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Resume Introduction Le parcours de soins des patients atteints de cancers du poumon (CP) est complexe. L’objectif du Plan cancer 2014–2019 est la maitrise des delais de prise en charge. En 2016, un parcours diagnostic rapide ambulatoire du CP a ete mis en place dans le service de pneumologie. L’objectif de cette etude est d’evaluer sa faisabilite et son impact sur les delais de prise en charge. Methode Il s’agit d’une etude epidemiologique retrospective realisee au CHU de Tenon entre mai 2016 et mai 2017. Resultats Un diagnostic de CP a ete fait dans 60 % des cas (n = 118). Le delai median d’acces a la prise en charge (D1) (demande-consultation) etait de 4 jours (2–7). Le delai median d’acces a la proposition de traitement (D4) (histologie-RCP) etait de 4 jours (0–8). Le delai d’acces au premier traitement (D5) (RCP-traitement) etait de 10 jours (4–15) pour la chimiotherapie et de 27 jours (16–34) jours pour la chirurgie. Le delai global de pris en charge (D6) (imagerie-traitement) etait de 49 jours (34–70). Conclusion Les delais de prise en charge du CP etaient conformes aux recommandations internationales. L’infirmiere de coordination a occupe un role central organisationnel et dans l’accompagnement du patient.

International audience; Purpose: Maintenance chemotherapy is a reasonable choice for patients with metastatic non-small cell lung carcinoma (NSCLC) not progressing after induction therapy with a platinum-based doublet. Nevertheless, there have been no studies dedicated to elderly patients.Patients and methods: We conducted a randomised trial in patients aged 70-89 years, with advanced NSCLC (with neither EGFR mutation nor ALK rearrangement), who had not progressed after four cycles of monthly carboplatin and weekly paclitaxel in order to compare maintenance with either pemetrexed (500 mg/m2 d1, 22) in patients with non-squamous cell carcinoma or gemcitabine (1,150 mg/m2 d1, 8, 22) in squamous cell carcinoma to simple observation. The patients were required to have a performance status (PS) 0-2, mini-mental score >23, and creatinine clearance ≥45 mL/min. The primary end-point was overall survival (OS).Results: 632 patients were enrolled from May 2013 to October 2016. Of the 328 (52.3%) patients randomised after induction therapy, 166 patients were assigned to the observation arm, versus 162 to the switch maintenance arm, 119 of whom received pemetrexed and 43 gemcitabine. The median OS from randomisation was 14.1 months (95% confidence interval [CI]: 12.0-17.0) in the observation arm and 14 months (95% CI: 10.9-16.9) in the maintenance arm (p = 0.72). The median progression-free survival (PFS) from randomisation was 2.7 months (95% CI: 2.6-3.1) in the observation arm versus 5.7 months (95% CI: 4.8-7.1) in the maintenance arm (p < 0.001).Conclusion: Switch maintenance therapy significantly prolonged PFS but not OS and, thus, should not be proposed to elderly patients with advanced NSCLC.

Lung cancer is the leading cause of cancer related death among people living with HIV (PLHIV). Tobacco exposure is higher among PLHIV (38.5%) and mainly explains the increased risk of lung cancer. To reduce lung cancer mortality, two approaches need to be implemented: lung cancer screening with low-dose thoracic CT scan and smoking cessation. Low dose CT scan is feasible in PLHIV. The false positive rate is not higher than in the general population, except for cases with CD4

International audience; IntroductionPeople living with HIV (PLWHIV) are at a higher risk of cancer compared to the general population. With improved cancer treatments and the increased life expectancy of PLWHIV, the incidence of second cancers is also expected to increase.MethodsWe reviewed the cases of PLWHIV with cancer that have been presented to the CANCERVIH national multidisciplinary board since 2014. We included all cases with a history of cancer, and studied the incidence and types of second cancers.ResultsIn total, 719 cases were reviewed, out of which 94 (13%) had a history of at least one cancer. For the first primary cancers, 46 (49%) were AIDS-defining cancers (ADCs) and 48 (51%) were non-AIDS-defining cancers (NADCs). Kaposi sarcoma (33%) and NHL (15%) occurred most frequently as first cancers. Among the first cancers that were ADCs, 15% of the second cancers were NHL, 11% anal canal cancers, 9% bladder and 9% Hodgkin lymphomas. Among the first cancers that were NADCs, 38% of the second cancers were lung cancers, 8% bladder, 8% head and neck and 8% NHL.DiscussionWith the aging of PLWHIV, the incidence of second and subsequent cancers is expected to increase in this population. Immuno-virological control should be maintained. Increased surveillance, early prevention and screening programs should be offered to all PLWHIV, including those with an undetectable HIV viral load and/or immune restoration.; IntroductionLes personnes vivant avec le VIH (PVVIH) ont un risque plus élevé de cancer que la population générale. Avec l’amélioration des traitements carcinologiques et l’augmentation de l’espérance de vie des PVVIH, l’incidence des seconds cancers devrait augmenter.MéthodesNous avons examiné les dossiers des PVVIH atteintes d’un cancer qui ont été présentés en RCP nationale CANCERVIH depuis 2014. Nous avons inclus tous les cas avec antécédents de cancer, et étudié l’incidence et les types de seconds cancers.RésultatsAu total, 719 dossiers ont été examinés dont 94 (13 %) avaient un antécédent d’au moins un cancer. Pour les premiers cancers primitifs, 46 (49 %) étaient des cancers classant-SIDA (ADCs) et 48 (51 %) des cancers non-classant-SIDA (NADCs). Le sarcome de Kaposi (33 %) et le LNH (15 %) étaient les premiers cancers les plus fréquents. Parmi les premiers cancers qui étaient des ADCs, 15 % des seconds cancers étaient des LNH, 11 % des cancers du canal anal, 9 % de vessie et 9 % des lymphomes de Hodgkin. Parmi les premiers cancers qui étaient des NADCs, 38 % des seconds cancers étaient des cancers du poumon, 8 % de vessie, 8 % de la tête et cou et 8 % des LNH.DiscussionAvec le vieillissement des PVVIH, l’incidence des seconds cancers (et ultérieurs) devrait augmenter dans cette population. Le contrôle immuno-virologique doit être maintenu. Surveillance accrue, prévention précoce et programmes de dépistage devraient être proposés à toutes les PVVIH, même avec une charge virale VIH indétectable et/ou une restauration immunitaire.

