focused on lung cancer features in this population. Method: Charts of patients with lung cancer hospitalized in one of the French secured hospital units between 1997 and 2012 were reviewed. Data from this cohort were then compared to those of two large observational studies conducted in 2000 and 2010 (KBP studies). Results: Thirty-two cases were included. All were men. The mean age was 52.2 ± 11.5 years, which was significantly lower than in the KBP-2000 (64.4 years) and KBP-2010 (65.5 years; both p < 0.0001) studies. The percentage of current smokers was much higher in prisoners (87.1 vs. 52.2 and 49.2%, respectively; both p < 0.001). Ninety percent of prisoners presented with at least one comorbidity. Lung cancer clinical presentation did not differ between prisoners and the reference populations. The median overall survival was 5.8 months (range 0-15.1) for all stages and 4.7 months (range 2.8-6.6) for stage IIIB/IV. Conclusion: Although our study suffers from limitations, prisoners seem to develop lung cancer at a younger age and their prognosis is poor.

Introduction Plusieurs recommandations proposent une surveillance reguliere clinique et scanographique thoracique apres chirurgie d’un CBNPC. En l’absence de donnees issues d’essais randomises publies, ces recommandations correspondent plutot a des avis d’experts. L’etude multicentrique IFCT-0302 a compare 2 programmes de surveillance apres exerese complete d’un CBNPC de stade clinique I, II et IIIA et T4 (plusieurs nodules dans le meme lobe) N0-2 (TNM 6e edition). Methodes Dans le groupe « minimal » (G1), la surveillance etait clinique et par radiographies thoraciques (RT). Dans le groupe « scanner » (G2), elle comportait le meme suivi clinico-radiographique mais egalement un scanner thoraco-abdominal et une fibroscopie bronchique (obligatoire uniquement en cas de tumeur nonadenocarcinomateuse). La surveillance etait semestrielle pendant 2 ans puis annuelle jusqu’a 5 ans. Des examens supplementaires n’etaient autorises qu’en cas de symptomes. Le critere de jugement principal etait la survie globale (SG). Resultats Entre janvier 2005 et novembre 2012, 1775 patients ont ete randomises (G1 : 888 ; G2 ; 887). Les caracteristiques des patients ne differaient pas entre les 2 groupes : hommes 76,3 %, âge median 63 ans (34–88), epidermoides ou grandes cellules 39,5 %, stades I 68,1 %, stades II 13,7 %, stades III 18,3 %, lobectomie ou bilobectomie 86,6 %, radiotherapie pre- et/ou postoperatoire 8,7 %, et chimiotherapie pre- et/ou postoperatoire 45 %. Le suivi median etait de 8,7 ans (IC95 % : 8,5–9). Il n’y avait pas de difference de SG (HR = 0,94 ; IC95 % : 0,81–1,08 ; p = 0,37). Les survies medianes et a 3 ans etaient respectivement de 8,2 ans (IC95 % : 7,4–9,6) et 77,3 % (IC95 % : 74,5 %–80,0 %), et 10,3 ans (IC95 % : 8,4–non-atteinte) et 76,1 % (IC95 % : 73,3 %–78,9 %), dans les groupes 1 et 2. Les taux de survie a 8 ans etaient respectivement de 51,7 % (IC95 % : 47,8 %–55,5 %) et 54,6 % (IC95 % : 50,9 %–58,3 %). Les survies sans recidive medianes et a 3 ans etaient respectivement non atteinte et 63,3 % dans le groupe 1, et de 4,9 ans et 60,2 % dans le groupe 2. Conclusion L’etude IFCT-0302 est la premiere large etude randomisee de surveillance des CBNPC operes. Les resultats montrent que le recours au scanner thoraco-abdominal systematique ne prolonge pas la survie apres une chirurgie de CBNPC. Cependant, un benefice de survie a long terme est possible chez les patients avec une surveillance par scanner thoraco-abdominal.

