Bevacizumab plus neoadjuvant chemotherapy in patients with HER2-negative inflammatory breast cancer (BEVERLY-1): a multicentre, single-arm, phase 2 study.

BACKGROUND: Addition of bevacizumab to standard chemotherapy in the neoadjuvant setting in patients with HER2-negative metastatic breast cancer improves progression-free survival and the proportion of patients achieving pathological complete response. In the BEVERLY-1 (UCBG-0802) trial we aimed to assess the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy in the treatment of patients with HER2-negative inflammatory breast cancer. METHODS: We did this phase 2, single-arm trial at 20 hospitals in France. We enrolled women aged 18 years or older who had non-metastatic HER2-negative inflammatory breast cancer. Patients underwent 3-week treatment cycles, receiving neoadjuvant intravenous fluorouracil (500 mg/m(2)), epirubicin (100 mg/m(2)), cyclophosphamide (500 mg/m(2)), and bevacizumab (15 mg/kg) during cycles 1-4, then docetaxel (100 mg/m(2)) and bevacizumab during cycles 5-8. 2-4 weeks after surgery, patients received adjuvant radiotherapy, hormone therapy (if they had a hormone receptor-positive tumour), and adjuvant intravenous bevacizumab. The primary endpoint was pathological complete response in breast and axillary lymph nodes after neoadjuvant treatment, determined after centralised review in accordance with Sataloff classification and assessed in the intention-to-treat population. Our analysis of toxic effects included all patients who received at least one dose of bevacizumab. The trial is complete and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT00820547. FINDINGS: Between Jan 16, 2009, and Sept 8, 2010, we enrolled 101 patients, one of whom withdrew consent before treatment, leaving 100 patients in the primary endpoint analysis. After neoadjuvant therapy, 19 (19% [95% CI 12-28]; p=0·16) of 100 patients achieved a pathological complete response according to centralised review. The most frequent grade 3-4 events during the neoadjuvant phase were neutropenia (89 [89%] of 100 patients), febrile neutropenia (37 [37%]), and mucositis (23 [23%]) and during the adjuvant phase the most frequent grade 3-4 adverse event was proteinuria (5 [7%] of 75 patients). One (1%) patient died of thrombotic microangiopathy after cycle 1, which was thought to be related to bevacizumab. Two patients (3%) developed transitory heart failure. 48 (48%) patients had serious adverse events, the most frequent of which was febrile neutropenia (28 [28%]). INTERPRETATION: Our results suggest that the addition of bevacizumab to neoadjuvant and adjuvant chemotherapy does not provide clinical benefit to patients with non-metastatic HER2-negative inflammatory breast cancer. Longer follow-up and correlative studies to identify patients who might benefit from bevacizumab are needed. FUNDING: Roche, La Ligue Nationale contre le Cancer, UNICANCER, and Chugai Pharma.

Weekly paclitaxel, capecitabine, and bevacizumab with maintenance capecitabine and bevacizumab as first-line therapy for triple-negative, metastatic, or locally advanced breast cancer: Results from the GINECO A-TaXel phase 2 study.

BACKGROUND: The current study was performed to determine the efficacy and safety of first-line combination therapy with bevacizumab, paclitaxel, and capecitabine for triple-negative, locally advanced/metastatic breast cancer (LA/MBC). METHODS: Patients with measurable triple-negative LA/MBC who had received no prior chemotherapy for their disease received 4-weekly cycles of paclitaxel (80 mg/m2 on days 1, 8, and 15 for up to 6 cycles) combined with capecitabine (800 mg/m2 twice daily on days 1-5, 8-12, and 15-19) and bevacizumab (10 mg/kg on days 1 and 14) repeated every 4 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was the objective response rate; secondary endpoints were progression-free survival, duration of response, overall survival, and safety. RESULTS: Between April 2010 and March 2012, 62 eligible patients were enrolled. The median age of the patients was 57 years, 74% had received adjuvant chemotherapy, and 65% had visceral metastases. Patients received a median of 6 cycles (range, 1-45 cycles). The objective response rate was 77% (95% confidence interval [95% CI] 66%-88%), including complete response in 19% of patients. The median duration of response was 5.6 months (range, 1.3-27.6 months). The median progression-free survival was 7.6 months (95% CI, 6.3-9.0 months) and the median overall survival was 19.2 months (95% CI, 17.4-20.9 months). The most common grade ≥3 adverse events were hypertension (35% of patients) and neutropenia (23% of patients); 5% of patients experienced febrile neutropenia. Grade ≥2 hand-foot syndrome, alopecia, and nail toxicity each occurred in 40% of patients (adverse events were recorded before every cycle and graded according to Common Terminology Criteria for Adverse Events [version 4.0]). Treatment was interrupted because of toxicity in 22% of patients. CONCLUSIONS: A triplet regimen of paclitaxel, capecitabine, and bevacizumab followed by maintenance therapy with capecitabine and bevacizumab demonstrated high activity and manageable safety in this difficult-to-treat population. Cancer 2016;122:3119-26. © 2016 American Cancer Society.