International audience; IntroductionHIV is an exclusion criterion for most lung cancer (LC) trials, however LC is the most common non-AIDS-defined malignancy in people living with HIV (PLHIV), poorer prognosis than the general population. Circulating tumor DNA (ctDNA) was a prognostic marker in LC patients from the general population. This study assessed ctDNA’s prognostic value in PLHIV from a dedicated phase II trial.MethodsOverall, 61 PLHIV with advanced non-squamous non-small-cell lung cancer (NSCLC) participated in the IFCT Phase II trial evaluating first-line four-cycle carboplatin (Ca) AUC5 pemetrexed (P) 500 mg/m2 induction therapy every 3 weeks, followed by P maintenance therapy. Blood samples collected before treatment were analyzed to detect ctDNA using ultra-deep targeted next-generation-sequencing (NGS).ResultsAppropriate samples were available from 55 PLVIH and analyzed for ctDNA detection. Including 42 males (76.4 %), 52.9 years median age, 51 smokers (92.7 %), five with non-squamous NSCLC Stage III (9%), 50 Stage IV (91 %), and performance status (PS) 0−2. ctDNA was detected in 35 patients (64 %), 22 with high and 13 with low ctDNA levels. Overall, 77 % were positive for TP53, 29 % for KRAS, and 11 % for STK11 mutations, more than one alteration was detected in 43 % of samples. Multivariate analysis showed that positive ctDNA was significantly associated with shorter PFS (HR, 4.31, 95 %CI: 2.06−8.99, p

Importance Therapies targeting immune checkpoints, such as the programmed cell death 1 (PD-1) receptor, have become the standard-of-care for patients with non-small cell lung cancer (NSCLC), but people living with HIV (PLWH) were excluded from these studies. Objective To evaluate the efficacy and tolerability of nivolumab in PLWH with advanced NSCLC. Design The CHIVA2 study was a nonrandomized, open-label, phase 2 clinical trial in PLWH with previously treated advanced NSCLC. Setting National multicenter prospective study. Participants patients had viral load of Intervention Nivolumab was administered in second or third line, as monotherapy intravenously at 3 mg/kg every 2 weeks, until disease progression or limiting toxicity. Main Outcomes and Measures The primary endpoint was disease control rate, evaluated using the Response Evaluation Criteria in Solid Tumors, version 1.1. Adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results Sixteen patients with advanced NSCLC were enrolled: 14 (88 %) were men, median age was 58 years (range: 44−71), and all were smokers. The median duration of nivolumab treatment was 3.5 months (range: 0.5–26.5). The median follow-up was 23.6 months. Disease control rate was 62.5 % for 15 evaluable patients at 8 weeks (2 with partial response, 8 with stable disease, and 5 with disease progression). Twelve (75 %) patients had treatment-related adverse events, which were mild or moderate, except for one patient experiencing severe pruritus, onycholysis, and pemphigoid. There were no opportunistic infections or unexpected immune-related events. HIV viral load was stable during treatment. An increase in proliferating CD8+ and CD4+ T-cells was observed after 3 nivolumab cycles in a subgroup of 9 patients. Conclusions and Relevance Second/third-line nivolumab treatment was well-tolerated and beneficial in PLWH with NSCLC. Future trials should investigate immune checkpoint inhibitors in first-line settings. Trial Registration EudraCT.ema.europa.eu registration number: 2016−003796-22

Introduction: This study aimed at generating a new simplified prognostic score (SPS) using common clinical and biological variables to discriminate a limited number of subgroups of patients with SCLC differing by their overall survival (OS). Methods: The SPS was developed exploring the Montpellier University Hospital retrospective database of 401 patients over a 16-year period. All patients had received etoposide - platinum-based chemotherapy as first-line treatment. The SPS development took into account significant determinants of OS in the Cox model, weighted by their regression β coefficients. Validation of the consequent SPS has been done separately in a combined population of 213 patients accrued from two different published trials (NCT03059667 and NCT00930891). Results: The significant independent determinants of OS included the following: (1) American Joint Committee on Cancer TNM stage IV (hazard ratio [HR]: 2.52; 95% confidence interval [CI]: 1.91–3.33); (2) Eastern Cooperative Oncology Group performance status greater than 1 (HR: 2.27; 95% CI: 1.79–2.87); (3) the presence of liver metastases (HR: 1.66; 95% CI: 1.29–2.15); and (4) neutrophil-to-lymphocyte ratio greater than 4 (HR: 1.39; 95% CI: 1.11–1.92). The SPS generated with these four variables, segregated three groups (good, intermediate, and poor prognosis) with respective median OS of 26.9 months (95% CI: 20.1–38.9), 11.5 months (95% CI: 9.8–13.0), and 6.8 months (95% CI: 5.8–8.3; log-rank p < 10–4). Harrell's C statistic estimate was 0.68 ± 0.012, suggesting goodness of calibration. In the validation cohort, the SPS segregated the aforementioned three subgroups in a nearly similar manner, with respective median OS: 27.2, 12.3, and 8.6 months (log-rank p < 10–3; Harrell’s C statistic: 0.58 ± 0.02). Conclusions: The SPS is easy to calculate in real-life practice and efficiently discriminates three populations with different prognoses. This study deserves further validation of this score in patients with SCLC receiving immunochemotherapy.

Immunotherapy with immune checkpoint inhibitors (ICIs) represents a breakthrough in lung cancer treatment. The efficacy of monoclonal antibodies targeting the programmed cell death protein 1 (PD-1), its ligand L1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) pathways has been demonstrated in several randomized trials, resulting in significantly improved survival rates in lung cancer patients, especially those with non-small-cell lung cancer (NSCLC), compared to standard chemotherapy. Hence, new therapeutic options have been opened up for advanced-stage lung cancer patients. However, most clinical trials on ICIs conducted so far have either excluded patients with poor performance status (PS) or chronic infections like human immunodeficiency virus (HIV), or accrued only a minor proportion of elderly patients despite the lack of an upper age limit. Our review paper provides a brief summary on the ICI data obtained so far in these special populations. Further dedicated studies are urgently needed to enable us to draw definitive conclusions on the usefulness of ICI in these special patient populations. The combination of ICI and chemotherapy must also be further assessed. It would, additionally, be useful to determine reliable biomarkers that should help us identify those patients who are more likely to benefit from ICI therapy.

Resume Les complications liees aux chimiotherapies cytotoxiques et aux anti-angiogeniques sont globalement bien connues des cliniciens. A l’inverse, les inhibiteurs de points de controle immunitaire (ICI) ont fait emerger de nouveaux profils de toxicite, notamment les effets indesirables d’origine immunologique. Les toxicites tous grades confondus sont globalement moins importantes avec les ICI qu’avec les chimiotherapies. Toutefois, une bonne connaissance de ces toxicites permettra de mieux les depister et les traiter. Avec une prise en charge therapeutique adequate, la plupart des toxicites d’origine immunologique est reversible, en dehors de certaines atteintes endocriniennes, et les deces imputables sont exceptionnellement rares. La generalisation de l’utilisation des ICI en vie reelle s’accompagnera a l’avenir de l’emergence de plus en plus d’effets indesirables, ce qui impliquera d’optimiser leur prise en charge. Le traitement de ces toxicites repose sur l’arret du medicament en cause, la corticotherapie dont la posologie est adaptee en fonction du grade de severite des toxicites, et parfois pour certains grades 4 au recours a des immunosuppresseurs. Des recommandations europeennes et americaines ont ete publiees et sont facilement accessibles. La grande variete des effets indesirables immunologiques rend necessaire une approche multidisciplinaire avec une prise en charge collaborative entre les differents specialistes afin de permettre une gestion optimale de ces toxicites tout en poursuivant les ICI dans la grande majorite des cas.

