Sacituzumab govitecan in metastatic triple-negative breast cancer patients treated at Institut Curie Hospitals: efficacy, safety, and impact of brain metastases.

BACKGROUND: Sacituzumab govitecan (SG) has been approved by FDA in April 2021 for pre-treated metastatic triple-negative breast cancer (mTNBC), following the ASCENT trial results. METHODS: We set up an ambispective bicentric cohort study to assess the real-world effectiveness and safety of SG in patients with mTNBC treated at Institut Curie Hospitals, with a focus on patients with brain metastases. RESULTS: This study included 99 patients treated through the French Early Access Program to SG from May 2021 to January 2023. Median age was 55 years [26-89], N = 8 patients (8%) had BRCA1/2 mutation, N = 12 (12%) de novo stage IV disease and N = 31 (31%) brain metastases. Patients had previously received a median of two [1-10] lines of treatment in advanced setting. After a median follow-up of 9.7 months, the median progression-free survival (PFS) and overall survival (OS) were 3.9 months (95%CI[3.4-5.0]) and 8.6 months (95%CI[7.1-11.9]), respectively, while objective response rate was 29% (95%CI[21-39]). Among patients with brain metastases, median PFS and OS were 3.7 months (95%CI[2.6-6.2]) and 6.7 months (95%CI[6.3-NR]), respectively, with intracranial tumor responses. Dose reductions were required in N = 17 patients (17%) within a median of three [2-11] cycles, due to gastrointestinal toxicity (N = 6; 6%), hematological toxicity (N = 9; 9%) including febrile neutropenia (N = 2; 2%), liver enzyme elevation (N = 1; 1%), and physical deterioration (N = 1; 1%). There was no related death to SG. CONCLUSIONS: The observed response rate and safety of SG are consistent with the results of the ASCENT trial, with efficacy observed in patients with brain metastases, but observed PFS and OS are numerically shorter.

Advanced prescription of injectable anticancer drugs: Safety assessment in a European Comprehensive Cancer Centre using the risk matrix approach.

AIMS: The purpose of this work was to assess failures in the advanced prescription of parenteral anticancer agents in an adult day oncology care unit with more than 100 patients per day. METHODS: An a priori descriptive analysis was carried out by using the risk matrix approach. After defining the scope in a multidisciplinary meeting, we determined at each step the failure modes (FMs), their effects (E) and their associated causes (C). A severity score (S) was assigned to all effects and a probability of occurrence (O) to all causes. These S and O indicators, were used to obtain a criticality index (CI) matrix. We assessed the risk control (RC) of each failure in order to define a residual criticality index (rCI) matrix. RESULTS: During risk analysis, 14 FMs were detected, and 61 scenarios were identified considering all possible effects and causes. Nine situations (15%) were highlighted with the maximum CI, 18 (30%) with a medium CI, and 34 (55%) with a negligible CI. Nevertheless, among all these critical situations, only three (5%) had an rCI to process (i.e., missed dose adjustment, multiple prescriptions and abnormal biology data); the others required monitoring only. Clinicians' and pharmacists' knowledge of these critical situations enables them to manage the associated risks. CONCLUSIONS: Advanced prescription of injectable anticancer drugs appears to be a safe practice for patients when combined with risk management. The major risks identified concerned missed dose adjustment, prescription duplication and lack of consideration for abnormal biology data.

Errors in prescribing injectable anticancer drugs: benefits of a pharmaceutical long-term monitoring to improve patient safety in a European comprehensive cancer centre.

OBJECTIVES: We aimed to assess the impact of pharmacist interventions on injectable chemotherapy prescription and the safety of early prescription practice in an adult daily care unit. METHODS: Prescription errors were recorded before and after implementing corrective measures. Errors identified from the pre-intervention period (i) were analysed to identify areas for improvement. During the post-intervention period (ii) we compared the errors in anticipated prescription (AP) with those in real-time prescriptions (RTP). We performed Chi-square statistical tests (α=0.05). RESULTS: Before implementing corrective measures (i), 377 errors were recorded (ie, 3.02% of prescriptions). After the implementation of corrective measures (ii), there was a significant decrease in errors, with 94 errors recorded (ie, 1.20% of prescriptions). The error rate in AP and RTP groups was 1.34% and 1.02%, respectively, without a significant difference between the two groups. CONCLUSIONS: This study highlights the importance of prescription review, as well as collaboration between pharmacists and physicians, in reducing prescription errors, whether these prescriptions were anticipated or not.

