Prediction of survival with second-line therapy in biliary tract cancer: Actualisation of the AGEO CT2BIL cohort and European multicentre validations

BACKGROUND: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. METHODS: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. RESULTS: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). CONCLUSION: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design

What treatment in 2017 for inoperable pancreatic cancers?

Pancreatic adenocarcinoma is a frequent and severe disease, either diagnosed as metastatic pancreatic adenocarcinoma (MPA) or as locally advanced pancreatic carcinoma (LAPC). Though no improvement in patients outcome have been made between 1996 and 2011, since 5 years new treatment options have become available to treat our patients. New standard first line regimens, such as FOLFIRINOX and gemcitabine combined with nab-paclitaxel, have improved overall survivals and second line treatments have been tested and validated. Other first-line treatments have failed, but research remains active and trials are ongoing with promising new anti-cancer agents. These new effective regimens used for MPA have yielded promising results in LAPC patients in open cohorts or phase II trials and a recent trial have failed to demonstrate the added value of classical external radiotherapy in this setting. Here, we review current standards of care in LAPC and MPA, consider the latest challenges and strategic questions, and examine what we may hope for in the future.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Folfirinox versus gemcitabine/nab-paclitaxel as first-line therapy in patients with metastatic pancreatic cancer: a comparative propensity score study

International audienc

Fluropyrimidine single agent or doublet chemotherapy as second line treatment in advanced biliary tract cancer

International audienceFluoropyrimidine (FP) plus platinum chemotherapy has been recently established as a second-line (L2) preferred option in advanced biliary tract cancer (aBTC) (ABC-06 phase III trial). However, the overall survival (OS) benefit was limited and comparison with FP monotherapy was not available. Our aim was to assess the OS of patients treated with a FP monotherapy compared to a doublet with irinotecan or platinum in L2. We performed a retrospective analysis of two large multicenter prospective cohorts: a French cohort (28 centers) and an Italian cohort (9 centers). All consecutive patients with aBTC receiving FP-based L2 after gemcitabine plus cisplatin/gemcitabine plus oxaliplatin L1 between 2003 and 2016 were included. A subgroup analysis according to performance status (PS) and an exploratory analysis according to platinum sensitivity in L1 were planned. In the French cohort (n = 351), no significant OS difference was observed between the FP monotherapy and doublet groups (median OS: 5.6 vs 6.8 months, P = .65). Stratification on Eastern Cooperative Oncology Group (ECOG) PS showed similar results in PS 0-1 and 2. Median OS was not different between FP monotherapy, platinum- and irinotecan-based doublets (5.6 vs 7.1 vs 6.7 months, P = .68). Similar findings were observed in the Italian cohort (n = 174) and in the sensitivity analysis in pooled cohorts (n = 525). No L2 regimen seemed superior over others in the platinum resistant/refractory or sensitive subgroups. Our results suggest that FP monotherapy is as active as FP doublets in aBTC in L2, regardless of the patient PS and country, and could be a therapeutic option in this setting

Additional file 3: Figure S2. of Additive value of pre-operative and one-month post-operative lymphocyte count for death-risk stratification in patients with resectable pancreatic cancer: a multicentric study

Calibration plots at 48 months for the final multivariate model. Vertical axis is the observed proportion of patients surviving at time of interest. Grey line represents a perfectly calibrated model. Solid line is current prediction model performance with 95 % confidence intervals using bootstrap resampling procedure. (PDF 146 kb

Additional file 2: Table S1. of Additive value of pre-operative and one-month post-operative lymphocyte count for death-risk stratification in patients with resectable pancreatic cancer: a multicentric study

Separate multivariate cox-analysis. (PDF 290 kb

Additional file 1: Figure S1. of Additive value of pre-operative and one-month post-operative lymphocyte count for death-risk stratification in patients with resectable pancreatic cancer: a multicentric study

Overall survival according to cohort set. (PDF 85 kb