Resume Les cancers du poumon (CP) sont des cancers frequents et de mauvais pronostic. Leur prise en charge diagnostique et therapeutique est complexe et multidisciplinaire. Dans le cadre du Plan cancer 2009-2013, l’Institut national du cancer (INCa) a publie une etude sur les delais de prise en charge du CP confirmant des variations en fonction de facteurs lies a la maladie mais egalement des variations liees a la structure de soins et la presence de disparites geographiques. Le Plan cancer 2014-2019 a dans ses objectifs de maitriser les delais de prise en charge et de fluidifier le parcours du patient atteint de CP. L’impact des delais de prise en charge du CP sur le pronostic des patients n’est pas clairement demontre. Il semblerait que dans les stades avances, un delai court entre la premiere imagerie suspecte et le premier traitement soit associe a un plus mauvais pronostic et qu’a l’inverse, des delais longs sont associes a une survie plus courte dans les stades localises. Les stades localises et la necessite d’examens complementaires sont des facteurs d’allongement des delais de prise en charge. Des parcours structures de diagnostic du CP et des postes d’infirmiere de coordination ont ete instaures pour fluidifier la filiere diagnostique. S’ils permettent de diminuer les delais de prise en charge, leur impact sur la survie n’a pas ete etudie.

RASSF1 gene methylation predicts longer disease-free survival (DFS) and overall survival (OS) in patients with early-stage non-small-cell lung cancer treated using paclitaxel-based neo-adjuvant chemotherapy compared to patients receiving a gemcitabine-based regimen, according to the randomized Phase 3 IFCT (Intergroupe Francophone de Canc&eacute, rologie Thoracique)-0002 trial. To better understand these results, this study used four human bronchial epithelial cell (HBEC) models (HBEC-3, HBEC-3-RasV12, A549, and H1299) and modulated the expression of RASSF1A or YAP-1. Wound-healing, invasion, proliferation and apoptosis assays were then carried out and the expression of YAP-1 transcriptional targets was quantified using a quantitative polymerase chain reaction. This study reports herein that gemcitabine synergizes with RASSF1A, silencing to increase the IAP-2 expression, which in turn not only interferes with cell proliferation but also promotes cell migration. This contributes to the aggressive behavior of RASSF1A-depleted cells, as confirmed by a combined knockdown of IAP-2 and RASSF1A. Conversely, paclitaxel does not increase the IAP-2 expression but limits the invasiveness of RASSF1A-depleted cells, presumably by rescuing microtubule stabilization. Overall, these data provide a functional insight that supports the prognostic value of RASSF1 gene methylation on survival of early-stage lung cancer patients receiving perioperative paclitaxel-based treatment compared to gemcitabine-based treatment, identifying IAP-2 as a novel biomarker indicative of YAP-1-mediated modulation of chemo-sensitivity in lung cancer.

In the recent past, we observed an increased risk of cancer in the population with human immunodeficiency virus (HIV) owing to the development of antiretroviral therapies that decreased mortality caused by HIV-specific infections. This particularly fragile population is frequently excluded from clinical trials, and up-to-date recommendations for these patients are lacking. Only few cases of patients with HIV suffering from cancer and undergoing first-line immunotherapy have been reported so far. Here, we report the largest known study of patients with HIV with NSCLC (five patients) undergoing first-line immunotherapy by pembrolizumab, after CANCERVIH group selection. Our results are consistent with those of previous case reports concerning safety of immunotherapy in patients with HIV, revealing no severe or fatal toxicity, opportunistic infections, or immune reconstitution inflammatory syndrome. Moreover, pembrolizumab did not seem to modify HIV viral parameters. We also evaluated the effectiveness of immunotherapy in these HIV-immunosuppressed patients: the average survival was 9.8 months, with three patients having rapid progression and two partial response. Nevertheless, besides safety and drug-to-drug interactions, the effectiveness of first-line immunotherapy in people living with HIV needs to be supported by larger studies.

Introduction La radiotherapie post-operatoire (RPO) est un sujet de discussion depuis la meta-analyse montrant que la RPO pouvait etre deletere en particulier chez les patients (pts) pN0 et pN1. Cependant, la question restait ouverte pour les pts pN2, d’autant que de nombreux changements ont eu lieu dans la prise en charge des pts traites pour un carcinome bronchique non a petites cellules (CBNPC) de stade IIIAN2. Methodes Lung ART est un essai de phase III randomise europeen comparant une RPO mediastinale (54 Gy/27–30 fractions) a l’absence de RPO. Les pts etaient eligibles s’ils etaient PS 0-2, avaient une resection complete avec exploration nodale, une maladie N2 averee; la CT (neo) adjuvante etait autorisee. Le critere principal etait la survie sans maladie (DFS). Les criteres d’evaluation secondaires comprenaient la toxicite, le controle local, les modalites de rechute, la survie globale (SG), et les seconds cancers. Resultats Entre aout 2007 et juillet 2018, 501 patients ont ete randomises apres chirurgie ou apres CT adjuvante, dont 427 dans IFCT-0503: 252 pts ont ete alloues au bras RPO, et 244 pts au bras temoin. L’âge median etait de 61 ans (intervalle = 36–85), 66 % d’hommes, adenocarcinome (73 %). La plupart des pts ont recu une CT (post-operatoire 77 %, pre-operatoire 18 %). Le suivi median est de 4,8 ans. La compliance en terme de RPO etait bonne: 7 pts l’ont interrompu. Une toxicite cardio-pulmonaire tardive de grade 3-5 a ete rapportee chez 47 pts (19,5 %) dans le bras RPO vs 19 (7,7 %) dans le bras controle: il n’y avait pas de difference en ce qui concerne les toxicites de grade 5. Le «Hasard Ratio (HR))» pour la DFS etait de 0,847 (IC a 95 % 0,67; 1,07); p = 0,156; la DFS mediane etait de 30,5 mois dans le bras RPO [24; 48] et de 22,8 mois dans le bras controle [17; 37]; La DFS a 3 ans etait de 47,11 % avec la RPO contre 43,8 % sans RPO. Le risque de rechute mediastinale est reduit de pres de moitie avec la RPO (46 % dans le bras controle versus 25 % dans le bras RPO). Le taux de SG a 3 ans etait de 66,48 % avec PORT contre 68,53 % sans PORT. Conclusion Lung ART est la premiere etude randomisee europeenne evaluant une RPO 3D apres resection complete, chez des patients selectionnes principalement par TEP et ayant recu une CT (neo) adjuvante. Le taux de DFS a 3 ans etait plus eleve que prevu dans les deux bras et la RPO etait associee a une augmentation non statistiquement significative de 15 % de la DFS parmi les pts operes de facon complete d’un CPNPC de stade IIIAN2.

Resume Les essais controles randomises (ECR) constituent la reference pour evaluer l’efficacite d’une intervention. Le developpement clinique du medicament s’est aligne a cette methodologie pour l’obtention d’une autorisation de mise sur le marche en imposant la realisation successive d’essais de phase I, II et III. Neanmoins, face a l’augmentation des couts humains et financiers et a la necessite de maintenir le niveau de remuneration des actionnaires de l’industrie pharmaceutique, les essais combines de phase I/II et II/III ont ete proposes afin de raccourcir la duree du developpement et de diminuer les couts. Par ailleurs, l’irruption de la medecine de precision issue de la recherche d’un couple biomarqueur predictif/therapie ciblee a rendu ethiquement difficile la poursuite des ECR dans cette situation et a permis de developper des nouveaux schemas d’essais therapeutiques comme les essais stratifies, basket, umbrella, adaptatifs et strategiques. Ces nouveaux schemas ont permis l’acces rapide a des AMM pour des maladies rares (dabrafenib+trimetinib/BRAFV600, crizotinib/ROS) mais ils ont egalement ete utilises dans le developpement initial de certaines immunotherapies. Leurs inconvenients sont : la multiplicite des bras ; la complexite de l’analyse statistique ; l’absence d’evaluation de l’effet de la molecule ciblee en population generale ; le faible effectif des malades inclus avec un risque d’ignorer des evenements indesirables rares ; l’absence de comparaison a un traitement de reference et finalement l’absence d’evaluation de l’impact du traitement sur la survie globale.

