Efficacy of administration sequence: Sacituzumab Govitecan and Trastuzumab Deruxtecan in HER2-low metastatic breast cancer.

BACKGROUND: Current guidelines recommend that patients with HER2-low metastatic breast cancer (MBC) receive sequentially two antibody-drug conjugates (ADCs): Sacituzumab Govitecan (SG) and Trastuzumab Deruxtecan (T-DXd), despite a similar payload. However, the effectiveness of one after another is unknown. METHODS: ADC-Low is a multicentre, retrospective study evaluating the efficacy of SG and T-DXd, one after another, with or without intermediary lines of chemotherapy, in patients with HER2-low MBC. RESULTS: One hundred and seventy-nine patients were included: the majority with HR-negative tumours received SG first (ADC1) (n = 100/108) while most with HR-positive tumours received T-DXd first (n = 56/71). Median progression-free survival 2 was short: 2.7 months (95% CI: 2.4-3.3) in the whole population, respectively, 3.1 (95% CI: 2.6-3.6) and 2.2 months (95% CI: 1.9-2.7) for patients receiving T-DXd or SG second (ADC2). Intermediary lines of chemotherapy between ADC1 and ADC2 had no impact. Primary resistance to ADC2 occurred in 54.4% of patients. Certain patients showed initial response to ADC2. CONCLUSIONS: Clinical benefit of sequentially administered SG and T-DXd is limited for most patients. Nevertheless, a subset of patients might benefit-on the short term-from a second ADC. Additional studies are needed to identify patients who could benefit from two ADCs with similar payloads.

Compliance to genomic test recommendations to guide adjuvant chemotherapy decision-making in the case of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, in real-life settings.

BACKGROUND: Genomic tests are a useful tool for adjuvant chemotherapy decision-making in the case of hormone receptor-positive (HR+), and human epidermal growth factor receptor 2-negative (HER2-) breast cancer with intermediate prognostic factors. Real-life data on the use of tests can help identify the target population for testing. METHODS: French multicentric study (8 centers) including patients, all candidates for adjuvant chemotherapy for HR-positive, HER2-negative early breast cancer. We describe the percentage of tests performed outside recommendations, according to the year of testing. We calculated a ratio defined as the number of tests required to avoid chemotherapy for one patient, and according to patient and cancer characteristics. We then performed a cost-saving analysis using medical cost data over a period of 1 year from diagnosis, calculated from a previous study. Finally, we calculated the threshold of the ratio (number of tests required to avoid chemotherapy for one patient) below which the use of genomic tests was cost-saving. RESULTS: A total of 2331 patients underwent a Prosigna test. The ratio (performed test/avoided chemotherapy) was 2.8 [95% CI: 2.7-2.9] in the whole population. In the group following recommendations for test indication, the ratio was 2.3 [95% CI: 2.2-2.4]. In the case of non-abidance by recommendations, the ratio was 3 [95% CI: 2.8-3.2]. Chemotherapy was avoided in 841 patients (36%) following the results of the Prosigna test. The direct medical costs saved over 1 year of care were 3,878,798€ and 1,718,472€ in the group of patients following test recommendations. We calculated that the ratio (performed test/avoided chemotherapy) needed to be under 6.9 for testing to prove cost-saving. CONCLUSION: The use of genomic testing proved cost-saving in this large multicentric real-life analysis, even in certain cases when the test was performed outside recommendations.

ACACIAS 1: The physiological and subjective impacts of high fidelity simulation of the breaking of bad news.

STUDY OBJECTIVE: Breaking bad news (BN) is difficult and necessitates targeted training. To be effective, training may call for High Fidelity Simulation (HFS). This prospective study was conducted to objectively assess the impact of HFS as a tool conducive to the development of clinical competence in situations involving the delivery of bad news. METHODS: This feasibility study was conducted from January to May 2021 and included students in medical oncology and digestive surgery. The subjective and objective impacts of HFS were evaluated by means of a self-administered questionnaire and a wristband, Affect-tag, which recorded several indicators: emotional power (EP), emotional density (DE) and cognitive load (CL) in students undergoing training. RESULTS: Forty-six (46) students with a median age of 25 years (21-34 years) were included. While the participants were effectively and emotionally involved in the HFS training, they were not completely overwhelmed by their emotions, a possible occurrence in this type of program. After two training programs, the students presented with lower EP (P<0.001) and higher DE (P=0.005), while their CL remained stable (P=0.751). The information given in the self-administered questionnaires and the evaluations by outside professionals (actor, nurse, psychologist…) highlighted improved skills. CONCLUSION: Taking into account the emotional parameters observed and the questionnaires collected, HFS can be considered as a suitable and effective tool in the breaking of bad news.

Predictors of women's attendance in a home-based adapted physical activity program during localized breast cancer treatment.

PURPOSE: The objective of this study is to evaluate predictors for attendance in a home-based adapted physical activity (APA) program for women with breast cancer during chemotherapy and radiotherapy treatment. METHODS: This retrospective study was based on two prospective studies (SAPA and APAC), including a total of 73 patients with localized breast cancer during their treatment period. The same APA program lasting 27 weeks was proposed and registered. It consisted of three physical activity sessions (two aerobic and one strength training) per week. The predictors (age, height, body weight, body mass index (BMI), VO2peak, 6-min walking test distance (6MWT), fatigue (MFI), quality of life (EORTC-QLQ), anxiety and depression (HADS), and previous physical activity (IPAQ)) were evaluated before the APA program. RESULTS: According to the multivariate regression analysis, the baseline 6MWT distance and quality of life were predictive of good attendance in the APA program. The univariate analysis showed that initial VO2peak, body weight, BMI, and fatigue influenced attendance in the APA program. CONCLUSIONS: This study helps to better understand the profile of patients who would be participative or non-participative in an APA program. 6MWT distance and quality of life accounted for 19% of attendance in an APA program before the start of treatment. These correlations between the initial predictors of women with breast cancer and their attendance in the APA program during their treatment period make it possible to adapt physical activity professional practices to these patients.

