Sanofi Canada Research Articles

Trial in Progress: Feasibility and Validation Study of the LSC17 Score in Acute Myeloid Leukemia Patients

Trial in Progress: Feasibility and Validation Study of the LSC17 Score in Acute Myeloid Leukemia Patients

843P - The neutrophil-to-lymphocyte ratio (NLR) as a predictive marker of response to abiraterone acetate: A retrospective analysis of the COU302 study

Background: The neutrophil–lymphocyte ratio (NLR) is recognized as a prognostic marker in many cancers, including metastatic castration-resistant prostate cancer (mCRPC). In this study, we perform a retrospective analysis of the pivotal COU302 study of abiraterone acetate (AA) as first line therapy for men mCRPC. Methods: The COU302 study randomized men with minimally symptomatic mCRPC to 1000mg AA once daily plus 5mg prednisone (AA + P) twice daily or placebo plus 5mg prednisone (P) twice daily. We utilized Kaplan–Meier survival and cox proportional hazard analyses to assess the effect of baseline NLR on response to AA + P versus P. Adjustment co-variates were selected from a recently reported analysis of the PREVAIL study of enzalutamide in men with mCRPC. Based on this analysis, we selected a NLR cut-off value of 2.5. Outcomes assessed included the co-primary endpoints from the COU302 study overall survival (OS) , radiographic progression free-survival (RPFS) and PSA progression-free survival (PFS). Results: Among the 1088 patients in the COU302 study, baseline NLR values showed significant differences according to baseline albumin below median (3.16 vs 2.92, p = 0.011), but no other baseline covariates. Mean NLR significantly increased following treatment initiation and at the end of study compared to baseline. Among patients with a baseline NLR ≥2.5, there was similar OS in AA + P and P treatment arms (p = 0.26), which was confirmed on adjusted cox proportional hazards (AA +P HR 0.95, p = 0.65). AA + P showed a significant OS benefit versus P (p = 0.0011) in men with baseline NLR <2.5, with an adjusted HR of 0.723(p = 0.012). For RPFS, benefits for AA + P were seen in men with NLR <2.5 or ≥ 2.5, with the magnitude of benefit greater in men with NLR <2.5. In the AA + P arm, men with baseline NLR <2.5 had significantly better PSA PFS compared to baseline NLR ≥2.5 (p = 0.03); no significant differences were seen in men in the placebo arm. Conclusions: In the COU302 study, we observed that patients with a screening NLR<2.5 had a significant benefit to AA + P compared to P, whereas for patients with a screening NLR ≥2.5, this benefit was less evident. Increases in the NLR value from baseline could not be used to predict response to AA. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: V. Fradet: Speaker: Abbvie, Bayer, Ferring, Janssen, Sanofi; Consultant: Amgen, AstraZeneca, Astellas, Bayer, Ferring, Janssen, Sanofi; Adviser: Amgen, Astellas, Bayer, Ferring, Janssen, Sanofi; Research grant: Amgen, AstraZeneca, Astellas, Janssen, Sanofi; Clinical trial: AstraZeneca, Bayer, Janssen; Meeting sponsor: Bayer, Janssen, Lilly; Educational grant: Janssen. P. Toren: Scientific study or trial: Innocrin Pharma, Roche; Consultant, Advisor: Sanofi Canada, Ferring, Astellas, Abbvie. All other authors have declared no conflicts of interest.

ADEQUACY OF ANTICOAGULATION WITH ENOXAPARIN OR UNFRACTIONATED HEPARIN: THE CANADA PRIMARY PCI ANTICOAGULANT STREAM SUB-STUDY

ADEQUACY OF ANTICOAGULATION WITH ENOXAPARIN OR UNFRACTIONATED HEPARIN: THE CANADA PRIMARY PCI ANTICOAGULANT STREAM SUB-STUDY

Relocation as a catalyst for change: How leadership empowered employees and achieved organizational change at Sanofi Canada

This paper tells Sanofi’s relocation story and offers insight for organizations embarking on a similar journey. The work environment can be a powerful tool through which to communicate information about the organization and its values to both employees and the outside world. In 2013, the sale of part of its business prompted leading healthcare partner Sanofi Canada to relocate its headquarters. Moving from closed “silo” offices, to a state of the art open-plan work environment, Sanofi Canada achieved meaningful change in its work culture in a very short period of time: a companywide survey undertaken four months into life at their new headquarters revealed satisfied and engaged employees who were taking advantage of new technology and embracing new opportunities to collaborate. ©Journal of Professional Communication, all rights reserved.

