Cost effectivenes of erlotinib versus chemotherapy for first-line treatment of non small cell lung cancer (NSCLC) in fit elderly patients participating in a prospective phase 2 study (GFPC 0504)

BACKGROUND: The median age of newly diagnosed patients with non-small cell lung cancer (NSCLC) is 67 years, and one-third of patients are older than 75 years. Elderly patients are more vulnerable to the adverse effects of chemotherapy, and targeted therapy might thus be a relevant alternative. The objective of this study was to assess the cost-effectiveness of erlotinib followed by chemotherapy after progression, compared to the reverse strategy, in fit elderly patients with advanced NSCLC participating in a prospective randomized phase 2 trial (GFPC0504). METHODS: Outcomes (PFS and overall survival) and costs (limited to direct medical costs, from the third-party payer perspective) were prospectively collected until second progression. Costs after progression and health utilities (based on disease states and grade 3–4 toxicities) were derived from the literature. RESULTS: Median overall survival, QALY and total costs for the erlotinib-first strategy were respectively 7.1 months, 0.51 and 27 734 €, compared to 9.4 months, 0.52 and 31 688 € for the chemotherapy-first strategy. The Monte Carlo simulation demonstrates that the two strategies do not differ statistically. CONCLUSION: In terms of cost effectiveness, in fit elderly patients with NSCLC, erlotinib followed by chemotherapy compares well with the reverse strategy

A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective

International audienceOBJECTIVES: Adjuvant chemotherapy with vinorelbine plus cisplatin (VC) improves survival in resected non-small-cell lung cancer (NSCLC), but has negative impact on quality of life (QoL). In advanced NSCLC, gemcitabine plus cisplatin (GC) and docetaxel plus cisplatin (DC) exhibit comparable efficacy, with possibly superior QoL compared to VC. This trial investigated these regimens in the adjuvant setting. METHODS: Patients with Stage IB to III NSCLC were eligible following standardized surgery. Overall, 136 patients were included, with 67 and 69 assigned to the GC and DC arms, respectively. Cisplatin (75 mg/m(2), Day [D] 1) plus gemcitabine (1250 mg/m(2), D1 and D8) or docetaxel (75 mg/m(2) D1) were administered for three cycles. Primary end-point was QoL (EORTC QLQ-C30), with the study designed to detect a 10-point difference between arms. Overall survival, safety and cost were secondary end-points. RESULTS: No between-group imbalance was observed in terms of patient characteristics. At inclusion, global health status (GHS) scores (/100) were 63.5 and 62.7 in GC and DC, respectively (P = 0.8), improving to 64.5 and 65.4 after 3 months (P = 0.8). No significant difference in functional or symptoms scores was observed between the arms except for alopecia. Grade 3/4 haematological and non-haematological toxicities were found in 33.8 and 21.7% (P = 0.11), and 33.8 and 26.1% (P = 0.33) of patients, in GC and DC, respectively. At 2 years, 92.9 and 89.8% of patients remained alive in GC and DC, respectively (P = 0.88). CONCLUSIONS: DC and GC adjuvant chemotherapies for completely resected NSCLC were well tolerated and appear free of major QoL effects, and are therefore representing candidates for comparison with the standard VC regimen

A randomized phase II trial assessing in advanced non-small cell lung cancer patients with stable disease after two courses of cisplatin-gemcitabine an early modification of chemotherapy doublet with paclitaxel-gemcitabine versus continuation of cisplatin-gemcitabine chemotherapy (GFPC 03-01 Study).

International audienceBACKGROUND: There is no consensus on the optimal treatment for patients with advanced non-small cell lung cancer and stable disease after cisplatin-based chemotherapy. The objective of the trial was to evaluate a switch to a different dual-agent chemotherapy. METHODS: Patients with stage IV non-small cell lung cancer and stable disease after two cycles of cisplatin (P) and gemcitabine (G) (P day1 (d(1)): 75 mg/m(2), G: 1250 mg/m(2) d(1) and d(8) every 3 weeks) were randomized to receive either two further cycles of PG (arm A) or paclitaxel (100 mg/m(2) d(1), d(8), d(15)) plus gemcitabine (1250 mg/m(2) d(1) and d(8), every 4 weeks) (arm B). RESULTS: Two-hundred-twenty-eight patients were enrolled between October 2003 and August 2006. After two cycles of PG, 98 patients (43%) had stable disease; 87 were randomized: 45 to arm A and 42 to arm B. The objective response rates were 15.6% (6.5-29.4) and 21.4% (10.3-36.8) in arms A and B. Overall survival after randomization was 9.6 months (7.0-13.8) in arm A and 9.3 months (7.4-13.3) in arm B. Adverse events were similar in the two arms for hematological and non hematological toxicities. CONCLUSIONS: Sequential first-line chemotherapy in these patients is feasible with no difference in response rates. These results do not warrant a phase III trial