Resume Ces dernieres annees ont vu la decouverte dans les CBNPC d’alterations moleculaires agissant comme « drivers » oncogeniques et conferant une sensibilite a des traitements cibles, definissant ainsi l’addiction oncogenique. Ces progres concernent principalement les CBPNC non-epidermoides. Certaines anomalies donnent acces a des traitements pour lesquels une AMM est disponible. Il s’agit des mutations d’EGFR, de BRAF, des rearrangements d’ALK, et de ROS1. D’autres biomarqueurs anciens font toujours l’objet d’essais therapeutiques, et d’autres emergents sont prometteurs (mutations KRAS, HER2, PIK3CA, anomalies moleculaires de la voie MET) (amplifications du gene et mutations des sites d’epissage de l’exon 14), rearrangements de RET (et de NTRK). Plus recemment ont ete mis en evidence des biomarqueurs refletant l’etat d’activation du systeme immunitaire, predictifs de la sensibilite a certaines immunotherapies par inhibiteurs des points de controle (anti-PD1 ou anti-PD-L1). Ainsi, l’etude de l’expression de PD-L1 va devenir systematique car conditionnant des AMM de premiere et de deuxieme ligne. Il faut donc rechercher systematiquement les mutations d’EGFR, BRAF, KRAS, le rearrangement ALK et la surexpression de PD-L1 ; en cas de negativite de ceux-ci, sont ou devraient etre recherchees les anomalies de MET, ROS1, RET, NTRK.

International audience; ROS1 fusions are rare mutations that preferentially concern young and non-smoker women. The ROS1-rearranged protein conserves an intact tyrosine kinase domain, leading to the constitutive activation of the ROS1 tyrosine kinase function and of its downstream pathways, that are known to be involved in tumorigenesis. These molecular abnormalities have shown their oncogenic potential in animals’ models and in human, with an early effect on carcinogenesis. Several partners have been identified. Patients with non-small cell lung cancers (NSCLC) harbouring ROS1 alterations can receive specific targeted therapies. Indeed, crizotinib has recently been approved in France in advanced ROS1-rearranged NSCLC. We propose a review of the oncogenic role of ROS1 rearrangements, the different methods for its diagnosis, and the available treatments.; Les réarrangements de ROS1 sont des anomalies rares qui concernent plutôt des femmes jeunes, non ou peu fumeuses. La protéine ROS1 issue de ces réarrangements conserve un domaine tyrosine kinase intact, ce qui entraîne l’activation constitutive de la kinase et des voies de signalisation d’aval, connues comme impliquées dans la tumorigenèse. Ces anomalies ont montré leur potentiel oncogénique dans les modèles animaux mais également chez l’homme, intervenant de manière précoce dans la carcinogenèse. Plusieurs partenaires différents ont été identifiés, et les tumeurs portant cette altération moléculaire peuvent faire l’objet de thérapeutiques spécifiques dans le cancer bronchique non à petites cellules (CBNPC). Ainsi, le crizotinib a récemment obtenu une autorisation de mise sur le marché (AMM) dans le traitement du CBPNC avancé ROS1 positif. Cet article effectue une revue des données concernant le rôle oncogénique de ROS1, les différentes modalités diagnostiques de l’altération et les traitements actuellement disponibles pour cibler ces tumeurs.

Summary Following the introduction of highly active antiretroviral treatments (HAART), patients infected with HIV have experienced significant survival improvement. Since the beginning of the HIV epidemic, three types of cancer constitute a diagnosis of AIDS (defined as AIDS malignancies) in HIV-positive patients: Kaposi sarcoma, non-Hodgkin lymphoma and, since 1993, cervical cancer. However, in the late 1990s, population-based cohort studies revealed higher rates of certain other cancers (defined as non-AIDS related malignancies). This chapter discusses the incidence, aetiology, screening, pathology, diagnosis, and follow-up of these HIV-related neoplasms. Hodgkin lymphoma, anal carcinoma, lung carcinoma and hepatocellular carcinoma, are the most common non-AIDS-defining malignancies (ADMs). Lung cancer is the only frequent cancer in HIV-infected patients not known to be associated with viral infection. Anal cancer is emerging as an important cause of mortality among people with a longer duration of HIV infection. Keywords: AIDS-defining malignancies; anal carcinoma; cervical cancer; HIV-related neoplasms; Hodgkin lymphoma; Kaposi sarcoma; lung cancer; non-Hodgkin lymphoma

PurposeHIV infection is an exclusion criterion in lung cancer trials. This multicenter phase II trial aimed to assess feasibility, efficacy and safety of first-line carboplatin plus pemetrexed (CaP) followed by pemetrexed (P) maintenance in people living with HIV (PLHIV) with advanced non-squamous non-small cell lung cancer (NS-NSCLC).MethodsFour cycles of CaP were followed by P-maintenance therapy in patients with Eastern Cooperative Oncology Group performance status (PS) ≤2. The primary objective was a disease control rate (DCR) ≥30% after 12 weeks.ResultsOf the 61 PLHIV enrolled 49 (80%) had a PS 0–1, 19 (31%) brain metastases. Median CD4 lymphocyte count was 418 cells·µL−1(range: 18–1230), median CD4 lymphocyte nadir 169.5 cells·µL−1(1–822); 48 patients (80%) were virologically controlled. Four-cycle inductions were achieved by 38 patients (62%), and 31 (51%) started P maintenance [median of 4.1 cycles (range: 1–19)]. The 12-week DCR was 50.8% (95%CI: 38.3;63.4) and partial response rate 21.3%. Median PFS and OS were respectively 3.5 (95%CI: 2.7;4.4) and 7.6 months (5.7;12.8). Patients with PS 0–1 had the longest median PFS (4.3 months, 95%CI: 3.1;5.2) and OS (11.9 months, 95%CI: 6.4;14.3). During induction, CaP doublet was well tolerated apart from grade 3–4 hematologic toxicities (neutropenia, 53.8%; thrombocytopenia, 35.0%; anemia, 30.0%). Two fatal treatment-related sepsis were reported. No opportunistic infections were experienced.ConclusionIn PLHIV with advanced NS-NSCLC, first-line 4-cycle CaP induction followed by P maintenance was effective and reasonably well-tolerated. Further studies should evaluate combination strategies of CaP with immunotherapy in PLHIV.