Introduction En 2011, un consensus international (Fearon) a propose de classer la cachexie cancereuse (CAX) en differents stades de severite croissante : pre–CAX (P-CAX), CAX et CAX refractaire (CAX-R). Si la definition de la CAX repose sur des criteres precis : perte de poids, diminution de la MM (sarcopenie) et anorexie, la P-CAX et la CAX-R sont moins bien definies. L’objectif de l’etude etait de determiner la frequence de CAX et de mieux identifier les stades de P-CAX et CAX-R. Methodes Notre etude transversale, prospective, multicentrique a inclus des patients CPNPC, quels que soient le stade et la ligne de traitement. La MM a ete evaluee par l’analyse des coupes en L3 du scanner. Les patients completaient les questionnaires EORTC QLQ-C30 (qualite de vie) et IPAQ (activite physique). Le critere principal etait la frequence de CAX. Resultats En 2016, 531 patients ont ete inclus en 3 mois par 52 centres francais et 4 belges. La MM a ete mesuree pour 312 patients. La population comportait 66,5 % d’hommes, âge median 66 ans, 79,9 % PS ECOG 1 g/L (45,7 %). Les % de patients dans les differents stades de CAX etaient : 33,8 % (P-CAX), 38,7 % (CAX) et 0,9 % (CAX-R) et etaient associes au nombre de sites metastatiques (p = 0,03) et a l’evolutivite du cancer (p Conclusion Il s’agit de la premiere etude qui, en incluant la mesure de la MM, a evalue les differents stades de CAX dans le CPNPC et a montre leur association avec les parametres fonctionnels de qualite de vie et d’activite physique. La relation entre les stades de CAX et la presence des anomalies moleculaires est interessante a explorer, de meme que la proportion elevee d’hyperglycemie (role de l’IGF et des corticoides ?).

Introduction Les mutations de K-Ras sont presentes dans environ 20 a 30 % des cancers bronchiques non a petites cellules (CBNPC). Elles sont oncogeniques mais peut-etre pas toutes addictives. Leur valeur pronostique et predictive n’est pas certaine. Des efforts recents de demembrement moleculaire suggerent qu’elles ne sont pas equivalentes en termes d’activation de voies de signalisation. L’etude « Biomarqueurs France » a inclus 18 000 CBNPC dont 4834 (27 %) mutes K-Ras. Le but de ce projet etait de demembrer les mutations de K-Ras afin d’en caracteriser les phenotypes, la valeur pronostique et la valeur predictive sur le traitement de premiere ligne. Methodes Les donnees cliniques (sexe, tabagisme, stade TNM, traitements 1re et 2e ligne), de biologie moleculaire (type de mutation, technique), survie sans progression (SSP), survie globale (SG) etaient disponibles pour 983 patients. Objectif principal : survie globale (SG), objectifs secondaires : survie sans progression (SSP) et facteurs predictifs de survie. Resultats Les patients etaient des hommes (67,1 %), fumeurs (96,4 %), âges de 62,1 ans (mediane, range 30–87,7), PS 0–2 (93,9 %), ayant un adenocarcinome (82,7 %), de stade III–IV (95 %). Les mutations les plus frequentes etaient les G12 C, les G12 V, puis les G12D ( Tableau 1 ). La frequence des G12 C etait plus elevee chez les fumeurs (42 vs 30 %), celle des G12 V identique (19 vs 20 %) et celle des G12D inferieure (13 vs 45 %) a celle des non-fumeurs, respectivement. L’analyse de la SSP en 1re ligne ne montrait pas de difference, de meme que l’analyse de la SG ( Tableau 1 ) pour les differentes mutations. En classant les mutations en deux groupes : transitions (n = 210) versus transversions (n = 716), la SSP (4,3 vs 5,0, p = 0,39) et la SG (7,4 vs 10,3, p = 0,46) n’etaient pas differentes. Conclusion Malgre l’analyse d’un grand nombre de patients mutes K-Ras, il n’a pu etre mis en evidence de difference de valeur pronostique ou predictive des types de mutations de K-Ras.

