Clinical impact of CA-125 ELIMination rate constant K (KELIM) on surgical strategy in advanced serous ovarian cancer patients.

OBJECTIVES: The modeled CA-125 elimination constant K (KELIM) is a pragmatic early marker of tumor chemosensitivity in ovarian cancer patients treated with neoadjuvant chemotherapy before interval surgery. The primary objective of this study was to assess the prognostic value of KELIM regarding the feasibility of complete surgery, and secondary objectives were to assess the prognostic value of KELIM for the risk of a platinum resistant relapse, progression free survival, and overall survival. METHODS: The study was based on a retrospective cohort of 284 patients treated for an advanced serous high grade ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV, with neoadjuvant chemotherapy, followed by interval surgery, in a comprehensive cancer center. CA-125 concentrations at baseline and during neoadjuvant chemotherapy were collected. The KELIM predictive value regarding the tumor radiological response rate, likelihood of complete surgery, risk of subsequent platinum resistant relapse, progression free survival, and overall survival were assessed with univariate and multivariate tests. RESULTS: In 232 patients, KELIM was an independent and major predictor of the probability of complete surgery and survival. The final logistic regression model, including KELIM (odds ratio (OR) 0.36, 95% confidence interval (CI)0.16 to 0.73, p=0.006) and complete surgery (no vs yes, OR 0.29, 95% CI 0.15 to 0.53, p<0.001), highlighted the complementary impact of chemosensitivity and surgical outcome relative to the complete surgery. In the multivariate analysis, KELIM and complete surgery were significantly associated with a lower risk of early relapse. In the case of an unfavorable KELIM, when surgical efforts allowed complete cytoreduction, median overall survival was similar to that reported in the case of a favorable KELIM (46.3 months (range 34.6-60.3) vs 46.5 months (range 40.6-68.7), respectively). CONCLUSION: Primary tumor chemosensitivity, assessed by the modeled CA-125 KELIM, calculated during neoadjuvant chemotherapy, is a major parameter to consider for decision making regarding interval surgery. Complementary to the RECIST score and laparoscopy, this non-invasive tool, available online, helps tailor the interval surgery strategy according to patient tumor chemosensitivity.

First-line real-world treatment patterns and survival outcomes in women younger or older than 40 years with metastatic breast cancer in the real-life multicenter French ESME cohort.

AIM: To describe first-line treatment patterns, overall survival (OS) and real-world progression-free survival (rwPFS) in young women (<40) with metastatic breast cancer (mBC), as compared to women aged 40-69. MATERIALS AND METHODS: Data on adult women diagnosed with mBC (2008-2017) were extracted from the ESME mBC database (NCT03275311) which includes consecutive patients starting first-line metastatic treatment in one of the 18 French Comprehensive cancer centers. We reported first-line therapeutic strategy and prognostic factors of OS and rwPFS for women aged < 40 and 40-69. RESULTS: In total, 14,897 mBC women were included (1512 aged <40). HR+ /HER2- mBC was the most frequent subtype. First-line treatment differed between young patients and older ones for HR+ /HER2- and Triple Negative (TN) mBC. Median OS for women aged < 40 and 40-69, respectively, was 46.9 and 46.2 months for HR+ /HER2- mBC; 13.5 and 15.2 for TN mBC; and, 60.7 and 55.1 for HER2 + mBC. Median rwPFS under first line treatment was 11.6 and 11.9 months for HR+ /HER2- in women aged < 40 and 40-69, respectively; 5.5 and 5.9 for TN, and, 13.3 and 12.9 for HER2 + . Factors associated with shorter OS and rwPFS were similar for both women aged < 40 and 40-69 and included ≥ 3 metastatic sites, visceral metastases, and longer MFI, with time-varying effects observed for several prognostic factors. CONCLUSION: Young women presented more frequently with TN and HER2 + subtypes and aggressive mBC than women aged 40-69 did. Prognostic factors of OS and rwPFS were quite similar between age groups and mBC subtypes.

Opportunities and Obstacles to the Development of Health Data Warehouses in Hospitals in France: The Recent Experience of Comprehensive Cancer Centers.