International audience; Objective: To report efficacy and tolerance of nivolumab or pembrolizumab, PD-1 inhibitors, in people living with HIV (PLWHIV) and cancer.Design: Series of PLWHIV cancer patients treated with anti-PD1 agents in real-life clinical practice.Methods: From May 2014 to January 2019, 575 HIV-infected patients have been discussed in the French CANCERVIH national multidisciplinary board and included in the network database. Twenty-three patients were treated with immune checkpoint inhibitors in daily practice. We report the demographic characteristics, CD4+ T-cell counts, HIV viral loads, safety and efficacy data of these 23 PLWHIV treated in routine practice with nivolumab or pembrolizumab for nonsmall cell lung cancer (n = 21), melanoma (n = 1) and head and neck cancer (n = 1) retrospectively collected from the database CANCERVIH network. The median CD4+ T-cell count at treatment initiation was 370 cells/μl (IQR: 125–1485). HIV viral load was undetectable in all patients.Results: As of 29 April 2019, with a median follow-up of 10.8 months (2.0–27.7), the median number of injections was 6 (IQR: 4–18). Only two grade 3 adverse reactions were reported (no toxic deaths or immune-related deaths). Among the 23 patients, a partial response was observed in five patients (22%), a stabilization for five (22%) and a progression in 13 (57%). Only one patient experienced a positive HIV viral load, but this occurred following ART interruption.Conclusion: Treatment with PD-1 inhibitors seems to have an efficacy signal and be well tolerated in PLWHIV, including impact on CD4+ lymphocyte count and HIV load, that should be monitored during treatment course (regarding real-life experience).

Introduction L’immunotherapie par anti-PD-1/L1 est desormais un standard de traitement en 1re ou en 2e ligne chez les malades avec un CBNPC avance sans addiction oncogenique. Les PVVIH etant exclues de presque toutes les etudes d’enregistrement, nous avons realise un essai de phase II evaluant l’innocuite et l’efficacite du Nivolumab (N) dans cette population. Methodes Pouvaient etre inclus les PVVIH ayant: 1) une charge virale VIH Resultats Seize PVVIH (87,5% d’hommes), de 58 ans d’âge median (44–71), ont ete recrutes entre 12/2017 et 07/2019. 94% etaient des fumeurs, 81% avaient un ECOG PS 0–1. La duree mediane depuis le diagnostic du VIH etait de 24 ans (3–39) avec avant la mise sous Nivolumab des a CD4 384 cellules/μL (187–778) et une charge virale VIH (CV) a 25 copies/ml. 62,5% avaient un adenocarcinome, 31% un epidermoide et 6,5% un CBNPC autre. L’expression de PD-L1 etait negative pour 9/14 tumeurs (64%) et positif dans 5 (36%) avec ≥ 50% de cellules tumorales positive chez 3. Les patients ont recu du N en 2e (69%) et en 3e ligne (31%) pour une duree mediane de 3,5 mois (0,5–22,8). La maladie etait controlee a 8 semaines chez 62,5% (IC a 95%: [38,8–86,2]) des malades avec 12,5% de reponses partielles et 50% de maladies stables. La SSP mediane et la SG etaient de 3,4 (IC a 95%: 1,77–5,49) et de 14 (IC a 95%: 2,17–NR). Les evenements indesirables lies au traitement etaient de grade 1 ou 2 chez 69% et un seul a presente un grade 3 (pemphigoide au cycle 27). Aucune infection opportuniste ou evenement clinique immunitaire inattendu n’ont ete observes. La numeration des CD4 sanguins et la charge virale du VIH n’ont pas ete modifiees pendant le traitement par N. Conclusion Chez les PVVIH atteints de CBNPC, le Nivolumab administre apres une chimiotherapie a base de platine est associe a une efficacite et une tolerance similaires a celles des essais d’enregistrement.

Introduction Le traitement pre-operatoire par inhibiteurs des points de controle immunitaire peut etre benefique pour les CBNPC de stade precoce. IFCT-1601 IONESCO est un essai multicentrique evaluant la faisabilite du durvalumab neoadjuvant. Methodes Les patients ayant un CBNPC resecable de stade IB > 4cm-IIIA non N2 (TNM 8e edition) recevaient 3 cures de durvalumab 750 mg (J1, 15, 29) avant la chirurgie. Le critere principal etait le % de resection chirurgicale complete (R0); les criteres d’evaluation secondaires etaient la tolerance, la survie globale (SG), la survie sans recidive (SSR), le temps entre la premiere perfusion et l’intervention chirurgicale, le taux de reponse (RECIST 1.1), le taux de reponse pathologique majeure (MPR). Resultats 50 pts ont ete inclus (04/2017 - 08/2019). 46 patients sont eligibles. 70 % hommes, âge median, 61 ans; tous ECOG PS 0-1; 94 % (ex-)fumeurs; 25 adenocarcinomes, 21 epidermoides; stades IB/IIA/IIB/IIIA n = 5/14/29/2. Parmi les 46 pts eligibles, 9 ont eu une pneumonectomie, 31 une lobectomie, 3 une bilobectomie et 3 une thoracotomie exploratrice (2 carcinoses pleurales; 1 envahissement de l’œsophage). L’etude a ete interrompue en raison d’un exces de mortalite postoperatoire a 90 jours (4 deces, 9 % avec 1 deces brutal a domicile; 1 fistule tracheale, 1 complication chirurgicale et une detresse respiratoire aigue). 3 des 4 pts decedes presentaient des comorbidites cardiovasculaires (3 hypertensions arterielles; 1 maladie arterielle peripherique; 1 cardiopathie ischemique), ou autres (1 BPCO grave; 1 diabete). 41 pts etaient R0 (90 %). Il n’y a pas eu d’EI de grade 3-5 lies au durvalumab. 4/46 pts presentaient une PR, 36 SD et 6 PD. Le temps median entre la premiere perfusion et l’intervention chirurgicale etait de 37 jours (29–46). %SG a 12 m [IC a 95 %]: 89,1 % [75,8–95,3]; %SSR a 12 m [IC a 95 %]: 78,2 % [63,3–87,6]. Le taux de MPR etait de 18,6 % avec 3 pts en reponse pathologique complete. Il existait une correlation significative entre les taux de MPR et la reponse radiologique (p = 0,028). Les pts avec MPR avaient une SSR significativement plus longue (SSR de 12 m: % [IC 95 %] 100 % contre 77,1 % [59,5–87,9], p = 0,045). Conclusion L’essai a ete arrete en raison d’une mortalite postoperatoire excessive a 90 jours. Les deces etaient dus a des complications postoperatoires probablement liees a des comorbidites et non a une toxicite directe du durvalumab. Les taux de MPR etaient significativement correles a la reponse radiologique et a la SSR.

International audience; A shift in mortality and morbidity has been observed in people living with human immunodeficiency virus (PLWHIV) from acquired immunodeficiency syndrome (AIDS) to non-AIDS diseases. Lung cancer has the highest incidence rates among all the non-AIDS-defining malignancies and is associated with mortality rates that exceed those of other cancers. Strategies to increase lung cancer survival in PLWHIV are needed. Lung cancer screening with chest LDCT has been shown to be efficient in the general population at risk. The objective of this review is to discuss lung cancer screening with chest computed tomography in PLWHIV. Lung cancer screening in PLWHIV is feasible. Whether PLWHIV could benefit from an age threshold for screening that is earlier than the minimum age of 55 years usually required in the general population still needs further investigation. Studies evaluating smoking cessation programs and how they could be articulated with lung cancer screening programs are also needed in PLWHIV.