Application of an Environmental Monitoring to Assess the Practices and Control the Risk of Occupational Exposure to Cyclophosphamide in Two Sites of a French Comprehensive Cancer Center.

OBJECTIVES: The risk of chronic exposure to antineoplastic agents in hospitals, mainly by skin contact with contaminated surfaces, is well established. The aim of this study was to assess indirectly the risk of occupational exposure to antineoplastics drugs at two hospitals by using an environmental monitoring, and to suggest ways of improving the exposure to healthcare workers. METHODS: An observational study of care practices on both sites was carried out. A wipe sampling campaign was then designed to study environmental contamination throughout the chemotherapy process: receipt, storage, compounding, transport, administration, and elimination areas. Samples were analyzed by a validated LC-MS/MS method allowing trace quantification of cyclophosphamide. A guidance 'safe value' of 0.10 ng/cm2 was considered. RESULTS: A total of 293 samples were analyzed, of which 58% were found to be positive. In the compounding units, the drug vials were contaminated before [range = (non-quantifiable [NQ]-0.71) ng/cm2] and after cleaning procedure [(NQ-0.62) ng/cm2], particularly when the flip-off lid was removed during cleaning. The contamination found on manual preparations was operator-dependent: [non-detectable (ND)-3.51] ng/cm2 on infusion bag surfaces; (780.61-24 698.98) ng/cm2 on medication ports. In the case of automated preparations, the average contamination was higher on infusion bag surfaces [(2.43-36.86) ng/cm2] and lower on medication ports [(0.43-7.65) ng/cm2] than manual preparations. Contamination of the analytical control area was also highlighted. In the daily care unit, the contamination was located near the infusion area (armchairs, infusion stands, floor, and patient toilets), and varied somewhat between the two sites, especially on the floor with (0.46-27.32) compared to (ND-0.18) ng/cm2. We did not detect contamination on the transport boxes, on the door handles or in the disposal areas. CONCLUSIONS: The variability of contamination observed between the two sites can be explained in part by the difference in routine practices, especially training of the staff, and cleaning procedures. Findings were communicated to healthcare workers, and news interventions were implemented based on wipe sampling results. This study demonstrated a method for routine environmental monitoring and worker education as a strategy to reduce occupational exposure.

[Adapting to the SARS-CoV2 pandemic: Experience of the Curie Institute]. / S'adapter face à la pandémie SARS-CoV2 : l'expérience de l'Institut Curie.

The Curie Institute exclusively cares for cancer patients, who were considered particularly "vulnerable" from the start of the SARS-CoV 2 pandemic. This pandemic, which took the medical world by surprise, suddenly required the Institute's hospital to undergo rapid and multimodal restructuring, while having an impact on everyone to varying degrees. We will examine here how this hospital has coped, with the concern for a new benefit-risk balance, in times of greater medical uncertainty and scarcity of certain resources, for these "vulnerable" patients but also for their relatives and staff. We will highlight by theme the positive aspects and difficulties encountered, and then what could be useful for other hospitals as the pandemic is ongoing.

First-line Bevacizumab and Paclitaxel for HER2-negative Metastatic Breast Cancer: A French Retrospective Observational Study.