Estimation des risques de cancer au sein de la cohorte «Enfant Scanner»

National audienceObjectifs: Depuis plusieurs décennies, les actes diagnostiques utilisant les rayonnements ionisants (RI) se multiplient. De plus, la dose délivrée au cours des examens scanners est nettement plus élevée que celle délivrée en radiologie conventionnelle. Les enfants présentant une radiosensibilité accrue, il est important d’évaluer le risque de cancer après exposition au scanner pendant l’enfance. Dans ce contexte, l’IRSN a mis en place la cohorte « Enfant-Scanner » qui inclut les patients exposés à un scanner pour une pathologie non cancéreuse, avant l’âge de 10 ans, entre 2000 et 2011, dans les 21 CHU participants. Une première analyse, réalisée sur un échantillon de 67 000 enfants de la cohorte suivis jusqu’en 2011, a montré une augmentation de risque, non significative, de tumeur cérébrale et de leucémie associée à la dose cumulée. Cependant, le manque de puissance statistique de cette analyse, conséquence d’un nombre limité de cas de cancer et d’une courte durée de suivi, limitait la portée des résultats. De plus, cette analyse ne prenait que partiellement en compte les incertitudes dosimétriques.Matériel et méthode : Dans la présente analyse, 40 000 enfants supplémentaires ont été inclus et le suivi moyen a été prolongé de 5 ans. Les cancers incidents ont été identifiés jusqu’en 2016, à partir du Registre National des Cancers de l’Enfant (RNCE). Trois des cancers les plus fréquents chez l’enfant ont été étudiés : les tumeurs du système nerveux central (SNC), les leucémies et les lymphomes. Des facteurs de prédisposition au cancer (FP), comme des maladies génétiques ou des déficiences immunitaires, ont été collectés dans la base du Système National des Données de Santé (SNDS). Le SNDS a également permis d’identifier pour chaque patient les examens radiologiques reçus en dehors des CHU participants et après la période d’inclusion initiale. Des doses individuelles de RI ont été estimées à partir des protocoles utilisés dans les CHU. L’effet de l’exposition aux RI sur les risques instantanés de survenue de cancers a été estimé avec des modèles de Cox. A partir des données du PACS (Picture Archiving and Communication System) collectées dans 8 CHU et en proposant un modèle hiérarchique bayésien, une évaluation de l’impact des différentes sources d’incertitudes dosimétriques sur les estimations de risques est en cours de réalisation. Résultats : Les doses moyennes cumulées au cerveau et à la moelle osseuse étaient respectivement de 28 et 10 milliGray (mGy). Environ 73% des enfants ont été exposés à un seul examen scanner. Soixante-quinze tumeurs du SNC, 39 leucémies et 41 lymphomes ont été diagnostiqués après une période d’exclusion de 2 ans. Trois pour cent des enfants de la cohorte présentaient des FP. Chez les enfants sans FP, des associations significatives entre le risque de tumeur cérébrale et la dose absorbée au cerveau d’une part (HR [IC 95%] : 1,05 [1,01 ; 1,09] pour une augmentation de 10 mGy de la dose) et le risque de leucémie et la dose absorbée à la moelle osseuse d’autre part (HR [IC 95%] : 1,17 [1,09 ; 1,26] pour une augmentation de 10 mGy de la dose) ont été observées. Pour les lymphomes, aucune augmentation de risque n’a été mise en évidence en fonction de la dose. De même, aucune association entre le risque de cancer et la dose reçue n’a été observée chez les enfants présentant un FP. L’impact de la prise en compte des nouveaux examens et des incertitudes de doses sur l’analyse dose réponse sera présentée lors du congrès.Conclusion : La mise-à-jour de la cohorte Enfant-Scanner, en augmentant la puissance statistique de l’analyse, a permis de mettre en évidence des associations significatives entre la dose de RI à l’organe et le risque de tumeurs du SNC et de leucémie chez les patients sans FP. L’absence d’augmentation de risque chez les patients présentant un FP peut s’expliquer en partie par le faible effectif de cette population