International audience; Non–small-cell lung cancer (NSCLC) is the most common non-acquired immune deficiency syndrome-related malignancy responsible for death. Mutational status is crucial for choosing treatment of advanced NSCLC, yet no data is available on the frequency of epidermal growth factor receptor (EGFR) and Kirsten ras (KRAS) mutations and their impact on NSCLC in human immunodeficiency virus (HIV)-infected patients (HIV-NSCLC).All consecutive HIV-NSCLC patients diagnosed between June 1996 and August 2013 at two Paris university hospitals were reviewed, with tumor samples analyzed for EGFR and KRAS mutational status.Overall, 63 tumor samples were analyzed out of 73HIV-NSCLC cases, with 63% of advanced NSCLC. There were 60 non-squamous and nine squamous cell carcinomas, with EGFR and KRAS mutations identified in two (3.3%) and seven (11.5%) tumors, respectively. The proportion of KRAS mutations was 29% if solely the more sensitive molecular techniques were considered. The two patients with advanced adenocarcinoma harboring EGFR mutations exhibited lasting partial response to EGFR-tyrosine kinase inhibitors. Overall survival for patients with advanced NSCLC were >30 months for those with EGFR mutations

Recently, developments of therapies that target abnormally activated signaling pathways are increasing for patients with non-small cell lung cancer. EGFR mutations are found in about 10% of lung cancers, especially in adenocarcinoma, women and non-smokers. Three EGFR inhibitors (erlotinib, gefitinib and afatinib) received a European marketing authorization for up to first line treatment of EGFR mutated NSCLC. Effectiveness of EGFR inhibitors is higher than conventional chemotherapy. Third generation EGFR inhibitors (rociletinib, AZD9291) are effective for patients who develop a resistance mutation such as T790M resistance mutation; they obtained temporary authorization for use in France in 2015. The EML4-ALK translocation is found in about 5% of NSCLC and more particularly in adenocarcinoma of young non-smoking patients. Crizotinib is a new therapeutic standard in ALK translocated NSCLC in second line. Ceritinib is a 2nd generation ALK inhibitor which received a European marketing authorization for up to treatment of ALK translocated NSCLC after progression with crizotinib. INCA supports ACSe program evaluating the efficacy of crizotinib in NSCLC amplified for MET or translocated for ROS1 and ACSe program evaluating the efficacy of vemurafenib in tumors non melanoma mutated V600E BRAF. The role of other biomarkers such as KRAS, BRAF, HER2 and PI3KCA mutations remains to be defined in NSCLC.

Resume Le bilan initial doit repondre a quatre imperatifs : apprecier l’etat clinique, obtenir une preuve diagnostique, definir le stade cTNM et, en cas de resecabilite, l'operabilite du patient. Les modalites du bilan locoregional basees sur les recommandations nationales et internationales sont resumees. L'examen clinique reste essentiel. Le scanner thoracique avec injection de produit de contraste iode est systematique, sauf contre-indication. La taille de la tumeur, son extension pleurale, parietale, endobronchique et mediastinale directe doivent etre precisees. Les performances du scanner pour predire l'envahissement ganglionnaire mediastinal sont mediocres (sensibilite [Se] = 61 % et specificite [Sp] = 79 %). La tomographie par emission de positons-tomodensitometrie (TEP-TDM) n'est pas indiquee en 1re intention, mais elle est indispensable chez un patient potentiellement eligible a un traitement curatif. Ses performances pour definir le statut mediastinal sont meilleures (Se = 80 % et Sp = 80-90 %). En l'absence d'un envahissement mediastinal massif, des explorations invasives sont indiquees en cas de ganglion ≥ 10 mm ou infracentimetrique fixant le fluorodesoxyglucose (FDG) ou devant la presence d'une adenopathie hilaire, d'une tumeur centrale ou > 3 cm. L’echoendoscopie bronchique et/ou œsophagienne est realisee en 1re intention, avant la mediastinoscopie. Les stades III doivent etre classes en potentiellement resecables, non resecables, potentiellement resecables avec risque de resection incomplete. Le respect des recommandations et une organisation adequate optimisent la prise en charge.

Resume Les cellules inflammatoires et immunitaires, les fibroblastes et les cellules endotheliales forment le micro-environnement de la tumeur. L'immunite innee favorise l'inflammation et constitue la premiere ligne de defense non specifique contre les agents pathogenes ou les cellules ≪ transformees ≫. Elle se compose principalement des mastocytes, des macrophages, des neutrophiles et des cellules naturelles tueuses NK (Natural Killer). L'inflammation chronique est le lit du cancer. De nombreuses maladies inflammatoires chroniques sont associees a un surrisque de cancer. En ce qui concerne le cancer du poumon, l'inflammation chronique observee au cours de la BPCO, de l'emphyseme ou de la fibrose pulmonaire idiopathique est associee au developpement d'un cancer bronchique. Dans cet article, nous presentons les effets proet antitumoraux de l'inflammation liee au systeme immunitaire inne dans le cancer bronchique. La place du systeme immunitaire specifique est decrite dans un autre chapitre. Au cours de la progression tumorale, les cellules cancereuses vont pouvoir utiliser et/ou contourner les signaux issus des cellules inflammatoires afin de favoriser la proliferation tumorale, l'invasion tissulaire et la formation de metastases. Il n'y a pas d'agents therapeutiques disponibles qui ciblent specifiquement l'inflammation.

Resume Il n'y a pas de bonne definition de l'innovation therapeutique. Dans le domaine du cancer du poumon, il semble bien que ce soit la quantite de vie gagnee qui definisse le mieux l'innovation therapeutique pour le grand public comme pour les professionnels de sante. Les medicaments doivent subir un developpement long et multi-etape pour arriver jusqu’a leur autorisation de mise sur le marche (AMM). Ce developpement est tres couteux pour les industriels, et l'innovation therapeutique pese lourd economiquement pour la societe, du fait du remboursement des traitements. Le concept de therapeutique ciblee couplee a son biomarqueur predictif a permis de rationaliser et de raccourcir les delais d'obtention des AMM, mais le nivolumab, anticorps anti-PD1, a obtenu tres rapidement son AMM dans le traitement des carcinomes epidermoides, sans la necessite d'un biomarqueur predictif. Les agences de regulation ont egalement mis en place des procedures d’evaluation acceleree des molecules, comme les AMM conditionnelles. L'explosion des techniques de biologie moleculaire a aussi permis de decouvrir un grand nombre d'addictions oncogeniques rares, mais parfois partagees par differents cancers, menant a de nouvelles sortes d'essais therapeutiques de type basket, afin d'en evaluer l'efficacite. Finalement, la France propose des dispositifs reglementaires uniques a travers ses autorisations temporaires d'utilisation (ATU) et recommandations temporaires d'utilisation (RTU) pour offrir a tous – ou presque – un acces aux innovations therapeutiques.