Introduction Subcutaneous implanted ports (SIP) are long-term devices often used in oncology practices because they have fewer infectious complications than others central venous catheters and because they preserve a better quality of life for patients, especially for sequential treatments. In literature, the incidence of infectious complications on SIP differed depending on patient's pathology, perfusions (parenteral nutrition), catheterization durations and other infectious events. Methods In order to meet the demand of lung specialist to decrease infections, an observational study was conducted to describe the infectious complication incidence and to identify the risk factors of catheter infections during two periods before and after a multimodal infection prevention program. All patients who had undergone SIP insertion, whatever the indication, during a stay in one of the three units of Pulmonology were included in the study. Two periods of surveillance were studied: (i) P1 of November 15 2012 to December 31, 2013; and (ii) P2 from September 1, 2014 to November 1, 2015. All patients were followed prospectively from the date of SIP insertion to the occurrence of the first infection, until the removal of SIP, until the death of the patient, or for a maximum of 6 months. The incidence of catheter infection is expressed as events per 1000 catheter days. Catheterization days were calculated from the start date of insertion to the end of the follow-up. During P1, parameters collected were demographic factors of patients, diabetes, patient dependence score, infectious disease history, indication and SIP placement, first or second SIP, immediate complications after catheter placement (hematoma), perfusions type (transfusion, chemotherapy, parenteral nutrition). During P2, the statistically significant factors of P1 were recorded. In univariate analysis Pearson's Chi2 test and the Z test were used. For multivariate analysis, a Cox model was used for the comparison of survival of CVC without an infection-related problem. Each factor related to infectious risk in univariate analysis and interactions was included in the model. Univariate and multivariate analyses were made using SPSS software. Results All patients have care both in hospital (in ambulatory care unit or hospitalized unit) and at home. During the first period, 61 SIP for 56 patients were included covering a total of 6,966 catheterization days. The incidence of infections was 2.87 per 1000 catheter days corresponding with 16 catheter-related bloodstream infections (CRBSIs) and 4 local SIP infections.17 SIP were removing because of infection. Staphylococcus epidermidis, Staphylococcus aureus and Enterobacter cloacae were the main microorganisms identified. Four early infections occurred within 7 days after inclusion. A multivariate analysis highlighted a significant effect of parenteral nutrition (OR = 4.94, P –hospital and home nurses formation with posters summarizing points main parts of infection catheter prevention and evaluation of knowledge on aseptic catheter protocols; –used of taurolidine lock prophylaxis for patient with parenteral nutrition; –observations and education of surgical staff on hand hygiene and aseptic technique. During the second period, 69 SIP for 60 patients were included covering a total of 9343 catheterization days. Incidence of infections was 0.71 per 1000 catheter days corresponding with 4 CRBSIs and 3 local SIP infections. No early infections were observed. A very important decrease of incidence of infections was observed between the two periods. Conclusion This result shows that the application of a prevention program with a multidisciplinary approach involving medical and chirurgical staff, nurses working in and out hospital to provide continuing education to all healthcare providers, is efficacy to decrease this infections.

Background Positron emission tomography with 2-[18]-fluoro-2-deoxy-D-glucose coupled to a dedicated CT scanner (FDG-PET-CT) is an accurate test for the diagnosis of malignancy of pulmonary nodules. We have assessed the diagnostic accuracy of this test at the Lyon Sud Hospital Centre (LSHC). Methods We examined retrospectively 93 patients with no past history of cancer who had had a FDG-PET-CT evaluation for the diagnosis of pulmonary nodules or mass lesions between the 1st January 2005 and the 30th June 2006 at the CHLS. The results of the PET scans were compared with the histological findings or follow-up imaging. Results The sensitivity was 97.85 (IC 95% Sc =[93.4; 100]), the specificity was 79.2% (IC95% Sc=[67.6; 90.7]), the positive predictive value was 81.5%, the negative predictive value was 97.4% and the accuracy was 88.2%. Conclusions In current practice these results support the validity of FDG-PET-CT at the LSHC for the diagnosis of malignancy of pulmonary nodules and mass lesions while giving nuclear medicine physicians the opportunity to improve their standards of practice.