Evolution of overall survival and receipt of new therapies by subtype among 20 446 metastatic breast cancer patients in the 2008-2017 ESME cohort.

BACKGROUND: Treatment strategies for metastatic breast cancer (MBC) have made great strides over the past 10 years. Real-world data allow us to evaluate the actual benefit of new treatments. ESME (Epidemio-Strategy-Medico-Economical)-MBC, a nationwide observational cohort (NCT03275311), gathers data of all consecutive MBC patients who initiated their treatment in 18 French Cancer Centres since 2008. PATIENTS AND METHODS: We evaluated overall survival (OS) in the whole cohort (N = 20 446) and among subtypes: hormone receptor positive, human epidermal growth factor 2 negative (HR+/HER2-; N = 13 590), HER2+ (N = 3919), and triple-negative breast cancer (TNBC; N = 2937). We performed multivariable analyses including year of MBC diagnosis as one of the covariates, to assess the potential OS improvement over time, and we described exposure to newly released drugs at any time during MBC history by year of diagnosis (YOD). RESULTS: The median follow-up of the whole cohort was 65.5 months (95% CI 64.6-66.7). Year of metastatic diagnosis appears as a strong independent prognostic factor for OS [Year 2016 HR 0.89 (95% CI 0.82-0.97); P = 0.009, using 2008 as reference]. This effect is driven by the HER2+ subcohort, where it is dramatic [Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference]. YOD had, however, no sustained impact on OS among patients with TNBC [Year 2016 HR 0.93 (95% CI 0.77-1.11); P = 0.41, using 2008 as reference] nor among those with HR+/HER2- MBC [Year 2016 HR 1.02 (95% CI 0.91-1.13); P = 0.41, using 2008 as reference]. While exposure to newly released anti-HER2 therapies appeared very high (e.g. >70% of patients received pertuzumab from 2016 onwards), use of everolimus or eribulin was recorded in less than one-third of HR+/HER2- and TNBC cohorts, respectively, whatever YOD. CONCLUSION: OS has dramatically improved among HER2+ MBC patients, probably in association with the release of several major HER2-directed therapies, whose penetrance was high. This trend was not observed in the other subtypes, but the impact of CDK4/6 inhibitors cannot yet be assessed.

First case of sternum replacement with a bioceramic prosthesis after radio-induced sarcoma.

Objectives: To date, no "gold standard" technique has been developed for sternum replacement in cases of radioinduced sarcoma, which is a rare and aggressive disease. Current techniques rely on metallic prostheses, meshes, or bone grafts-procedures that that are associated with several complications. We therefore tried a new solution that might simplify and optimize this surgery. Methods: We used a porous alumina ceramic prosthesis (Ceramil: i.ceram, Limoges, France) that has several interesting characteristics, such as osseointegration, biocompatibility, radiolucency, and high mechanical strength. Results: We report the first case of sternal replacement surgery involving the implantation of a ceramic prosthesis after radio-induced sternal sarcoma. In 2005, a 54-year-old woman was diagnosed with local breast cancer for which she underwent all appropriate treatment. Ten years later, she developed radio-induced sarcoma of the sternum. A complete sternal replacement was performed on 24 April 2015, with no postoperative complications. Imaging by 18F-flurodeoxyglucose positron-emission tomography-computed tomography performed 26 months after the surgery showed no local recurrence. The patient seems to have fully recovered and has resumed normal activity. Conclusions: This new technique is promising. For the first time, we highlight the feasibility, safety, and efficacy of sternal replacement using a porous alumina ceramic prosthesis.

[Risk of axillary recurrence after sentinel lymph node biopsy before neoadjuvant chemotherapy in breast cancer]. / Récidive axillaire après prélèvement du ganglion sentinelle avant chimiothérapie néoadjuvante dans le cancer du sein.

OBJECTIVES: In case of large breast cancer, neoadjuvant chemotherapy (NAC) can be performed to reduce the size of the tumor and thus perform a conservative surgery. The place of the sentinel lymph node biopsy (SLNB) in case of NAC is still debated. The main aim of this study is to assess the risk of axillary recurrence after negative SLNB before NAC. METHODS: It is a retrospective, observational and uni-centric study. We included 18 to 80-year-old patients with unilateral breast cancer requiring a NAC and with a negative SLNB before NAC. Our primary endpoint was axillary recurrence. RESULTS: Between August 2006 and October 2016, 64 patients had a negative GS performing before a NAC and did not benefit from axillary dissection after NAC. The average duration of follow-up was 37 months. During our follow-up, we did not find any cases of axillary recurrence. CONCLUSION: This study supports the reliability of lymph node status assessment using the SLNB before CNA.

Two cases of cutaneous drug eruption associated with temozolomide therapy for glioblastoma.

Glioblastoma is the most common form of primary brain cancer. Its treatment involves surgery, radiotherapy, and chemotherapy with temozolomide (tmz), which is an oral alkylating agent. To the best of our knowledge, few dermatologic side effects of tmz have been described. We report two cases of cutaneous drug eruption caused by tmz during and after radiochemotherapy treatment. In the first case, all tests were negative, but the clinical history and the time of onset supported an allergy to tmz. In the second case, an allergy to tmz was proved by a positive lymphocyte activation test. In this context, our study is one of a very few trying to determine dermatologic side effects by applicable tests used in routine practice.