Resume L'incidence et la mortalite par cancer chez les personnes vivant avec le VIH (PVVIH) ont evolue depuis les annees 1990 : le VIH ne represente plus qu'un quart des deces dans cette population. Cette evolution est liee a l’emergence de combinaisons antiretrovirales tres actives, ayant permis d'allonger l'esperance de vie des patients et de diminuer les complications liees au virus. Les cancers sont de ce fait devenus la premiere cause de mortalite. Du fait de l'immunodepression et du tabagisme important, le risque de cancer broncho-pulmonaire (CBP) est deux a trois fois plus eleve que celui de la population generale. Il est le plus frequent des cancers non classant sida et represente la premiere cause de deces par cancer. L’âge de survenue chez les PVVIH est plus jeune, et le pronostic plus mauvais. Le traitement du CBP chez les PVVIH est plus complexe que dans la population generale, en raison d'interactions medicamenteuses avec les antiretroviraux (ARV), de l'agressivite tumorale et de comorbidites particulieres. Une meilleure connaissance de la biologie moleculaire, l'immunotherapie et le depistage sont des axes de recherche majeurs pour ameliorer la survie des PVVIH atteintes de CBP. Pour toutes ces raisons, l'inclusion dans les essais therapeutiques dedies constitue une priorite.

Introduction L’immunotherapie est recemment devenue un standard therapeutique des CBNPC localement avances et metastatiques. Des etudes recentes suggerent que la RT pourrait stimuler la reponse immunitaire antitumorale. L’objectif de cette etude etait d’evaluer l’impact d’une RT prealable ou concomitante a une immunotherapie dans les CBNPC metastatiques. Methodes Cette etude retrospective monocentrique concerne 194 CBNPC metastatiques diagnostiques dans un CHU entre 01/2015 et 08/2018 et traites par un anti-PD1. Le critere de jugement principal etait la survie sans progression (SSP) a partir du debut de l’immunotherapie. Les criteres secondaires etaient la survie globale a partir du debut de l’immunotherapie (SG) et la tolerance. Resultats Au total, 65 patients (pts) avaient recu une RT prealable ou concomitante a l’immunotherapie (RT + ) et 129 n’en avaient pas recu (RT − ). Les patients RT+ presentaient davantage de sites metastatiques (p = 0,015), de metastases osseuses (p Conclusion La RT prealable ou concomitante a l’immunotherapie semble etre un facteur de bon pronostic sur la SSP et la SG chez les pts traites par immunotherapie dans les CBNPC metastatiques. Des etudes prospectives sont en cours pour confirmer cet impact.

Introduction Les delais de prise en charge, l’interface avec la ville et les pratiques avancees des IDE sont des objectifs du plan cancer 2014–2019 ; un parcours de diagnostic rapide structure avec une IDEC, soutenu par la direction a ete mis en place en mai 2016. Les demandes adressees au service sont centralisees sur un mail generique coordonne par la secretaire afin de faciliter le tri medical ; les patients sont inscrits en consultation sur des plages reservees ; le bilan en HDJ est programme 48 h a 72 h apres si le patient est ambulatoire ; le parcours de soins est coordonne par l’IDE jusqu’a l’annonce. Une prise en charge sociale, nutritionnelle et psychologique est organisee des la premiere prise de contact. Methodes Etude epidemiologique observationnelle retrospective des delais de prise en charge des patients vus a la consultation specialisee entre mai 2016 et decembre 2018. Resultats Au total, 677 demandes de prise en charge ont ete adressees a la secretaire de coordination et 508 patients ont ete vus en consultation « opacite suspecte » apres un tri medical. Le delai d’acces a la consultation etait Conclusion Les delais de prise en charge du centre de diagnostic sont conformes aux bonnes pratiques ; le binome secretaire - IDEC est un atout pour l’etablissement, le medecin et le patient car il permet de repondre rapidement a la demande en proposant un parcours structure en collaboration avec les plateaux techniques. Ces nouveaux metiers offrent des opportunites professionnelles aux IDE. Ils peuvent s’inscrire egalement dans le cadre des pratiques avancees.

Summary Background Despite recent progress, non-small cell lung cancer (NSCLC) first-line treatment remains a platinum-based doublet in most cases. No guidelines exist beyond third line. Chemotherapy rechallenge is an option, but little data is available in NSCLC. Our study aims to describe patients who underwent chemotherapy rechallenge while assessing its efficacy and safety. Methods Consecutive patients with advanced-stage NSCLC receiving first-line treatment in Tenon hospital in 2011 were included, with a 5-year follow-up. Patients were analyzed according to chemotherapy rechallenge or not. Chemotherapy rechallenge was defined as re-initiation of a previously administered chemotherapy agent at any point in the treatment sequence, with at least one treatment regimen between first use and rechallenge. Results Of 149 patients, 18 underwent chemotherapy rechallenge (12%). They were younger (56 vs. 61 years, P = 0.04), mostly women (61% vs. 30%, P = 0.02), with lepidic adenocarcinoma (23% vs. 3.5%, P = 0.03), a better general state of health (100% performance status 0–1 vs. 74%, P = 0.04), and fewer cardiovascular comorbidities (16% vs. 42%, P = 0.04). They were more likely to have received a receptor tyrosine kinase inhibitor treatment (89% vs. 43%, P = 0.0003). Progression-free survival was longer at first use than at rechallenge (median 9.2 vs. 2.7 months, P = 0.002). No increased toxicity was observed at rechallenge compared to first use. Finally, a subsequent line of treatment was given after rechallenge in 61% of the patients. Conclusion Patients eligible for chemotherapy rechallenge were those with good prognostic factors. Chemotherapy rechallenge may provide a well-tolerated additional line of treatment, with decreased efficacy compared to its first application.

International audience; Since the era of combined antiretroviral therapy, life expectancy of people living with HIV has been improved and is associated with a change in causes of death. Cancer, both AIDS-defining or non-AIDS-defining cancers, has become the leading cause of death in people living with HIV associated with an increase in the incidence of some cancers compared to the general population. Epidemiology and the identification of risk factors is a crucial issue, particularly to determine the most appropriate prevention and screening strategies in this population. In the absence of dedicated clinical trials, the cancer management in these patients is based on general recommendations, with specific attention to comorbidities and drug interactions. In addition, the development of new innovative therapies such as immunotherapy with inhibitory antibodies of immune checkpoints receptor represents a hope for the patient care, both infected or not with HIV. In this context, the establishment of the national network CancerVIH makes sense, allowing the establishment of multi-disciplinary consultation meetings involving all the practitioners involved in the care of these patients with cancer, as well as the constitution of a national cohort and the promotion of dedicated trials, to improve and optimize the management for these patients.

International audience; Since the era of combined antiretroviral therapy, life expectancy of people living with HIV has been improved and is associated with a change in causes of death. Cancer, both AIDS-defining or non-AIDS-defining cancers, has become the leading cause of death in people living with HIV associated with an increase in the incidence of some cancers compared to the general population. Epidemiology and the identification of risk factors is a crucial issue, particularly to determine the most appropriate prevention and screening strategies in this population. In the absence of dedicated clinical trials, the cancer management in these patients is based on general recommendations, with specific attention to comorbidities and drug interactions. In addition, the development of new innovative therapies such as immunotherapy with inhibitory antibodies of immune checkpoints receptor represents a hope for the patient care, both infected or not with HIV. In this context, the establishment of the national network CancerVIH makes sense, allowing the establishment of multi-disciplinary consultation meetings involving all the practitioners involved in the care of these patients with cancer, as well as the constitution of a national cohort and the promotion of dedicated trials, to improve and optimize the management for these patients.

