Trastuzumab deruxtecan in previously treated HER2-positive metastatic or unresectable breast cancer: Real-life data from the temporary use authorization program in France.

BACKGROUND: Early access program (formerly cohort Temporary Authorization for Use) was granted for trastuzumab deruxtecan (T-DXd) in France based on DESTINY-Breast01 trial which demonstrated its efficacy and safety in HER2-positive metastatic/unresectable breast cancer after ≥2 anti-HER2-based regimens received at metastatic stage. METHODS: This multicenter real-world early access program included HER2-positive metastatic/unresectable breast patients pretreated with at least two lines of anti-HER2 regimens who received T-DXd 5.4 mg/kg intravenously in monotherapy every 3 weeks. RESULTS: Four hundred and fifty-nine patients (median age, 58 years; hormone receptor-positive, 67%; brain metastases, 28.1%) received T-DXd. Before inclusion, 81.7% of patients had radiation therapy and 76.5% had undergone surgery. Median number of prior metastatic treatment lines was four (range, 2-22); 99.8% patients had received trastuzumab, 94.8% trastuzumab emtansine and 79.3% pertuzumab. Follow-up was performed from September 30, 2020 to March 30, 2021; when the early access program stopped, the median duration of T-DXd treatment was 3.4 (range, 0-7.8) months. In 160 patients with available tumor assessment, objective response rate was 56.7% and 12.1% had progression. In 57 patients with available brain tumor assessment, complete or partial intracranial response was reported for 35.7% patients and 5.4% had progression. A total of 17 (3.7%) patients with interstitial lung disease (ILD) was reported with no cases of ILD-related death. CONCLUSIONS: In this early access program in patients with heavily pretreated HER2-positive metastatic/unresectable breast cancer, T-DXd had antitumor activity with a similar response to that reported in previous clinical studies. T-DXd was well tolerated and no new safety signals were observed.

Recommandations francophones pour la pratique clinique concernant la prise en charge des cancers du sein de Saint-Paul-de-Vence 2022-2023.

With more than 60,000 new cases of breast cancer in mainland France in 2023 and 8% of all cancer deaths, breast cancer is the leading cancer in women in terms of incidence and mortality. While the number of new cases has almost doubled in 30 years, the percentage of patients at all stages alive at 5 years (87%) and 10 years (76%) testifies to the major progress made in terms of screening, characterisation and treatment. However, this progress, rapid as it is, needs to be evaluated and integrated into an overall strategy, taking into account the characteristics of the disease (stage and biology), as well as those of the patients being treated. These are the objectives of the St Paul-de-Vence recommendations for clinical practice. We report here the summary of the votes, discussions and conclusions of the Saint-Paul-de-Vence 2022-2023 RPCs.

Febrile neutropenia prophylaxis, G-CSF physician preferences: discrete-choice experiment.

OBJECTIVES: Febrile neutropenia (FN) commonly occurs during cancer chemotherapy. Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) is known to reduce the severity and incidence of FN and infections in patients with cancer. Despite the proven efficacy, G-CSFs are not always prescribed as recommended. We performed a discrete-choice experiment (DCE) to determine what factors drive the physician preference for FN prophylaxis in patients with cancer undergoing chemotherapy. METHODS: Attributes for the DCE were selected based on literature search and on expert focus group discussions and comprised pain at the injection site, presence of bone pain, associated fever/influenza syndrome, efficacy of prophylaxis, biosimilar availability, number of injections per chemotherapy cycle and cost. Oncologists, in a national database, were solicited to participate in an online DCE. The study collected the responses to the choice scenarios, the oncologist characteristics and their usual prescriptions of G-CSFs in the context of breast, lungs and gastrointestinal cancers. RESULTS: Overall, the responses from 205 physicians were analysed. The physicians were mainly male (61%), with ≤20 years of experience (76%) and working only in public hospitals (73%). The physicians prescribe G-CSF primary prophylaxis for 32% of patients: filgrastim in 46% and pegfilgrastim in 54%. The choice of G-CSF for primary and secondary prophylaxis was driven by cost and number of injections. Biosimilars were well accepted. CONCLUSION: Cost and convenience of G-CSF drive the physician decision to prescribe or not G-CSF for primary and secondary FN prophylaxes. It is important that these results be incorporated in the optimisation of G-CSF prescription in the clinical setting.

[Granulocyte- colony stimulating factor (G-CSF) use in clinical practice in patients receiving chemotherapy for breast cancer: The Opaline Study]. / Description des modalités pratiques de prescription d'un facteur de croissance de la lignée granulocytaire (G-CSF) chez les patientes recevant une chimiothérapie pour un cancer du sein : étude Opaline.

OBJECTIVES: To describe the French routine use of G-CSF in patients treated for breast cancer as per the EORTC recommendations. PATIENTS AND METHODS: A prospective multicenter observational study conducted between February 2008 and September 2009 in 869 breast cancer patients treated by chemotherapy (CT) and for whom G-CSF treatment will be delivered in primary (PP) or secondary prophylaxis. RESULTS: The mean age was 55 years. A total of 80.3% of CT was in neoadjuvant/adjuvant setting (NAS). PP was delivered in 78.9% of the NAS patients and 67.5% in metastatic situation. Of the 702 evaluable patients, incidences of severe (SN) and febrile neutropenias (FN) in patients who received PP were 9.3% and 4.2%, respectively. In patients who did not received G-CSF at first cycle, SN and FN were 12.4% and 7.3%, respectively. The use of PP was mainly driven by the type of CT for patients treated in the NAS and by patient or disease related risk factors in the locally advanced/metastatic setting. CONCLUSION: This study has shown that the use of G-CSF was in accordance with the 2010 updates of the EORTC recommendations. However, G-CSF appears more widely used in the routine practice.