Methylene blue treatment for cytokine release syndrome-associated vasoplegia following a renal transplant with rATG infusion: A case report and literature review.

Rabbit anti-thymocyte globulin (rATG) is an infusion of polyclonal rabbit-derived antibodies against human thymocyte markers, which can be used to prevent and treat acute rejection following organ transplantation. However, the product monograph issued by the manufacturer (Sanofi Canada) reports that serious immune-mediated reactions have been observed following the use of rATG, consisting of anaphylaxis or severe cytokine release syndrome (CRS), which is a form of vasoplegic syndrome (VS), in which distributive shock occurs refractory to norepinephrine (NE) and vasopressin (VP). Severe infusion-associated reactions are consistent with CRS and can cause serious cardiac or respiratory problems, or in certain cases, mortality. CRS is a form of systemic inflammatory response syndrome (SIRS). In SIRS, the substantial activation of endothelial inducible nitric oxide synthase (iNOS) and smooth muscle guanylate cyclase (GC) is observed, which can produce severe hypotension that is unresponsive to conventional vasopressors. Methylene blue (MB) is a direct inhibitor of iNOS and GC and has been used as an effective treatment for VS following cardiothoracic surgery. In the present study, the successful use of MB as a rescue therapy for CRS in a patient receiving rATG following a renal transplant was reported. Following an uneventful cadaveric kidney transplant involving the intravenous (IV) administration of rATG for the induction of immunological tolerance, the patient became markedly hypotensive and tachycardic. The patient required high doses of VP and NE infusions. Following the protocol described for treating refractory VS in post-cardiac surgery patients, the decision was made to initiate the patient on an IV MB infusion. This treatment protocol was shown to improve the hemodynamic status of the patient, which enabled the withdrawal of vasopressors and suggests an important role for methylene blue in the management of refractory VS.

956 - Health-Related Quality of Life (QOL) in Patients with Metastatic Castration-Resistant Prostate Cancer (MCRPC): Cabazitaxel Early Access Program (EAP) Interim Results from Canada

ABSTRACT Background QoL and preference/utility data have not been extensively collected in post-docetaxel (D) mCRPC. Canada collected EQ-5D-3L data in this setting as part of the single-arm multicenter EAP for Cabazitaxel. Methods Between May 2011 and February 2012, 61 evaluable patients (pts) were enrolled at 9 centers. EQ–5D-3L data was collected and analyzed at baseline and after every cycle. EQ-5D health state index (HIS) and visual analog scale (VAS) data were collected. HIS data were converted into utility values using the UK tariff from Dolan 1997. The relationship between baseline ECOG performance status (PS) and EQ-5D values (HIS and VAS) across visits was examined. Results At time of abstract submission, baseline characteristics and EQ-5D data were available for 58 pts: median age 65 years, 94% of pts ECOG PS 0 or 1, 85% had bone metastases, and 45% received at least 6 cycles of cabazitaxel. Significant improvements (p Conclusions Improvements were seen on the EQ-5D in the Pain domain, with more than a third of pts reaching a MID on the EQ-5D by cycle 6. Improvements in pain, a common symptom in mCRPC, directly impact pts' experience of their disease. The poster will present updated data. Disclosure F. Saad: Dr Fred Saad sits on the advisory board for Sanofi Canada and has received consultant's honoraria from Sanofi Canada. He is involved in research projects with Sanofi Canada. E. Winquist: Dr Eric Winquist has received travel funding and consultant's honoraria from Sanofi Canada. He is involved in research projects with Sanofi Canada, M. Girard: Employee with Sanofi Canada, S.S. Sridhar: Dr S.S. Sridhar sits on Advisory Boards and receives Research Funding from Sanofi Canada.

960 - Cabazitaxel Early Access Program (EAP) - Canadian Interim Results: Safety, QOL, and Utility Values in Metastatic Castration Resistant Prostate Cancer (MCRPC)