Prognostic stratification ability of the CPS+EG scoring system in HER2-low and HER2-zero early breast cancer treated with neoadjuvant chemotherapy.

BACKGROUND: The CPS+EG scoring system was initially described in unselected early breast cancer (eBC) patients treated with neoadjuvant chemotherapy (NAC), leading to refined prognostic stratification, and thus helping to select patients for additional post-NAC treatments. It remains unknown whether the performance is the same in new biological breast cancer entities such as the HER2-low subtype. PATIENTS AND METHODS: Outcomes (disease-free (DFS) and overall survival OS)) of 608 patients with HER2-non amplified eBC and treated with NAC were retrospectively analyzed according to CPS-EG score. We compared the prognostic stratification abilities of the CPS+EG in HER2-low and HER2-0 eBC, analyzing ER+ and ER- tumors separately. RESULTS: In ER+ eBC, the CPS+EG scoring system seems to retain a prognostic value, both in HER2-low and HER2-0 tumors, by distinguishing populations with significantly different outcomes (good: score 0-1, poor: score 2-3, and very poor: score 4-5). Using C-indices for DFS and OS, CPS+EG provided the highest prognostic information in ER+ eBC, especially in HER2-0 tumors. In contrast, in ER- eBC, the CPS+EG does not appear to be able to distinguish different outcome groups, either in HER2-low or HER2-0 tumors. In ER- eBC, C-indices for DFS and OS were highest for pathological stage, reflecting the predominant prognostic importance of residual disease in this subtype. CONCLUSIONS: HER2-low status does not influence the prognostic performance of the CPS+EG score. Our results confirm the usefulness of the CPS+EG score in stratifying the prognosis of ER+ eBC after NAC, for both HER2-0 and HER2-low tumors. For ER- eBC, HER2-low status does not influence the performance of the CPS+EG score, which was lower than that of the pathological stage alone.

Patient Preference Between Cabazitaxel and Docetaxel for First-line Chemotherapy in Metastatic Castration-resistant Prostate Cancer: The CABADOC Trial.

BACKGROUND: The taxanes docetaxel and cabazitaxel prolong overall survival for men with metastatic castration-resistant prostate cancer (mCRPC), with cabazitaxel approved in the postdocetaxel setting only. Recent data suggest they have similar efficacy but a different safety profile in the first-line mCRPC setting. OBJECTIVE: To assess patient preference between docetaxel and cabazitaxel among men who received one or more doses of each taxane and did not experience progression after the first taxane. DESIGN, SETTING, AND PARTICIPANTS: Chemotherapy-naïve patients with mCRPC were randomized 1:1 to receive docetaxel (75 mg/m2 every 3 wk × 4 cycles) followed by cabazitaxel (25 mg/m2 every 3 wk × 4 cycles) or the reverse sequence. Randomization was stratified by prior abiraterone or enzalutamide use. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was patient preference, assessed via a dedicated questionnaire after the second taxane. Secondary endpoints included reasons for patient preference, prostate-specific antigen response, radiological progression-free survival, and overall survival. This clinical trial is registered at ClinicalTrials.gov as NCT02044354. RESULTS AND LIMITATIONS: Of 195 men randomized, 152 met the prespecified modified intent-to-treat criteria for analysis. Overall, 66 patients (43%) preferred cabazitaxel, 40 (27%) preferred docetaxel, and 46 (30%) had no preference (p = 0.004, adjusted for treatment period effect). More patients preferred treatment period 1 (43%, 95% confidence interval [CI] 36-52%) versus period 2 (27%, 95% CI 20-34%). Patient preference for cabazitaxel was mainly related to less fatigue (72%), better quality of life (64%), and other adverse events (hair loss, pain, nail disorders, edema). Adverse events were consistent with the known safety profile of each drug. CONCLUSIONS: A significantly higher proportion of chemotherapy-naïve men with mCRPC who received both taxanes preferred cabazitaxel over docetaxel. Less fatigue and better quality of life were the two main reasons driving patient choice. PATIENT SUMMARY: Men with metastatic castration-resistant prostate cancer preferred cabazitaxel over docetaxel for chemotherapy, mainly because of less fatigue and better quality of life.

Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin With or Without Panitumumab in Patients With Advanced Urothelial Carcinoma: Multicenter, Randomized, French Unicancer GETUG/AFU 19 Study.

This study looked at whether epidermal growth factor receptor inhibition by the monoclonal antibody panitumumab could increase the efficacy of standard chemotherapy in advanced urothelial cancer. Results were disappointing, with higher toxicity and no improvement in efficacy in the combination arm. BACKGROUND: Epidermal growth factor receptor (EGFR) overexpression is frequent and associated with poor outcome in urothelial carcinoma. EGFR inhibition could improve the antitumor activity of chemotherapy. PATIENTS AND METHODS: Patients with advanced, treatment-naïve, histologically confirmed advanced urothelial carcinoma and no HRAS or KRAS mutation in the primary tumor received dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) without or with the anti-EGFR monoclonal antibody panitumumab (Pmab). A randomized (1:2) phase II design was used with progression-free survival (PFS) as the primary endpoint. RESULTS: Ninety-seven eligible patients were randomized; 96 patients were evaluable for toxicity and 87 for efficacy. The median PFS were 6.8 months (95% confidence interval [CI], 6.3-9.2) for dd-MVAC and 5.7 months (95% CI, 4.6-6.4 months) for dd-MVAC+Pmab. For both immunohistochemical and molecular definition of basal/squamous-like (BASQ) tumors, no difference was observed in objective response rates or PFS between the two arms in BASQ and non-BASQ tumors. CONCLUSION: dd-MVAC+Pmab was associated with more serious adverse events and no improvement in efficacy outcomes.

Prospective comparison of whole-body MRI with diffusion-weighted and conventional imaging for the follow-up of neuroendocrine tumors.

AIM: To determine whether whole-body magnetic resonance imaging is valuable in staging of neuroendocrine tumors by comparison with the conventional imaging defined by the combination of computed tomography and somatostatin receptor scintigraphy. METHODS: This study concerned the patients included in the multicenter prospective study NCT02786303 with the following inclusion criteria: well-differentiated gastroenteropancreatic neuroendocrine tumors or of unknown primary, and computed tomography, whole-body magnetic resonance imaging and somatostatin receptor scintigraphy performed within 6 weeks. Results of the conventional imaging were compared with those of magnetic resonance imaging. Discrepancies between the conventional imaging and magnetic resonance imaging were evaluated by reviewing medical records. RESULTS: Thirty-one patients (17 men and 14 women) were prospectively included. Complete concordance between the magnetic resonance imaging and the conventional imaging results was observed in 25 patients and discrepancies in 6. Whole-body magnetic resonance imaging detected more liver lesions than the conventional imaging did but standard imaging set was more effective in the detection of bone and peritoneum lesions than magnetic resonance imaging. Detecting more lesions had no impact on therapeutic management. CONCLUSIONS: Whole-body magnetic resonance imaging including diffusion weighted may be a valuable alternative to computed tomography and somatostatin receptor scintigraphy. Further studies should compare whole-body MRI to the 68Ga PET/CT.