Purpose The objective of this randomised phase II study was to evaluate the impact in terms of response and toxicities of induction or consolidation chemotherapy respectively before or after concurrent chemoradiotherapy in unresectable stage III non-small-cell lung cancer. Patients and methods In the induction arm, patients received induction chemotherapy with cisplatin (80 mg/m 2 ) and paclitaxel (200 mg/m 2 ) on days 1 and 29 followed by a concurrent chemoradiotherapy (66 Gy in 33 fractions, cisplatin 80 mg/m 2 days 1, 29 and 57, vinorelbine 15 mg/m 2 days 1, 8, 29, 36, 57 and 64). In consolidation arm, the same concurrent chemoradiotherapy began on day 1 followed by two cycles of cisplatin and paclitaxel. Results One hundred twenty seven patients were randomised. The intent to treat response rates in induction and consolidation arms were 58% and 56% respectively. Median survival was 19.6 months in induction arm and 16.3 months in consolidation arm and 4-year survival rates were 21% and 30% respectively. Haematologic and non-haematologic toxicities were similar in both arms, except grade 3/4 oesophagitis, more frequent in consolidation arm than in induction arm (17% versus 10%). Conclusion Cisplatin-based chemotherapy as induction or consolidation with concurrent chemoradiotherapy can be administrated safely. Response rates were similar in both arms with a trend in favour for consolidation arm for long-term survival.

Background: We conducted an economic analysis of a phase III clinical trial comparing sequential radiochemotherapy (RT-CT) with concurrent RT-CT in patients with locally advanced non-small-cell lung cancer. Patients and methods: The trial was a randomized multicenter study comparing three cycles of chemotherapy (arm A) followed by radiotherapy against an RT-CT combination (two cycles of platinum etoposide) followed by two cycles of platinum-vinorelbine (arm B). The economic analysis adopted the payer's perspective and only included direct costs. Costs (€, 1996–2003) were recorded until the cut-off date. A cost minimization analysis and a sensitivity analysis were carried out. Results: Data from 173 patients were used in the economic study. Protocol costs tended to be higher in arm B, while relapse costs were significantly higher in arm A. The total number of hospital days was higher in arm B. The average total cost per patient was €16 074 in arm A and €15 245 in arm B (P = 0.15). The cost minimization analysis favored arm B. This advantage persisted in the sensitivity analysis. Conclusions: Concurrent RT-CT was not the more costly strategy in this phase III trial, despite lengthier hospitalization for toxicity. Other studies of similar design are needed to confirm these results in future randomized trials.

Background This multicenter, randomized, phase III study compared the efficacy, including progression-free survival (PFS), and safety of gemcitabine–docetaxel (GD) combination versus cisplatin–vinorelbine (CV) in the treatment of advanced non-small-cell lung cancer (NSCLC). Patients and methods Chemonaive patients with stage IIIB or IV NSCLC were treated with GD (gemcitabine 1000 mg/m2 days 1 and 8 plus docetaxel 85 mg/m2 day 8, every 3 weeks for eight cycles) or CV (cisplatin 100 mg/m2 day 1 plus vinorelbine 30 mg/m2, days 1, 8, 15 and 22, every 4 weeks for six cycles). Results A total of 311 patients were enrolled (155 GD and 156 CV). Neither PFS nor overall survival differed significantly between the two arms (median PFS 4.2 and 4 months; median survival 11.1 and 9.6 months; 1-year survival 46% and 42%, for GD and CV, respectively). For the GD arm compared with the CV arm, the hazard ratio for PFS was 1.04 [95% confidence interval (CI) 0.83–1.32], and for overall survival, it was 0.90 (95% CI 0.70–1.16). Objective response rates did not differ significantly (31% for GD, 35.9% for CV). Myelosupression, emesis and frequency of febrile neutropenia were less pronounced on the GD arm, whereas fluid retention and pulmonary events were more pronounced. The CV arm experienced a higher number of serious adverse events and a lower compliance with the protocol. There was no quality of life (QoL) difference between arms. Median time to definite impairment of health-related QoL was 153 and 168 days in GD and CV arms, respectively. Conclusions There was no advantage in PFS with GD compared with CV; however, the CV regimen had higher rate of toxic events, mainly myelosuppression. The herein, non-platinum-containing regimen could be considered as a rational alternative to the cisplatin-based doublet.