Childhood cancer risks estimates following CT scans: an update of the French CT cohort study

International audienceObjectives: Increased risks of central nervous system (CNS) tumors and leukemia associated with computed tomography (CT)exposure during childhood have been reported in recent epidemiological studies. However, no evidence of increased risks wassuggested in a previous analysis of the French CT cohort. This study benefits from an updated cohort with a longer follow-up anda larger sample size of patients.Methods: The patients were followed from the date of their first CT (between 2000 and 2011) until their date of cohort exitdefined as the earliest among the following: 31 December 2016, date of death, date of first cancer diagnosis or date of their 18thbirthday. Cancer incidence, vital status, cancer predisposing factors (PFs), and additional CT scans were collected via externalnational databases. Hazard ratios (HRs) associated to cumulative organ doses and sex were estimated from Cox models.Results: At the end of follow-up, mean cumulative doses were 27.7 and 10.3 mGy for the brain and the red bone marrow (RBM),respectively. In patients without PFs, an HR per 10 mGy of 1.05 (95% CI: 1.01–1.09) for CNS tumors, 1.17 (95% CI: 1.09–1.26)for leukemia, and 0.96 (95% CI: 0.63–1.45) for lymphoma was estimated. These estimates were not modified by the inclusion ofCT scans performed outside the participating hospitals or after the inclusion period.Conclusions: This study shows statistically significant dose-response relationships for CNS tumors and leukemia for patientswithout PFs

Childhood CT scans and cancer risks estimates: an update of the French CT cohort study

International audienceBackground: Computed tomography (CT) has been used increasingly worldwide over the last decades. However, concerns have been raised about potentially radiation-related cancer risks, particularly after exposure to CT in childhood, due to the greater radiation sensitivity of children and to their longer life expectancy allowing to develop radiation associated late health effects. Increased risks of central nervous system (CNS) tumours and leukaemia associated with CT exposure during childhood have been reported in recent epidemiological studies. However, no evidence of significant increased risks was suggested in a previous analysis of almost 60,000 patients of the French CT cohort.Methods: The French CT cohort includes patients born after 1994 who received at least one CT scan before the age of 10 years between 2000 and 2011 and had no cancer diagnosis before the first CT. Examinations and radiological protocols carried out between 2000 and 2011 in the 21 participating hospitals were retrieved to estimate cumulative absorbed doses to the brain and the red bone marrow (RBM). In this work, the cohort was updated in order to extend the follow-up (5 additional years) and to increase the sample size of patients (40,000 new patients with reported vital status). Moreover, the cohort was linked with the National Health Data System (Système national des données de santé, SNDS) to collect CTs performed outside the participating hospitals or after the inclusion period. Hazard ratios (HRs) associated to cumulative organ doses and gender were estimated from Cox models. To rule out the possibility of reverse causation, an exclusion period of 2 years was applied. A latency period was also applied to consider the minimal latency period expected between the exposure and the studied outcome. To address the potential issue of bias by indication, the models were fitted to the restricted sub-cohorts of patients with and without cancer predisposing factors (PFs) separately.Results: The updated French CT cohort includes 103,015 patients followed for 9.3 years in average. 3.1% of patients had PFs. Considering only the CTs performed in the participating hospitals until 2011, mean cumulative doses were 24.5 and 9.3 mGy for the brain and the RBM respectively. Adding the CTs performed outside the participating hospitals or after the inclusion period increased the mean cumulative doses to 27.7 mGy and 10.3 mGy for the brain and the RBM respectively. This study showed statistically significant dose-response relationships for CNS tumours (HR per 10 mGy: 1.05, 95% CI: 1.01 – 1.09) and leukaemia (HR per 10 mGy: 1.17, 95% CI: 1.09 – 1.26) for patients without PFs. No evidence of association was observed for lymphoma for these patients and for the three types of cancer for the patients with PFs. Inclusion of additional CTs registered in the SNDS did not impact the HR estimates.Conclusions: Estimates were compatible with the ones obtained in the previous analysis of the French CT cohort. However, the extended follow-up and the larger sample size of the cohort increased the statistical power, leading to statistically significant dose-response relationships for CNS tumours and leukaemia for patients without PFs