Big Data and Artificial Intelligence can profoundly transform medical practices, particularly in oncology. Comprehensive Cancer Centers have a major role to play in this revolution. With the purpose of advancing our knowledge and accelerating cancer research, it is urgent to make this pool of data usable through the development of robust and effective data warehouses. Through the recent experience of Comprehensive Cancer Centers in France, this article shows that, while the use of hospital data warehouses can be a source of progress by taking into account multisource, multidomain and multiscale data for the benefit of knowledge and patients, it nevertheless raises technical, organizational and legal issues that still need to be addressed. The objectives of this article are threefold: 1. to provide insight on public health stakes of development in Comprehensive Cancer Centers to manage cancer patients comprehensively; 2. to set out a challenge of structuring the data from within them; 3. to outline the legal issues of implementation to carry out real-world evidence studies. To meet objective 1, this article firstly proposed a discussion on the relevance of an integrated approach to manage cancer and the formidable tool that data warehouses represent to achieve this. To address objective 2, we carried out a literature review to screen the articles published in PubMed and Google Scholar through the end of 2022 on the use of data warehouses in French Comprehensive Cancer Centers. Seven publications dealing specifically with the issue of data structuring were selected. To achieve objective 3, we presented and commented on the main aspects of French and European legislation and regulations in the field of health data, hospital data warehouses and real-world evidence.

Early Locoregional Breast Surgery and Survival in de novo Metastatic Breast Cancer in the Multicenter National ESME Cohort.

OBJECTIVE: The aim was to evaluate the impact of local surgery performed during the year after MBC diagnosis on patients' outcomes from a large reallife cohort. SUMMARY BACKGROUND DATA: Locoregional treatment for patients with MBC at the time of diagnosis remains debated. METHODS: Women with newly diagnosed, de novo stage IV MBC and who started MBC treatment between January 2008 and December 2014 in one of the 18 French Comprehensive Cancer Centers were included (NCT03275311). The impact of local surgery performed during the first year on overall survival (OS) and progression-free survival (PFS) was evaluated by the Cox proportional hazards model in a 12 month-landmark analysis. RESULTS: Out of 16,703 patients in the ESME database, 1977 had stage IV MBC at diagnosis, were alive and progression-free at 12 months and eligible for this study. Among them, 530 (26.8%) had received primary breast cancer surgery within 12 months. A greater proportion of patients who received surgery had less than 3 metastatic sites than the no-surgery group (90.8% vs 78.2%, P < 0.0001). Surgery within 12 months was associated with treatment with chemotherapy, HER2-targeted therapy (89.1% vs 69.6%, P < 0.0001) and locoregional radiotherapy (81.7% vs 32.5%, P < 0.0001). Multivariable analyses showed that surgery performed within 12 months was associated with longer OS and PFS (adjusted HR [95%CI] = 0.75 [0.61-0.92] and 0.72 [0.63-0.83], respectively), which were also affected by pattern and number of metastatic sites, histological subtype, and age. CONCLUSIONS: In the large ESME cohort, surgery within 1 year after de novo MBC diagnosis was associated with a significantly better OS and PFS.

Comparison of Management and Outcomes in ERBB2-Low vs ERBB2-Zero Metastatic Breast Cancer in France.

Importance: ERBB2-low (ie, ERBB2 immunohistochemistry score of 1+ or 2+ in the absence of ERBB2 gene amplification) breast cancer (BC) is a new entity, with emerging dedicated treatments. Little is known about its prognosis and response to conventional therapy compared with ERBB2-zero breast tumors (ie, those with an immunohistochemistry score of 0). Objective: To compare the outcomes for patients with ERBB2-low metastatic BC (MBC) with those of patients with ERBB2-zero MBC. Design, Setting, and Participants: This cohort study was conducted from the Epidemiological Strategy and Medical Economics MBC platform and included patients with MBC treated between 2008 and 2016 in 18 French comprehensive cancer centers. The data analysis was conducted from July 16, 2020, to April 1, 2022. Main Outcomes and Measures: The main outcome was overall survival (OS), and the secondary outcome was progression-free survival under first-line treatments (PFS1). Results: The median (range) age was 60.0 (22.0-103.0) years. Among 15 054 patients with MBC, 4671 (31%) had ERBB2-low MBC and 10 383 (69%) had ERBB2-zero MBC. The proportion of ERBB2-low cancers was higher among patients with hormone receptor-positive MBC than those with hormone receptor-negative disease (4083 patients [33.0%] vs 588 patients [21.0%]). With a median follow-up of 49.5 months (95% CI, 48.6-50.4 months), the median OS of the ERBB2-low group was 38.0 months (95% CI, 36.4-40.5 months) compared with 33.9 months (95% CI, 32.9-34.9 months) for the ERBB2-zero group (P < .001). After adjustment for age, visceral metastases, number of metastatic sites, de novo disease, period of care, and hormone receptor status, patients with ERBB2-low MBC had slightly better OS compared with patients with ERBB2-zero MBC (adjusted hazard ratio, 0.95; 95% CI, 0.91-0.99; P = .02). In contrast, PFS1 did not differ by ERBB2 status (adjusted hazard ratio, 0.99; 95% CI, 0.95-1.02; P = .45). No significant differences in OS and PFS1 were observed in multivariate analyses by hormone receptor status and types of frontline treatment. Conclusions and Relevance: In this large cohort study, patients with ERBB2-low MBC had a slightly better OS than those with completely ERBB2-zero tumors, but identical PFS1, which could help guide treatment selection.