Introduction Une maintenance (M) est la strategie habituellement realisee dans le traitement des cancers bronchiques non a petites cellules non epidermoides (CBNPCNE), apres une chimiotherapie d’induction (CT). Le benefice de la switch maintenance apparait plus grand pour les patients stables (MS) apres CT alors que la M de continuation est meilleure pour les patients en reponse objective (RO). Cet essai compare une strategie de M dependant de la reponse au doublet cisplatine (C) gemcitabine (G) : M par G pour les RO et M par pemetrexed (P) pour les MS, vs CP suivie de P, quelle que soit la reponse (RO et MS) apres la CT. Methodes Criteres d’inclusion : âge 18–70 ans, PS 0–1, CBNPCNE de stade IV en premiere ligne, naif de toute chimiotherapie, sans mutation EGFR ou translocation ALK connue, ineligible au bevacizumab. Randomisation 1 :1 entre CG 4 cycles puis M par G si RO et M par P si MS ou CP 4 cycles et M par P si MS ou RO. Objectif principal : survie globale (SG), objectifs secondaires : survie sans progression (SSP), RO, toxicites. Resultats Au total, 932 patients ont ete randomises entre 07/12 et 06/16 (CG : 467, CP : 465). Les caracteristiques des patients etaient homogenes entre les deux groupes. Au total, 255 patients (54,6 %) du groupe CG ont eu une M (G : 142, P : 113) et 274 (58,9 %) du groupe CP. Le nombre median de cycles de M etait de 5 pour CG et 4 pour P. La SG etait de 10,9 mois (m) pour CG vs 10,4 m pour CP ; HR ajuste 0,97 (IC95 % : 0,84–1,13, p = 0,72). La SSP etait de 5,0 m pour CG vs 4,7 m pour CP, HR ajuste 0,96 (IC95 % : 0,84–1,10). La RO apres la CT etait de 5,1 % pour CG vs 33,8 % pour CP. Les toxicites etaient celles attendues pendant la CT d’induction. Pendant la M, les toxicites hematologiques de grade ≥ 3 etaient de 28 % et 31 % des patients pour CG et CP respectivement : neutropenie febrile (2,4 % vs 1,1 %), anemie (9,4 % vs 11,7 %), thrombopenie (6,7 % vs 5,8 %). Aucune toxicite non hematologique de grade ≥ 3 n’etait constatee dans plus de 5 % des cas sauf l’asthenie (3,9 % CG vs 5,1 % CP). Conclusion L’adaptation de la strategie de maintenance a la reponse apres la CT d’induction n’apporte pas de benefice en termes de survie globale ou de survie sans progression.

Introduction Le nivolumab (N) est un traitement de reference du cancer bronchique non a petites cellules (CBNPC) des la 2 e ligne. En 2015, un programme d’autorisation temporaire d’utilisation du N a inclus de janvier a aout 2015 les CBNPC epidermoides (EPI) et de juin a aout 2015 les CBNPC non epidermoides (NON-EPI), des la 2 e ligne therapeutique. Cette cohorte offre l’opportunite d’evaluer l’efficacite et la tolerance du N et du traitement post-nivolumab (TPN) en condition de vie reelle. Methodes Au total, 902 patients presentant un CBNPC de stade IIIB/IV, ayant recu au moins une dose de nivolumab 3 mg/kg/2 semaines ont ete inclus dans l’etude. Les variables recueillies etaient : objectif principal : survie globale (SG), objectifs secondaires : survie sans progression (SSP) sous N et TPN, facteurs predictifs de survie, de reponse (RO) au N et TPN, toxicites maximales severes sous N (TMS). Resultats Les caracteristiques des patients etaient identiques selon les histologies (EPI et non EPI), a l’exception des non-fumeurs (6,9 vs 16,2 %) et des localisations cerebrales (12,6 vs 26,8 %). Le taux de TMS de grades ≥ 3 etait de 10,9 %. L’efficacite sous N etait : RO 19,0 % [16,2 ; 21,7], taux de controle 54,5 % [50,9 ; 58,0], SG 9,9 mois [9,1–11,3], SSP 2,0 mois [1,9–2,2]. On notait 2 facteurs pronostiques defavorables sous N : presence de metastases cerebrales : HR = 1,38 (IC95 % 1,15–1,67 ; p = 0,0007) et PS ≥ 2 : HR = 2,21 (IC95 % : 1,82–2,69 ; p Conclusion Les resultats d’efficacite et de tolerance du N dans ces indications sont comparables a ceux des essais cliniques. Le pronostic sous TPN est correle a la RO sous N.