ABSTRACT Background Cabazitaxel/Prednisone (CbzP) improves survival in docetaxel resistant mCRPC. Canadian investigators collected safety and QoL data for patients (pts) participating in a global single-arm multicenter EAP. Methods Between May 2011 and Feb 2012, 61 evaluable pts were enrolled at 9 centers. Safety and QoL data were collected at baseline and at each cycle. QoL was assessed using the FACT-P and its subscales, EQ 5D-3L, and ESAS questionnaires. Utility values were derived from the EQ 5D-3L. Present pain intensity (PPI) and analgesic scores were assessed using the McGill-Melzack questionnaire. The change from baseline QoL in individual patients was analyzed. Results At the time of analysis, baseline characteristics and safety data were available for the first 33 pts. Median age was 65; 94% were ECOG 0/1; 85% had bone metastases; and 76% had progressed within 3 months of prior docetaxel. Over half (56%) received at least 5 cycles of CbzP. Main grade 3+ toxicities were anemia 3%, leukopenia 3%, and febrile neutropenia 3% (prophylactic and therapeutic G-CSF use was permitted). Incidence of diarrhea (all grades) was 52%, and grade 3+ diarrhea was 3%. No treatment related deaths were reported. Preliminary analyses showed stable QoL and derived utility values over time. A pain subscale of FACT-P, showed improvements in the first 4 cycles; PPI scores improved despite stable analgesic use. Conclusions In this EAP, reflecting routine clinical practice, the main toxicities of CbzP were similar to the TROPIC trial (neutropenia and diarrhea) emphasizing the need for close toxicity monitoring. Preliminary QoL and PPI data support a palliative benefit of CbzP not reported in TROPIC. Updated data with all evaluable pts and percentages of pts meeting important response thresholds will be presented. Disclosure S.S. Sridhar: Dr. Sridhar has served on the advisory board for and is involved in research projects with Sanofi Aventis Canada. E. Winquist: Dr Winquist has received travel funding and consultant's honoraria from Sanofi Canada. He is involved in research projects with Sanofi Canada. C. St.-Laurent Thibault: Catherine Saint-Laurent Thibault is an employee of Sanofi Canada Inc. H. Assi: Membership on an Advisory board, S. Berry: Membership on an advisory board, N. Aucoin: Membership on an advisory board, F. Saad: Dr Fred Saad sits on the advisory board for Sanofi Aventis Canada and has received consultant\\'s honoraria from Sanofi Canada. He is involved in research projects with Sanofi Canada. All other authors have declared no conflicts of interest.

602P - Comparative Budget Impact Analysis of Treatment Sequences in Metastatic Colorectal Cancer (MCRC): From First (1st) Line to Third (3RD) Line Therapies

ABSTRACT Background In the context of personalized cancer care, patients (pts) should receive the therapy that best meets their needs while optimizing the use of healthcare resources. A budget impact model was developed to compare each of the most commonly used mCRC treatment sequences – from 1st line to 3rd line in a Canadian context. Methods This Excel based model considers the price of each agent, the number of cycles per treatment course, the relative dose intensity of the regimens to determine the cost of the most commonly used mCRC therapies and calculates the costs per overall sequence from 1st line to 3rd line. It takes into account the percentage of pts who benefit from a R0 resection post 1st line chemotherapy and who forego subsequent treatments. Factors such as different percentage use of 1st line FOLFOX vs FOLFIRI and pts' volumes per line of therapy are considered in this model. Users can choose the scenarios they would like to examine. Key variables can be extracted through expert opinion, the literature or, to assess real-world local practices, through chart reviews. Results As scenarios considered, the budgetary impact of the 1st line use of FOLFOX or FOLFIRI both given with bevacizumab (bev) on 1st to 3rd line therapy costs was assessed. The relative use of FOLFOX and FOLFIRI with bev was varied from 80% use of FOLFOX and 20% use of FOLFIRI to the opposite. As key variables, the model compares, as 1st line therapy, 18 cycles of FOLFIRI and bev to 8 cycles of mFOLFOX6 followed by 10 cycles of 5FU/LV given with 18 cycles of bev. Also 80% of 1st line pts receive a second line chemotherapy. Assuming a cohort of a 100 pts, when FOLFOX's 1st line use varies from 80% to 20%, the budget varies from $4.14M to $3.85M, with all pts undergoing a R0 resection varying from 11.8 to 8.2 pts. Conclusions Focusing on drug costs only, this dynamic and flexible model goes beyond the comparison of upfront 1st line mCRC costs and considers cascading costs on subsequent lines (2nd and 3rd line) and consequences. It can be used to assess variability in local and provincial practice patterns and their impact on overall budget costs and number of pts benefiting from a R0 resection. Disclosure J.A. Maroun: Advisory board member for Roche and Sanofi. Involved in research projects with Roche and Sanofi. T. Boucher: Employee of Sanofi. K. Alloul: Employee of Sanofi Canada Inc.