AIM: To assess outcomes in patients treated with first-line bevacizumab-containing therapy for human epidermal growth factor receptor (HER)2-negative metastatic breast cancer (mBC) at a single centre with a homogenous standard-of-care. PATIENTS AND METHODS: Information on patient and disease characteristics, efficacy, and safety was extracted from computer-based records of all patients receiving first-line bevacizumab-paclitaxel at the Curie Institute, Paris, France, between 2008 and 2011. RESULTS: Median progression-free survival in the 116 treated patients was 13.2 months; median overall survival was 38.4 months. Corresponding values were 9.0 and 18.8 months, respectively, in patients with triple-negative mBC, and 19.4 and 58.8 months, respectively, in patients receiving maintenance endocrine therapy. No new safety signals were seen. CONCLUSION: Outcomes in patients treated with bevacizumab-paclitaxel at our center were consistent with efficacy in prospective clinical trials, with notable activity in poor-prognosis disease. Maintenance endocrine or oral therapy with bevacizumab after paclitaxel discontinuation was associated with long-term disease control.

Costs associated with Eribulin treatment for patients with metastatic breast cancer in a comprehensive cancer center in France.

BACKGROUND: There is no standard recommendation for metastatic breast cancer treatment (MBC) after two chemotherapy regimens. Eribulin (Halaven®) has shown a significant improvement in overall survival (OS) in this setting. Its use may however be hampered by its cost, which is up to three times the cost of other standard drugs. We report the clinical outcomes and health care costs of a large series of consecutive MBC patients treated with Eribulin. METHODS: A monocentric retrospective study was conducted at Institut Curie over 1 year (August 2012 to August 2013). Data from patient's medical records were extracted to estimate treatment and outcome patterns, and direct medical costs until the end of treatment were measured. Factors affecting cost variability were identified by multiple linear regressions and factors linked to OS by a multivariate Cox model. RESULTS: We included 87 MBC patients. The median OS was 10.7 months (95%CI = 8.0-13.3). By multivariate Cox analysis, independent factors of poor prognosis were an Eastern Cooperative Oncology Group (ECOG) performance status of 3, a number of metastatic sites ≥ 4 and the need for hospitalization. Per-patient costs during whole treatment were €18,694 [CI 95%: 16,028-21,360], and €2581 [CI 95%: 2226-3038] per month. Eribulin administration contributed to 79% of per-patient costs. CONCLUSIONS: Innovative and expensive drugs often appear to be the main cost drivers in cancer treatment, particularly for MBC. There is an urgent need to assess clinical practice benefits.

Long-term physico-chemical stability of diluted trastuzumab.

Using several complementary analytical methods, we demonstrated that the monoclonal antibody Trastuzumab (Tz), diluted in 0.9% sodium chloride can be stored in polyolefin infusion bags at 4°C or room temperature up to 6 months with no evidence of chemical or physical instability. No aggregation of Tz was observed and its three dimensional structure remains unaltered. Thus, the practical use of diluted Tz can be safely extended to optimize the workload of centralized preparation units and to minimize costs.

Dose standardisation of anticancer drugs.

OBJECTIVE OF THE STUDY: Body size based dosing is often used for prescribing anticancer drugs. However the scientific and the clinical rationales of this historical method have recently been criticized. As a result, alternative dosing strategies have been suggested, as flat-fixed dosing regimens, but not implemented in routine practice. Dose standardisation is a first step in order to rationalise chemotherapy dose calculation. A new method, derived from dose-banding, was developed, taking into account prescription and economic criteria. SETTING: Feasibility and interest of this concept were studied in two French cancer centres Institut Curie and Hôpital Saint-Louis. MAIN OUTCOME MEASURES: The aim of our study was to assess dose standardisation of expensive anticancer drugs in objectives of quality and economy. METHOD: Nine candidate drugs were selected and standardized rounded doses (SRD) were proposed. To determine the specific standard doses of these two centres, two theoretical and practical methods were applied, and then, their results were compared. For each anticancer drug the objective was to fix SRD in order to cover all the doses most frequently prescribed. RESULTS: It has been possible to propose SRD for six of the nine drugs. These SRD have been implemented with the agreement of the medical staff. These doses are, whenever possible, rounded to the nearest vial size, or correspond to a combination of the different strength of the commercial drug. CONCLUSION: Our study shows that dose standardisation is a help to optimise the productivity and improve the organisation of the preparation unit.