Purpose: To determine if the timing of whole brain radiotherapy (WBRT) with respect to chemotherapy with cisplatin and vinorelbine would influence survival in patients with non-small-cell lung cancer (NSCLC) and concurrent brain metastasis. Patients and methods; One hundred seventy-six patients with brain metastasis from NSCLC were included in the study between July 1995 and October 1997. All patients received chemotherapy with cisplatin 100 mg/m 2 on day 1 and vinorelbine 30 mg/m 2 on days 1, 8, 15, 22. Cycles were repeated every four weeks. Evaluation of response was performed after two, four or six cycles. After two cycles, chemotherapy was administered to the responders to a maximum of six cycles. Patients were randomised to receive WBRT 30 Gy/10 fx/12 days and delayed corticosteroids, (arm A) for the intracranial nonresponders, or early on day 1 to 12 during the first cycle of chemotherapy (arm B). Results: One hundred seventy-one patients were eligible: eighty-six in arm A and eighty-five in arm B; none had received prior chemotherapy; seventy-six and seventy-three, respectively, were assessable for response. There was a 21% overall objective response rate (OR) (with I complete response and 17 partial responses) after two cycles of chemotherapy alone (arm A) and a 20% OR (with 17 partial responses) to chemotherapy and early WBRT (arm B). The intracranial OR was 27% and 33%, respectively (P = 0.12). The six months survival rate (46% and 40%) and the median survival duration (24 and 21 weeks, respectively) were not significantly different between the two arms (P = 0.83, log-rank test). The major toxicity was severe or life-threatening neutropenia (grade 4), which occurred in 35% of arm A patients and 36% of arm B patients. There were thirteen treatment-related deaths (six in arm A and seven in arm B). There was no difference between the arms for haematological and neuro-toxicities. Conclusions: These results confirm the efficacy of chemotherapy in brain metastases of NSCLC and suggest that the timing (early or delayed) of WBRT did not influence survival of NSCLC with brain metastasis treated with concurrent chemotherapy.

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.

Introduction Les patients âges sont les premiers concernes par les CBNPC et leur prise en charge rarement evaluee specifiquement. L’objectif de cette etude est de decrire en vraie vie en France les strategies therapeutiques de 1 re ligne incluant Bevacizumab chez des patients âges atteints de CBNPC. L’etude vise egalement a decrire leurs caracteristiques, survie sans progression, survie globale et qualite de vie ainsi que la tolerance au traitement. Methodes AVANTAGE est une cohorte prospective multicentrique, conduite chez des patients ≥ 65 ans, debutant une 1 re ligne de chimiotherapie associee a bevacizumab pour le traitement du CBNPC. Les donnees ont ete recueillies a l’inclusion (07/2013 a 12/2015), puis tous les 3 mois pendant 18 mois. Les raisons de non-prise en charge par bevacizumab ont ete recueillies pendant 6 mois. Resultats Deux cent soixante-dix-sept patients traites ont ete inclus dans 72 centres (50 % de CHG, 24 % de cliniques, 21 % de CHU et 5 % de CLCC). Un total de 248 patients ont ete retenus pour l’analyse : hommes (75 %), 65–69 ans (43 %) et ≥ 70 ans (57 %), index ECOG a 0 (42 %), score du questionnaire G8 > 14 (36 %), anciens fumeurs (64 %), stade IV (96 %), index de comorbidite de Charlson ajuste sur l’âge ≤ 3 (43 %). L’association sels de platine-pemetrexed-bevacizumab a ete prescrite chez 186 (75 %) patients (avec cisplatine dans 55 % des cas et carboplatine dans 45 % des cas). Les 62 (25 %) patients n’ayant pas beneficie de cette association ont recu d’autres agents (dont l’association carboplatine-paclitaxel-bevacizumab dans 69 % des cas). La posologie initiale de bevacizumab, instaure des le 1 er ou 2 e cycle de chimiotherapie chez 95 % des patients, etait de 7,5 (70 %) ou 15 (23 %) mg/kg/3 semaines. L’association sel de platine-pemetrexed-bevacizumab a ete prescrite chez 80 % des patients (85/106) de 65–69 ans et chez 71 % des patients (101/142) ≥ 70 ans. Cette association a ete plus frequente chez les patients de 65–69 ans (46 % vs 34 %), avec ECOG a 0 (45 % vs 33 %), score du questionnaire G8 > 14 (38 % vs 29 %), ou index de comorbidite de Charlson ajuste ≤ 3 (45 % vs 36 %). Les principales raisons de non-prescription de bevacizumab (chez les 108 patients repertories) etaient : âge du patient (18 %), localisation centrale de la tumeur (18 %), implication des gros vaisseaux (18 %), maladie arterielle (14 %) et ECOG ≥ 2 (10 %). Conclusion AVANTAGE montre que chez des patients âges eligibles a une chimiotherapie de 1 re ligne avec du bevacizumab, l’association la plus frequemment utilisee est celle d’un sel de platine et du pemetrexed (75 % des cas).