Progression-free survival on endocrine therapy, before or after chemotherapy, in hormone receptor-positive HER2-negative metastatic breast cancer.

PURPOSE: A major question when treating HR+/HER2- metastatic breast cancer (MBC) is whether early introduction of chemotherapy (CT) increases endocrine resistance. We aimed to describe progression-free survival (PFS) under first endocrine therapy (ET) depending on whether given before or after CT in a large nationwide cohort, in the pre-CDK era. METHODS: The real-life retrospective ESME database includes all patients with MBC whose first-line treatment was initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. Our primary objective was to compare PFS from start of first ET in patients with HR+/HER2- MBC who received ET or CT first. RESULTS: We identified 6293 patients who received at least one ET line during their first two therapeutic lines for MBC. As first-line therapy, 3832 (60.9%) received ET alone (ET1 1st group), whilst 2461 (39.1%) received CT, including 2024 patients (32.2%) with maintenance ET after CT (ET1 after CT group). Median PFS under first ET was 12.4 months (95% CI 11.9-13.1) in ET 1st group vs. 12.6 months in ET1 after CT group (95% CI 12.1-13.4), HR 0.96 (95% CI 0.90-1.01, P = 0.1277). CONCLUSIONS: PFS under first ET appears identical whether prescribed before or after chemotherapy. These data suggest chemotherapy does not promote endocrine resistance.

Real-world Evaluation of Oral Vinorelbine in the Treatment of Metastatic Breast Cancer: An ESME-MBC Study.

BACKGROUND/AIM: Vinorelbine is indicated for use in the treatment of MBC as a single agent or in combination but there is little real world data on this molecule and even less on its oral form. We exploited the Unicancer Epidemiology Strategy Medical-Economics (ESME) metastatic breast cancer (MBC) database to investigate current patterns of use of oral vinorelbine (OV), as well as outcomes of patients receiving this drug. PATIENTS AND METHODS: Data were collected retrospectively from women and men treated for MBC between 2008 and 2014 at one of 18 French Comprehensive Cancer Centres. The efficacy of OV was evaluated in terms of progression-free (PFS) and overall survival (OS) and treatment duration. The population and patterns of OV usage were also described. RESULTS: A total of 1806 patients (11% of the ESME MBC database) were included in this analysis. OV was prescribed as monotherapy (46%) or in combination (29%), especially with capecitabine. mainly in later treatment lines. Median PFS was 3.3 months: 2.9 months for single agent, 3.6 months for combination therapy. Median OS was 40.9 months. CONCLUSION: Real-world data offer complementary results to the data from traditional clinical trials, but they concern a much larger population. In this ESME MBC cohort, OV was only prescribed to a small subset of MBC patients. OV was mainly given as single agent to patients with heavily pre-treated MBC; less commonly, it was co-administered with capecitabine or anti-HER2, in earlier lines of therapy. PFS was modest but in line with previous reports.

Management and outcome of male metastatic breast cancer in the national multicenter observational research program Epidemiological Strategy and Medical Economics (ESME).

