Long-term survival in patients with recurrent glioblastoma treated with bevacizumab: a multicentric retrospective study.

PURPOSE: Recurrence of glioblastoma (GB) occurs in most patients after standard concomitant temozolomide-based radiochemotherapy (CTRC). Bevacizumab (BV), an anti-VEGF antibody, has an effect on progression-free survival (PFS) but not on overall survival (OS). However, a small part of the patients experience a survival, longer than expected. This retrospective study aims to characterize long responder (LR) patients treated with BV for a first or second GBM recurrence. METHODS: Medical records from patients (814) who received BV for a first or second recurrence of primary glioblastoma between September 2010 and September 2015, and initially treated by CTRC were analyzed. Patients, who had at least a stable disease according to RANO criteria at 12 months from the start of BV, were included. Patients who had, a secondary GB, or received BV in neoadjuvant or adjuvant setting were excluded. RESULTS: We focused on 65 LR patients without progression 12 months after the first injection of BV (8%). Median PFS was 21.7 months [95% CI (19.3; 27.2)] and median OS was 31.1 months [95% CI (24.3; 37.5)] from the start of BV. No prognostic factor was associated with OS in multivariate analysis. Karnofsky performance status, neurological status and corticosteroid dose were stable at 12 months. CONCLUSIONS: Our results highlight that among patients receiving bevacizumab in first or second recurrence, one patient out of twelve could be classified as LR. A median OS of 31.1 months from the start of BV could be expected in this subpopulation. These findings reinforce the potential benefit of the use of BV in the situation of recurrence. 256 words.

Predictive factors of pathologic complete response of HER2-positive breast cancer after preoperative chemotherapy with trastuzumab: development of a specific predictor and study of its utilities using decision curve analysis.

PURPOSE: The aim of this study was to assess the Institut Gustave Roussy/M.D. Anderson Cancer Center (IGR/MDACC) nomogram in predicting pathologic complete response (pCR) to preoperative chemotherapy in a cohort of human epidermal growth factor receptor 2 (HER2)-positive tumors treated with preoperative chemotherapy with trastuzumab. We then combine clinical and pathological variables associated with pCR into a new nomogram specific to HER2-positive tumors treated by preoperative chemotherapy with trastuzumab. PATIENTS AND METHODS: Data from 270 patients with HER2-positive tumors treated with preoperative chemotherapy with trastuzumab at the Institut Curie and at the Georges François Leclerc Cancer Center were used to assess the IGR/MDACC nomogram and to subsequently develop a new nomogram for pCR based on multivariate logistic regression. Model performance was quantified in terms of calibration and discrimination. We studied the utility of the new nomogram using decision curve analysis. RESULTS: The IGR/MDACC nomogram was not accurate for the prediction of pCR in HER2-positive tumors treated by preoperative chemotherapy with trastuzumab, with poor discrimination (AUC = 0.54, 95% CI 0.51-0.58) and poor calibration (p = 0.01). After uni- and multivariate analysis, a new pCR nomogram was built based on T stage (TNM), hormone receptor status, and Ki67 (%). The model had good discrimination with an area under the curve (AUC) at 0.74 (95% CI 0.70-0.79) and adequate calibration (p = 0.93). By decision curve analysis, the model was shown to be relevant between thresholds of 0.3 and 0.7. CONCLUSION: To the best of our knowledge, ours is the first nomogram to predict pCR in HER2-positive tumors treated by preoperative chemotherapy with trastuzumab. To ensure generalizability, this model needs to be externally validated.

Paclitaxel plus bevacizumab or paclitaxel as first-line treatment for HER2-negative metastatic breast cancer in a multicenter national observational study.

BACKGROUND: Bevacizumab combined with paclitaxel as first-line chemotherapy for patients with HER2-negative metastatic breast cancer (MBC) has led to mixed results in randomized trials, with an improvement in progression-free survival (PFS) but no statistically significant overall survival (OS) benefit. Real-life data could help in assessing the value of this combination. PATIENTS AND METHODS: This study aimed to describe the outcome following first-line paclitaxel with or without bevacizumab in the French Epidemiological Strategy and Medical Economics (ESME) database of MBC patients, established in 2014 by Unicancer. The primary and secondary end points were OS and PFS, respectively. RESULTS: From 2008 to 2013, 14 014 MBC patient files were identified, including 10 605 patients with a HER2-negative status. Of these, 3426 received paclitaxel and bevacizumab (2127) or paclitaxel (1299) as first-line chemotherapy. OS adjusted for major prognostic factors was significantly longer in the paclitaxel and bevacizumab group compared with paclitaxel [hazard ratio (HR) 0.672, 95% confidence interval (CI) 0.601-0.752; median survival time 27.7 versus 19.8 months]. Results were consistent in all supportive analyses (using a propensity score for adjustment and as a matching factor for nested case-control analyses) and sensitivity analyses. Similar results were observed for the adjusted PFS, favoring the combination (HR 0.739, 95% CI 0.672-0.813; 8.1 versus 6.4 months). CONCLUSIONS: In this large-scale, real-life setting, patients with HER2-negative MBC who received paclitaxel plus bevacizumab as first-line chemotherapy had a significantly better OS and PFS than those receiving paclitaxel. Despite robust methodology, real-life data are exposed to important potential biases, and therefore, results need to be treated with caution. Our data cannot therefore support extension of current use of bevacizumab in MBC.

[Non-metastatic triple-negative breast cancer in 2016: Definitions and management]. / Tumeurs localisées du sein triple négatives en 2016 : définitions et prise en charge.

Triple-negative breast cancer (TN), as defined by the triple negativity in immunohistochemistry: the absence of estrogen receptor, progesterone receptor and the absence of overexpression or amplification of HER2, corresponds to 15 % of invasive breast cancers. This is a very heterogeneous group of tumors both at the genomic and transcriptomic level and at morphological, clinical and prognostic level. Although there are some good prognosis forms, the majority of TN tumors is characterized by a poor prognosis with a greater frequency of visceral metastases and a maximum risk of relapse in the first two years after diagnosis. Systemic adjuvant treatment with chemotherapy is almost always indicated. The surgical treatment and radiotherapy treatment should be comparable to the other subtypes and obey the same rules of oncologic surgery. TN tumors are not associated with a higher risk of locoregional relapse after conservative treatment and adjuvant radiotherapy. Optimization of systemic therapies is currently and for the last decade a challenge. A number of targeted therapies and efficiency biomarkers identification of these targeted therapies is essential to allow significant progress in optimizing systemic therapy for these tumors.

[Preoperative treatments of rectal cancers]. / Traitements préopératoires des cancers rectaux.

Surgery alone is no longer appropriate to the treatment of T3-T4 resecable rectal cancer. Preoperative chemoradiotherapy has recently been approved as the new standard treatment. This approach improves local control with local failure rate raranging now around 6-8%. However, it does not impact on overall survival. It becomes urgent to develop new concepts and a basic research in the understanding of the biological mechanisms that may explain the resistance of the micrometastatic process.