Background Despite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France. Methods A literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article. Results The multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55–74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given. Conclusions Individual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.

We report a case of acute respiratory distress syndrome (ARDS) in a 37-year-old man. Hypoxemia was refractory despite conventional treatment of ARDS, but the evolution was satisfactory after corticosteroid therapy. Biological data and the clinical evolution led us to the diagnosis of Churg-Strauss syndrome. This case incites us to reiterate that after having eliminating the usual causes of ARDS, the assumption of a systemic disease should be considered in order to begin the appropriate treatment as rapidly as possible.

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.

Aim: Activating BRAF V600E mutations in NSCLC are present in ≈1.5% of tumors, primarily adenocarcinomas, offering an opportunity to test targeted therapy for this disease. Methods: This single-arm, 2-stage design, Phase II study (NCT01336634) enrolled Stage IV BRAF V600E-mutant NSCLC patients (pts) determined by local laboratory testing. Pts received dabrafenib 150 mg twice daily. Primary endpoint was investigator-assessed overall response rate (ORR) per RECIST 1.1. Results: As of 30 April 2014, 84 pts (female 52%, median age 66 years [range 28–89], ECOG 0–1 86%, Asian 21%, never-smoker 37%, adenocarcinoma histology 96%) were enrolled from August 2011. Median duration on treatment was 4.3 months (range, 0.3–25.2) with 21 (25%) pts still on treatment. Six pts had not received any prior regimen for metastatic disease (first-line pts), 40 pts had one line and 38 pts had received ≥2 lines (range 2–9). ORR for 78 pts with ≥ one line of prior therapy (second-line plus pts) was 32% (n = 25, all partial responses [PRs]; 95% confidence interval [CI] 22–44%) and disease control rate (DCR) for >12 weeks was 56% (95% CI 45–68%), median duration of response (mDoR) was 11.8 months (95% CI 5.4–not reached) with 48% of responders progressed. Based on assessment by independent review committee (IRC), 64 second-line plus pts had measurable disease; ORR and DCR were 28% (n = 18; 95% CI 18–41%) and 52% (95% CI 39–64%) respectively, and mDoR has not been reached. Among the six first-line pts, three pts had PR, four pts had measurable disease based on IRC with three PRs. Most common (>25%) adverse events (AEs) were pyrexia (36%), asthenia (30%), hyperkeratosis (30%), decreased appetite (29%), nausea (27%), cough (26%), fatigue (26%) and skin papilloma (26%). Cutaneous squamous-cell carcinomas, including keratoacanthoma, were reported in 18%. Grade ≥3 AEs occurred in 45% with one event of grade 5 haemorrhage intracranial. Conclusions: Treatment of BRAF V600E mutated advanced NSCLC pts with dabrafenib demonstrated significant antitumor activity with durable objective responses and acceptable safety profile. Dabrafenib is the first drug of its class to show activity in a prospective trial of NSCLC with BRAF mutations. Disclosure: D. Planchard: has received personal fees for participating in advisory boards from AstraZeneca, BI, Lilly, Novartis, Pfizer, Roche and BMS; E. Quoix: has received honoraria for inclusion of patients into study from GSK; G.J. Riely: G.J.R.'s institution received a grant from GSK. G.J.R. received personal fees from Daiichi, Novartis and Abbott for consulting; F. Barlesi: has received a grant and personal fees from GSK; M.A. Socinski: received clinical trial support from GSK; C. Tucker: is an employee of GSK. C.T. owns stock in GSK; B. Ma: is an employee of GSK; B. Mookerjee: is an employee of GSK. B.M. owns stocks in Incyte Corporation and AstraZeneca; C.M. Curtis, Jr: is an employee of GSK. C.M.C.Jr owns stock in GSK; B.E. Johnson: has received personal fees from Roche/Genentech for being an expert witness; Roche/Genentech manufacture a competitor of dabrafenib (vemurafenib). B.E.J. has received personal fees from KEW Group for consultancy.All other authors have declared no conflicts of interest.