BACKGROUND AND AIMS: Because of its low prevalence, metastatic breast cancer (MBC) in males is managed based on clinical experience with women. Using a real-life database, we aim to provide a comprehensive analysis of male MBC characteristics, management and outcome. METHODS: The Epidemiological Strategy and Medical Economics Data Platform collected data for all men and women ⩾18 years with MBC in 18 participating French Comprehensive Cancer Centers from January 2008 to November 2016. Demographic, clinical, and pathological characteristics were retrieved, as was treatment modality. Men were matched 1:1 to women with similar characteristics. RESULTS: Of 16,701 evaluable patients, 149 (0.89%) men were identified. These men were older (median age 69 years) and predominantly had hormone receptor HR+/HER2- disease (78.3%). Median overall survival (OS) was 41.8 months [95% confidence interval (CI: 26.9-49.7)] and similar to women. Median progression-free survival (PFS) with first-line therapy was 9.3 months [95% CI (7.4-11.5)]. In the HR+/HER2- subpopulation, endocrine therapy (ET) alone was the frontline treatment for 43% of patients, including antiestrogens (n = 19), aromatase inhibitors (n = 15) with luteinizing hormone-releasing hormone (LHRH) analogs (n = 3), and various sequential treatments. Median PFS achieved by frontline ET alone was similar in men [9.8 months, 95% CI (6.9-17.4)] and in women [13 months, 95% CI (8.4-30.9)] (p = 0.80). PFS was similar for HR+/HER2- men receiving upfront ET or chemotherapy: 9.8 months [95% CI (6.9-17.4)] versus 9.5 months [95% CI (7.4-11.7)] (p = 0.22), respectively. CONCLUSION: MBC management in men and women leads to similar outcomes, especially in HR+/HER2- patients for whom ET should also be a cornerstone. Unsolved questions remain and successfully recruiting trials for men are still lacking.

Eribulin mesylate for the treatment of late-stage breast cancer.

INTRODUCTION: Chemotherapy agents, particularly anthracycline and taxane, have demonstrated their significance in metastatic breast cancer. However, improving overall survival in late-stage breast cancer remains a challenge. Eribulin mesylate, a new chemotherapy agent, has a proven significance in this setting. Eribulin mesylate is a synthetic analog of a macrolide isolated from a marine sponge. It inhibits microtubule polymerization, inducing mitosis arrest and apoptosis, and aggregates soluble tubulin in nonproductive form. In Phase II studies, this drug has shown a partial and stable response. The Phase III EMBRACE study showed that eribulin mesylate improved overall survival, compared with the physician's choice of treatment, in women who had received two to five prior chemotherapy regimens, including anthracycline and taxane for advanced breast cancer (median overall survival: 13.1 versus 10.6 months HR 0.81, p = 0.041). This compound is well tolerated. The most common adverse event is neutropenia. AREAS COVERED: This paper provides an introduction to the drug, eribulin mesylate, along with an overview of the current drug market for late-stage breast cancer; it also reviews its pharmacodynamics, pharmacokinetics and clinical efficacy. EXPERT OPINION: Currently, eribulin mesylate is only the third single-agent chemotherapy that has improved overall survival (after anthracycline and taxane) in advanced breast cancer. These results, particularly in heavily pretreated breast cancer, suggest that this drug could become a new standard in the treatment of metastatic breast cancer, and should, therefore, be further developed in its earlier stages.

Oxaliplatin-based hyperthermic intraperitoneal chemotherapy in primary or recurrent epithelial ovarian cancer: A pilot study of 31 patients.

BACKGROUND: The feasibility and safety of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) associated with cytoreductive surgery (CRS) was assessed in patients with peritoneal carcinomatosis resulting from primary advanced or relapsing epithelial ovarian cancer (EOC). METHODS: Thirty-one patients received neoadjuvant platin-based chemotherapy followed by oxaliplatin-based HIPEC associated with CRS as consolidation of primary therapy (n = 19) or for relapsing disease (n = 12). Grade 3/4 complications were recorded according to National Cancer Institute definitions. RESULTS: Median peritoneal carcinomatosis index (PCI) was 2.7 after neoadjuvant chemotherapy. Mean duration of surgery was 352 min (range 105-614) and median hospital stay was 11 days (range 6-87). Grade 3 toxicity was observed in nine patients: five required repeat surgery, two an invasive procedure, four rehospitalization, and three a return to the ICU. No grade 4 toxicity occurred, excepted one hypokalemia. Median progression-free survival (PFS) for primary advanced EOC was 13.2 months and 1-year PFS was 59.3%. Median PFS for relapsing patients was 14.3 months and 1-year PFS was 54.4%. CONCLUSION: CRS with oxaliplatin-based HIPEC is feasible and relatively safe in recurrent and primary EOC. HIPEC after neoadjuvant chemotherapy reduces the PCI and decreases the number of surgical procedures and morbidity. Further evaluations of this procedure are required to assess the survival benefits.