Management of anemia in advanced breast and lung cancer patients in daily practice: results of a French survey.

INTRODUCTION: The purpose of this French survey was to evaluate the adherence to the guidelines (European Organisation for Research and Treatment of Cancer [EORTC]; American Society of Clinical Oncology [ASCO]; French Standards, Options, and Recommendations [SOR]; European Society of Medical Oncology [ESMO]; Food and Drug Administration [FDA]; and National Comprehensive Cancer Network [NCCN]) for the use of erythropoiesis-stimulating agents (ESAs) in the management of chemotherapy- induced anemia for patients with advanced breast and lung cancers. METHODS: Two-hundred patients were recruited for each malignancy. The collected items were characteristics of ESA initiation, treatment, adjustment, and discontinuation. Metastatic breast cancer and stage IIIb/IV lung cancer patients who had received chemotherapy were eligible. The endpoint was to compare French daily practices with national and international guidelines. RESULTS: From November 2010 to December 2010, 185 breast cancer and 227 lung cancer files were collected. The main reason of ESA initiation was the correction of anemia (49% and 44%, respectively). The median baseline value of hemoglobin was 9.5 g/dL, and the median target value was 12 g/dL. The mean duration of treatment was 12 and 14 weeks, respectively. The mean gain of hemoglobin was 2.3 g/dL and 1.9 g/dL, respectively. In the breast cancer population, two patients (1%) developed a thromboembolic event, which is lower than what has been described in the literature. An iron supplement was prescribed in 55% of patients with breast cancer and 49% of those with lung cancer, with about one-third administered intravenous iron. The interruption of ESA and chemotherapy was synchronous in about 20% of cases, and was earlier in lung cancer patients than in breast cancer patients. CONCLUSION: The quality and the rigor of the sampling represent one of the key points of this survey. The French and international guidelines for the use of ESA were well respected by the physicians. Overall, the management of chemotherapy-induced anemia was improved compared with what was described in the historical surveys (European Cancer Anaemia Survey [ECAS], French Anaemia Cancer Treatment [F-ACT]).

Ectopic pregnancy in a breast cancer patient receiving trastuzumab.

Cervico-isthmic pregnancy is a rare form of ectopic pregnancy with a poor obstetrical prognosis, whose mechanism remains unclear. Preclinical data indicate that HER-2 plays a major role in embryo implantation. We report a case of cervico-isthmic pregnancy occurring during treatment with trastuzumab (Herceptin, a monoclonal antibody to HER-2). A 43-year-old woman presented with abnormal vaginal bleeding, while she was receiving trastuzumab for the last 14 months as an adjuvant therapy for a node-positive, HER-2 positive breast cancer. The diagnosis of evolutive cervico-isthmic pregnancy was confirmed by iterative ultrasonographic examinations. Given the poor obstetrical prognosis, the patient underwent voluntary abortion. The use of trastuzumab during pregnancy is still poorly documented, and its safety is not yet established. Given the importance of HER-2 in embryo implantation and fetal development, its putative role in this abnormal embryo implantation should be discussed.

[Management of anaemia in patient with cancer: results of the F-ACT study (French Anaemia Cancer Treatment)]. / Prise en charge de l'anémie chez les patients présentant une pathologie maligne: résultats de l'étude F-ACT (French Anaemia Cancer Treatment).

Anaemia is one of the most dreaded complications among patients with malignant pathologies. Its causes can be varied and whatever its severity, the impact on the quality of life of the patient remains essential. However, the epidemiologic data concerning anaemia are very few in the literature. This is why we carried out a large national survey about the prevalence and the management of anaemia among patients with malignant diseases. The F-ACT (French Anaemia Cancer Treatment) study is a retrospective observational multicentric study conducted with 178 experts practicing in 112 centers or units treating patients with solid tumours and/or malignant haematological diseases. Control over one day standard of consultation for each questioned expert, 2 782 patients were enrolled, including 1 892 (68%) patient with solid tumour and 890 (27%) patient with malignant haematological disease. The median age was 61 years (range : 18-93 years) including 1 335 women (48%) and 1 447 men (52%). A the date of enrollment, the median level of haemoglobin (Hb) was 11,6 g/dl (range: 5,2-18,5 g/dl) and 44% of patient had a level of Hb < 11 g/dl. An anaemia was found in all the cancer localizations and whatever the stage or the therapeutic status of the disease. Approximately 2/3 of the anaemic patients received treatment by erythropoiesis stimulating agent (ESA) and approximately 17% of them did not receive any specific treatment for this anaemia. The median level of Hb at the introduction of the ESA was 10 g/dl. These results, compared with those reported in study ECAS (European Cancer Anaemia Survey) in 2001, seem to show an improvement in the management of anaemia and the use of the ESA, in particular an earlier introduction of this type of treatment since the appearance of anaemia.