Despite surgery, resectable NSCLC (stage I, II, and IIIA N2) has a quite poor prognosis: about 50% of patients will die during the first 2 years by metastatic disease and only 36% are alive at 5 years after diagnosis. Postoperative radiotherapy is not effective in case of complete resection (PORT meta-analysis). The role of perioperative chemotherapy is still questionnable. Cambridge meta-analysis has shown a little benefit of cisplatin based postoperative chemotherapy. Several randomised trials are completed like Alpi Trial or ANITA or still in progress. Results would be available in 2 or 3 years. Several phase II trials of preoperative chemotherapy have demonstrated that preoperative chemotherapy is feasible, with high response rate, very few progression (mainly metastatic progression without local progression) and no increase of mortality and morbidity. Two small phase III trials have demonstrated that preoperative chemotherapy can dramatically increase survival compared with surgery alone, in case of N2 disease. The MIP trial of Depierre has studied two or four cycles of MIP regimen in perioperative setting in stage IB, II or IIIA, compared to surgery alone (TRT in case of N2 disease). After 3 years of survey there is a trend in favor of MIP in case of stage IB and II (23% increase of 3 years survival) but not in case of N2. The toxicity of MIP is a possible explanation of such poor results in N2 patients despite a high response rate (64%). Some other trials are in progress in the world. Surgery is also questionnable in case of resectable N2 disease. Several trials comparing chemo radiotherapy to chemo (+/- radiotherapy)+surgery are in progress in U.S. and Europe.

Objectifs Dans le cadre d’une initialisation d’un traitement antalgique par un morphinomimetique de palier III : modeliser l’usage d’une PCA IV en utilisant une morphine LI et un patch Durogesic*, choisi pour sa cinetique superposable a la voie IV et dont la latence de mise en route permet une titration prealable. Materiels et methodes Vingt patients presentant un cancer bronchopulmonaire et dont les douleurs ne sont pas controlees par un traitement antalgique de palier II et/ou une EVA > 5. A H + 0 pose d’un patch Durogesic* et administration de 10 mg de morphine LI, puis surveillance par EVA toutes les heures pendant 4 heures puis toutes les 4 heures pendant 24 heures. A chaque EVA > 3 : administration de 10 mg de morphine LI, pour obtenir une EVA Resultats EVA moyenne a: H + 0 = 6.2 (5 a 10) ; H + 2 = 2,98 ; H + 4 = 1,8 ; H + 12 = 0,95 ; H + 24 = 0,9. La consommation moyenne de morphine LI est de 21 mg pendant la titration. Aucun evenement indesirable n’a ete enregistre. Le patch Durogesic* assure une bonne stabilite du resultat de la titration. L’enquete de faisabilite montre: – aucune augmentation de la charge de travail ; – meilleure evaluation de douleur ; – controle plus rapide et plus efficace de la douleur ; – autonomisation accrue des personnels. Conclusions La titration horaire associee a un patch Durogesic* permet un controle aise, rapide et stable de la douleur aisee, sans augmenter la charge de travail du personnel soignant.