OBJECTIVE Immunotherapies targeting the programmed cell death-1 (PD-1)/PD-ligand 1 (PD-L1) checkpoint improved prognosis in lung cancer. PD-1/PD-L1 status, however, has not been investigated in human immunodeficiency virus (HIV)-positive patients. This study assessed PD-L1 status and tumor immune-cell infiltration in nonsmall cell lung cancer (NSCLC) in HIV patients. METHODS Consecutive HIV patients treated between 1996 and 2014 were enrolled. PD-L1 tumor expression was assessed using immunohistochemistry with two antibodies (clones 5H1 and E1L3N), and tumor immune-cell infiltration with CD3, CD4, CD8, CD20, CD163, and MPO. PD-L1 expression and immune infiltration results were compared with those of 54 NSCLCs from unknown HIV status patients. RESULTS Thirty-four HIV-positive patients were evaluated: predominantly men (88.2%) (median age: 51.1 years) presenting stage IV (38.2%) adenocarcinomas (76.5%). The median blood CD4 count was 480 cells/μL (86-1120) and 64% exhibited undetectable viral load. The PD-L1 score (percentage of positive cells × intensity) was higher in HIV-positive than HIV-undetermined patients with the E1L3N clone [median (range) 0 (0-150) versus 0 (0-26.7), P = 0.047], yet not with the 5H1 clone [0 (0-120) versus 0 (0-26.7) P = 0.07, respectively]. PD-L1 expression frequency did not differ between both cohorts (18.7 versus 9.3% using E1L3N and 10 versus 5.6% using 5H1 clone, respectively). There were significantly greater cytotoxic T-cell (P

Introduction This study compared the efficacy of docetaxel alone vs. docetaxel plus cisplatin/carboplatin in resected NSCLC patients relapsing after preoperative, adjuvant, or perioperative platinum-based chemotherapy. Materials and methods Patients were randomly assigned to receive docetaxel plus cisplatin/carboplatin (Arm A) or docetaxel alone (Arm B). Primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate at 6 weeks, toxicity, quality of life, and overall survival (OS). Results From November 2007 to August 2012, 88 patients were enrolled. Due to an unexpectedly slow accrual, the trial was prematurely stopped. Adding platinum to docetaxel caused a non-significant increase in PFS. Median PFS was 8.0 months (95% CI: 5.3–10.4) for Arm A vs. 5.6 months (95% CI: 4.0–7.3) for Arm B (HR: 0.71, 95% CI: 0.45–1.1, p =0.15). Median OS was 16.0 months (95% CI: 10.1–23.9) for Arm A vs. 12.4 months (95% CI: 8.2–19.6) for Arm B. In pre-planned subgroup analyses, a time to recurrence ≥12 months and non-squamous histology favorably influenced OS (HR: 0.51, 95% CI: 0.29–0.91, p =0.02 and HR: 0.54, 95% CI: 0.33–0.91, p =0.02, respectively). There were no unexpected adverse events, and Grade 3–4 toxicity was comparable in both groups. Conclusions Our study failed to demonstrate significant PFS improvement with the docetaxel-platinum doublet compared to single-agent docetaxel. The 3.6-month improvement in OS with the cisplatin-based doublet proves, however, appealing and merits further investigation.

Although the decline in cancer mortality rates with the advent of combination antiretroviral therapy (cART) in HIV-infected individuals can be mostly explained by a decrease in cancers incidence, we looked here if improved survival after cancer diagnosis could also contribute to this decline. Survival trends were analyzed for most frequent cancers in the HIV-infected population followed in the French Hospital Database on HIV: 979 and 2,760 cases of visceral and non-visceral Kaposi's sarcoma (KS), 2,339 and 461 cases of non-Hodgkin lymphoma (NHL) and Hodgkin's lymphoma (HL), 446 lung, 312 liver and 257 anal cancers. Five-year Kaplan–Meier survival rates were estimated for four periods: 1992–1996, 1997–2000, 2001–2004 and 2005–2009. Cox proportional hazard models were used to compare survival across the periods, after adjustment for confounding factors. For 2001–2004, survival was compared to the general population after standardization on age and sex. Between the pre-cART (1992–1996) and early-cART (1997–2000) periods, survival improved after KS, NHL, HL and anal cancer and remained stable after lung and liver cancers. During the cART era, 5-year survival improved after visceral and non-visceral KS, NHL, HL and liver cancer, being 83, 92, 65, 87 and 19% in 2005–2009, respectively, and remained stable after lung and anal cancers, being 16 and 65%, respectively. Compared with the general population, survival in HIV-infected individuals in 2001–2004 was poorer for hematological malignancies and similar for solid tumors. For hematological malignancies, survival continues to improve after 2004, suggesting that the gap between the HIV-infected and general populations will close in the future.

Resume L’infection par le VIH est associee a une augmentation du risque de cancer, qu’il soit classant sida (maladie de Kaposi, lymphomes non hodgkinien, cancer du col uterin) ou non-classant sida. Si l’avenement des traitements antiretroviraux hautement actifs a diminue l’incidence des lymphomes non hodgkinien et de la maladie de Kaposi, les cancers non classants, tels que le cancer broncho-pulmonaire, l’hepatocarcinome, le cancer du canal anal ou bien les cancers cutanes, restent une cause importante de morbidite et de mortalite dans la population infectee par le VIH. La presentation clinique est souvent differente de celle de la population non infectee par le VIH, avec parfois un diagnostic plus tardif, une pathologie plus agressive et des comorbidites associees telles que l’immunodepression, responsables d’un pronostic souvent plus pejoratif. De nombreuses etudes se sont interessees au traitement de ces neoplasies associees a l’infection VIH, mais il n’existe pas encore a l’heure actuelle de recommandations precises sur le plan therapeutique. Une attention toute particuliere est a porter sur les interactions entre les traitements antiretroviraux et la chimiotherapie notamment via le cytochrome P 450. A ce titre, un reseau de soins appartenant au groupe des «cancers rares» dont le cœur de l’organisation repose sur une reunion de concertation pluridisciplinaire nationale (CANCERVIH) a ete mis en place en 2013grâce a l’Institut national du cancer (INCa). L’objectif de cette revue est de presenter une actualite scientifique concernant certains cancers associes a l’infection par le VIH, dans leurs aspects cliniques et dans la specificite de leur prise en charge therapeutique.

Until 1996, AIDS was the leading cause of deaths from HIV infection. In 2010, because of introduction of powerful antiretroviral therapies, AIDS represented less than 25% of deaths. Cancer has become the leading cause of death in this population, and, because of smoking and immunosuppression, lung cancer risk is more important than in general population. Furthermore, treatment is more difficult, due to potential interactions between antiretroviral and anticancer therapies, to comorbidities and to tumor aggressiveness. Research will focus on molecular biology, immunotherapies and lung cancer screening in order to improve survival of HIV patients with lung cancer. For all these reasons, HIV patients must be included in clinical trials.