Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

Efficacy of endoscopic gastrojejunal bypass in obese Yucatan pigs: a comparative animal study

Abstract Background Natural orifice transluminal endoscopy surgery (NOTES) gastrojejunal anastomosis (GJA) with duodenal exclusion (DE) could be used as a less invasive alternative to surgical gastric bypass. The aim of this study was to compare the efficacy and safety of both methods for bariatric purpose. Methods This was a prospective, experimental and comparative study on 27 obese living pigs, comparing 4 groups: GJA alone (group 1, G1), GJA + DE (group 2, G2), surgical gastric bypass (group 3, G3), control group (group 4, G4). GJA was endoscopically performed, using NOTES technic and LAMS, while DE was performed surgically for limb length selection. Animals were followed for 3 months. Primary outcome included technical success and weight change, while secondary endpoints included the rate of perioperative mortality and morbidity, histological anastomosis analysis and biological analysis. Results Technical success was 100% in each intervention group. No death related to endoscopic procedures occurred in the endoscopic groups, while early mortality (< 1 month) was 57,1% in the surgical group, all due to anastomotic dehiscence. At 3 months, compared to baseline, mean weight change was + 3,1% in G1 (p = 0,46); -14,9% in G2 (p = 0,17); +5,6% in G3 (p = 0,38) and + 25% in G4 (p = 0,029). Histopathological analysis of endoscopic GJA showed complete fusion of different layers without leak or abscess. Conclusions Endoscopic GJA with DE provides the efficacy of bypass on weight control in an animal model. Next steps consist of the development of devices to perform exclusively endoscopically limb length selection and DE

Implementation of a surgical simulation care pathway approach to training in emergency abdominal surgery

Background Simulation-based care pathway approach (CPA) training is a novel approach in surgical education. The objective of the present study was to determine whether CPA was feasible for training surgical residents and could improve efficiency in patients’ management. A common disease was chosen: acute appendicitis. Methods All five junior residents of our department were trained in CPA: preoperative CPA consisted in virtual patients (VPs) presenting with acute right iliac fossa pain; intraoperative CPA involved a virtual competency-based curriculum for laparoscopic appendectomy (LAPP); finally, post-operative VP were reviewed after LAPP. Thirty-eight patients undergoing appendectomy were prospectively included before (n = 21) and after (n = 17) the training. All demographic and perioperative data were prospectively collected from their medical records, and time taken from admission to management was measured. Results All residents had performed less than 10 LAPP as primary operator. Pre- and intraoperative data were comparable between pretraining and post-training patients. Times to liquid and solid diet were significantly reduced after training [7 h (2–20) vs. 4 (4–6); P = 0.004, and 17 h (4–48) vs. 6 (4–24); P = 0.005] without changing post-operative morbidity [4 (19%) vs. 0 (0); P = 0.11] and length of stay [48 h (30–264) vs. 44 (21–145); P = 0.22]. Conclusions CPA training is feasible in abdominal surgery. In the current study, it improved patients’ management in terms of earlier oral intake

Value of early repeated abdominal CT in selective non-operative management for blunt bowel and mesenteric injury

International audienceObjectivesTo evaluate the performance of an early repeated computed tomography (rCT) in initially non-operated patients with blunt bowel and mesenteric injuries (BBMI).MethodsThis was a monocentric retrospective observational study from 2009 to 2017 of patients with a BBMI on initial CT (iCT). Patients initially non-operated on were scheduled for a rCT within 48 h. Initial CT and rCT diagnostic performance were compared based on a surgical injury prediction score previously described. For statistical analysis, we used the chi-square analyses for paired data (McNemar test).ResultsEighty-four patients (1.9% of trauma) had suspected BBMI on iCT. Among these patients, 22 (26.2%) were initially operated on, 18 (21.4%) were later operated on, and 44 (52.4%) were not operated on. The therapeutic laparotomy rate was 85%. Thirty-four patients initially non-operated on had a rCT. The absolute value of the CT scan score increased for 15 patients (44.1%). The early rCT diagnostic performance, compared with iCT, showed an increase in sensitivity (from 63.6 to 91.7%), in negative predictive value (from 77.4 to 94.7%), and in AUC (from 0.77 to 0.94).ConclusionIn initially non-operated patients with BBMI lesions, the performance of an early rCT improved the sensitivity of lesion detection requiring surgical repair and the security of patient selection for non-operative treatment

Value of early repeated abdominal CT in selective non-operative management for blunt bowel and mesenteric injury

International audienc

Colorectal surgery and enhanced recovery: Impact of a simulation-based care pathway training curriculum

BACKGROUND: The aim was to determine whether a simulation-based care pathway approach (CPA) curriculum could improve compliance for enhanced recovery programs (ERP), and residents' participation in laparoscopic colorectal surgery (LCS). Indeed, trainee surgeons have limited access to LCS as primary operator, and ERP have improved patients' outcomes in colorectal surgery (CS). METHODS: All residents of our department were trained in a simulation-based CPA: perioperative training consisted in virtual patients built according to guidelines in both ERP and CS, whilst intraoperative training involved a virtual reality simulator curriculum. Twenty consecutive patients undergoing CS were prospectively included before (n=10) and after (n=10) the training. All demographic and perioperative data were prospectively collected, including compliance for ERP. Residents' participation as primary operator in LCS was measured. RESULTS: Five residents (PGY 4-7) were enrolled. None had performed LCS as primary operator. Overall satisfaction and usefulness were both rated 4.5/5, usefulness of pre-, post- and intraoperative training was rated 5/5, 4.5/5 and 4/5, respectively. Residents' participation in LCS significantly improved after the training (0% (0-100) vs. 82.5% (10-100); P=0.006). Pre- and intraoperative data were comparable between groups. Postoperative morbidity was also comparable. Compliance for ERP improved at Day 2 in post-training patients (3 (30%) vs. 8 (80%); P=0.035). Length of stay was not modified. CONCLUSIONS: A simulated CPA curriculum to training in LCS and ERP was correctly implemented. It seemed to improve compliance for ERP, and promoted residents participation as primary operator without adversely altering patients' outcomes