Docetaxel first-line therapy in HER2-negative advanced breast cancer: a cohort study in patients with prospectively determined HER2 status.

Docetaxel is one of the most active cytotoxic drugs against breast cancer, but data are lacking on specific activity in molecularly selected subgroups. This retrospective study was aimed at assessing the outcome and prognostic factors for survival of patients with HER2-negative tumors receiving first-line docetaxel-based chemotherapy for advanced breast cancer (ABC). The medical charts of all 162 patients with prospectively proven HER2-negative ABC and having received docetaxel as first-line chemotherapy for metastatic disease at our institution were retrospectively reviewed with special emphasis on docetaxel efficacy. Potential prognostic factors were sought using multivariate analysis. Median progression-free survival (PFS) was 12 months (95% confidence interval 9.7-14.8) and median overall survival (OS) was 34.9 months (95% confidence interval 28.1-52.1). Hormone receptor (HR) status was the strongest prognostic factor in the univariate analysis for both PFS [hazard ratio = 0.23; P = 0.00000063] and OS (hazard ratio = 0.35; P = 0.0000079). After multivariate analysis, only three independent variables for PFS (HR-positive tumor, no prior adjuvant/neoadjuvant chemotherapy, and isolated bone metastases) and two for OS (HR-positive tumor and isolated bone metastases) remained predictive of a favorable outcome. HER2-negative, HR-positive ABC patients have a relatively good prognostic after docetaxel-containing first-line therapy. The subset of HER2-negative, HR-negative (triple-negative) has a very poor outcome, and innovative therapies are eagerly awaited for these patients.

[Primary mediastinal germs cells tumors: a twenty years experience in a comprehensive cancer center]. / Tumeurs germinales primitives du médiastin : expérience de l'Institut de cancérologie de Lorraine sur une période de 20 ans (1990-2012).

UNLABELLED: The aim of this study is to report treatments results of patients with primary germ cell tumors (GCTs) of mediastinum. METHODS: A retrospective review was done of 19 consecutive patients with mediastinal GCTs treated in "Institut de cancérologie de Lorraine" between 1990 and 2012. RESULTS: A total of 19 patients were enrolled in this study. Three patients had pure seminoma and 16 patients had non-seminomatous germ cell tumors. All patients were treated with cisplatinum based chemotherapy at a dose of 33.48 mg/m(2)/week. At the end of chemotherapy, three patients (15.8%) had complete response and negative marker, seven of them (36.8%) had partial response and negative marker, five of them (26.32%) had partial response and positive marker, three of them (15.8%) had progressive disease (refractory disease) and one patient died because of the disease during treatment. The 1-year and 5-year overall survival rates were respectively 78 and 36% and the progression-free survival rate was 43%. When relapse occurred, this happened within a 13 month period. CONCLUSION: Our study confirmed the good management of mediastinal GCTs in our institute with similar results compared to literature.

Health-related quality-of-life assessment in gastrointestinal cancer: are results relevant for clinical practice?

PURPOSE OF REVIEW: Health-related quality-of-life studies are now recognized as critical to understand the burden of disease and treatments on patients' well being. Significant advances have been recently achieved in gastrointestinal cancers, including the development and clinical use of new robust quality-of-life instruments. We review recent literature to evaluate whether quality-of-life assessment contributes to optimal patient information and helps treatment choices. RECENT FINDINGS: Treatments of gastrointestinal cancers have changed in the last few years with increasing use of multimodal therapies and advances in surgical techniques, especially for low-lying rectal cancers. Concurrent to the development of sphincter-saving procedures, however, the long-term consequences of a permanent stoma on quality of life have been debated. Results of new palliative treatments should also be considered looking at preservation or improvement of quality of life and not only prolongation of life. SUMMARY: Gastrointestinal malignancies impact strongly on patient quality of life due to the aggressiveness of the treatments. Short-term negative effects of surgery and specific deficits in survivors were recently described in gastrointestinal cancers. Baseline quality-of-life data predict length of survival in hepatocarcinoma and metastatic colorectal cancer. Generally, quality-of-life results help to fully inform the patients of the advantages or disadvantages of therapeutic options, including adjuvant and palliative treatments.