BMJ Open

PURPOSE: The currently ongoing Epidemiological Strategy and Medical Economics (ESME) research programme aims at centralising real-life data on oncology care for epidemiological research purposes. We draw on results from the metastatic breast cancer (MBC) cohort to illustrate the methodology used for data collection in the ESME research programme. PARTICIPANTS: All consecutive >/=18 years patients with MBC treatment initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres were selected. Diagnostic, therapeutic and follow-up data (demographics, primary tumour, metastatic disease, treatment patterns and vital status) were collected through the course of the disease. Data collection is updated annually. FINDING TO DATE: With a recruitment target of 30 000 patients with MBC by 2019, we currently screened a total of 45 329 patients, and >16 700 patients with a metastatic disease treatment initiated after 2008 have been selected. 20.7% of patients had an hormone receptor (HR)-negative MBC, 73.7% had a HER2-negative MBC and 13.9% were classified as triple-negative BC (ie, HER2 and HR status both negative). Median follow-up duration from MBC diagnosis was 48.55 months for the whole cohort. FUTURE PLANS: These real-world data will help standardise the management of MBC and improve patient care. A dozen of ancillary research projects have been conducted and some of them are already accepted for publication or ready to be issued. The ESME research programme is expanding to ovarian cancer and advanced/metastatic lung cancer. Our ultimate goal is to achieve a continuous link to the data of the cohort to the French national Health Data System for centralising data on healthcare reimbursement (drugs, medical procedures), inpatient/outpatient stays and visits in primary/secondary care settings. TRIAL REGISTRATION NUMBER: NCT03275311; Pre-results

Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer

Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival. During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P=0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib). As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .)

Active breathing control combined with high dose 3D conformal radiotherapy for non small cell lung cancer patients with severe respiratory insufficiency: experience of the Centre Léon Bérard

International audienc

P14.127 From next generation sequencing and comparative genomic hybridization to personalised medicine for adult primary brain tumors: the profiler trial

Abstract BACKGROUND Personalized anti-tumoral therapies may currently be proposed on the basis of immuno-histochemistry, but also next-generation sequencing and comparative genomic hybridization. ProfiLER trial explored the feasibility, efficacy and the impact of molecular profiling for patients with solid or hematological advanced cancers including brain tumors. MATERIAL AND METHODS Patients with primary brain tumors, pre-treated with at least one line of anti-cancer treatment, could be included in this multicentric prospective trial. A molecular profile (next-generation sequencing and comparative genomic hydridization) was established on fresh or archived sample. Weekly molecular tumor board analysed results to propose as far as possible a molecular targeted therapy. RESULTS between February 2013 and December 2015, 141 patients with primary brain tumor were enrolled. One hundred five samples were further analyzed as 30 samples were excluded, and 6 are on-going. The rate of screen failure was 16/33 for stereotactic biopsy (49%) versus 11/104 (11%) for removal. The main representative histologic type of tumors were glioblastoma (n=46, 43,8%), low grade glioma (n=26, 24,8%), high grade glioma (n=12, 11,4%) and atypical and anaplastic meningioma (n=8, 7,6%). Median delay between the diagnostic of the primitive tumor and the inclusion in ProfiLER study was 2.7 years (0.2 - 29 years). Median delay between the consent and the results of the multidisciplinary meeting was 2.8 months (1–7.1 months). Forty-three patients (41%) presented at least one “druggable molecular alteration”. The most frequently altered genes were CDKN2A (n=18, 29%), EGFR (n=12, 20%), PDGFRa (n=8, 13%), PTEN (n=8, 13%), CDK4 (n=7, 11%), KIT (n=6, 10%), PIK3CA (n=5, 8%), MDM2 (n=3, 5%). Sixteen patients could not have a proposition of specific treatment due to death before MBT (n=5, 31.3%), lack of available clinical trials (n=9, 56%), or ambiguous results (n=2, 12.5%). Among the 27 patients (26%) for whom a specific therapy has been proposed, only six patients ultimately received a medical targeted therapy (everolimus n=3, erlotinib n=1, ruloxitinib n=1, sorafenib n=1). Four patients discontinued the treatment for toxicity, the 2 others for clinical progression. CONCLUSION routine high-throughput sequencing is feasible for brain tumors but delays should be reduced to be able to propose targeted therapies to patients fit enough to benefit from experimental treatment. Macroscopic surgery is the best way to obtain workable samples. Specific panel genes for neurologic tumors should be developed, as well as change of practices concerning exclusion criteria in clinical trials. </jats:sec