Breast cancer is the leading nonhematologic cause of meningeal carcinomatosis (MC). The aim of this study was to report the outcome of patients diagnosed with breast cancer MC and treated in single ...institution by a high-dose intrathecal methotrexate (MTX) regimen.
Ninety-one patients were diagnosed with breast cancer MC from 2000 to 2007. Intrathecal treatment was MTX 15 mg/day (days 1–5), hydrocortisone acetate (day 1) and oral folinic acid (days 1–5), repeated every 2 weeks. Patients and tumor characteristics were associated with the early clinical and biological outcome and with the overall survival (OS).
The median survival was 4.5 months (range 0–53). In multivariate analysis, adverse prognostic factors at diagnosis were performance status >2 P = 0.006, response rate (RR) = 0.33 (0.15–0.71), more than three chemotherapy regimens before MC diagnosis P = 0.03, RR = 0.40 (0.19–0.93), negative hormone receptor status P=0.02, RR = 0.4 (0.19–0.90) and high Cyfra 21-1 level P=0.048, RR = (0.09–0.99). Clinical progression after one cycle and biological response after two cycles were independently associated with OS P < 0.001, RR = 0.09 (0.02–0.37) and P=0.003, RR = 3.6 (1.5–8.5), respectively. We propose a prognostic score in order to define three distinct groups of prognosis.
MC presents a poor prognosis, but 1-year survival rate was 25%. This score may become a useful tool for treatment decision and clinical trials.
Although recent experimental data strongly suggest that platinum-based chemotherapy (PBCT) could improve the outcome of triple-negative breast cancer (TNBC), clinical data are lacking. Here, the ...authors reviewed clinical outcome in patients with metastatic TNBC treated with PBCT.
We conducted a retrospective analysis of all patients (N = 143) treated for metastatic breast cancer with PBCT between 2000 and 2008, at Institut Curie, Paris, France. Ninety-three of them (63.7%) had TNBC. One-hundred twenty patients received cisplatin (CDDP). The main combination used was CDDP–ifosfamide, in 101 patients (70.2%).
Median follow-up was 44 months. For the overall population (N = 143), median overall survival (OS) and median progression-free survival (PFS) were 11 and 5 months, respectively. Objective response rate was 33.3% in the TNBC group versus 22% in non-TNBC, P = 0.1. We observed no difference of OS, PFS and response duration. Other prognostic factors for poor OS were visceral metastasis sites (P < 0.001). One patient died from sepsis during aplasia, 15 had to switch from CDDP to carboplatin because of CDDP-related toxicity.
Metastatic TNBC patients treated with PBCT tended to have a higher response rate, without a significant improvement of PFS or OS, compared with other subtypes. Toxicity was acceptable. Longer observation and further analysis are warranted.
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.
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).
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.
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.
•OS of HER2+ MBC patients keeps improving over time Year 2016 HR 0.52 (95% CI 0.42-0.66); P < 0.001, using 2008 as reference.•This effect seems timely related to the release of drugs demonstrated to improve survival in clinical trials.•OS gains observed in real life among HER2+ MBC patients are at least equivalent to those observed in clinical trials.•YOD had no sustained impact on OS among patients with TNBC and luminal MBC.•The impact of CDK4/6 inhibitors cannot yet be assessed in this cohort.
Randomized clinical trials showed the benefit of adjuvant trastuzumab-based chemotherapy (ATBC) for node-positive and/or >1 cm HER2+ breast carcinomas. No efficacy data have been published on ATBC in ...large series of pT1abN0 HER2+ tumors.
This retrospective study evaluated 276 cases of pT1abN0 HER2+ breast tumors in eight French cancer centers. Factors associated with prognosis and ATBC prescription were analyzed.
A total of 129 cases (47%) were treated with ATBC (ATBC+), 19 with chemotherapy alone, 5 with trastuzumab alone, and 123 (45%) with neither trastuzumab nor chemotherapy (ATBC-). ATBC use was associated with the date of diagnosis (before or after June 2005) and with poor prognostic features. At a median follow-up of 44 months, there were 13 recurrences in the ATBC- group and 2 in the ATBC+ group. ATBC was associated with a significant survival benefit (99% 40-month disease-free survival for ATBC+ versus 93% for ATBC- cases; P = 0.018). Lack of hormone receptors (HRs) and the presence of lymphovascular invasion (LVI) were significantly associated with a poor prognosis and a greater benefit of ATBC.
ATBC was associated with a significantly reduced risk of recurrence in pT1abN0 HER2+ tumors, and was more beneficial in HR- and/or LVI+ tumors.
Insulin-like growth factor (IGF) signaling is implicated in pathogenesis and chemotherapy resistance of epithelial ovarian cancer (EOC). We explored efficacy and safety of adding ganitumab, a ...monoclonal antibody targeting IGF-1R, to carboplatin/paclitaxel (CP) chemotherapy in patients with primary EOC.
Patients were randomly assigned to receive CP/ganitumab (18 mg/kg q3w) or CP/placebo for 6 cycles followed by 6 cycles of single agent ganitumab/placebo maintenance therapy as front-line therapy. Primary endpoint was progression free survival. Secondary endpoints were time to progression and overall survival. Pretreatment samples were prospectively collected for retrospective biomarker analyses.
170 patients enrolled. 165 patients assessable for toxicity. Median PFS was 15.7 months with CP/ganitumab and 16.7 months with CP/placebo (HR 1.23; 95% CI 0.82–1.83, P = 0.313). All grade neutropenia (84.1% vs 71.4%), thrombocytopenia (75.3% vs 57.1%) and hyperglycemia (15.9% vs 2.6%) were more common in the ganitumab group compared to the placebo group. Ganitumab/placebo related serious adverse events were reported in 26.1% of the patients with ganitumab and in 6.5% with placebo. Non-progression related fatal events were more common with ganitumab (5 versus 2 patients). The ganitumab group experienced more dose delays which resulted in lower relative dose intensity of chemotherapy in the experimental group. In an exploratory model IGFBP2 expression was predictive of ganitumab response (treatment interaction; PFS, P = 0.03; OS, P = 0.01).
Addition of ganitumab to CP chemotherapy in primary EOC did not improve PFS. Our results do not support further study of ganitumab in unselected EOC patients.
•Addition of ganitumab to carboplatin paclitaxel chemotherapy in primary EOC did not improve progression-free survival.•Neutropenia, thrombocytopenia and hyperglycemia were more common in the ganitumab group when compared to the placebo group.•Patients with low expression of tumor IGFBP2 may have increased IGF bioavailability and may benefit from ganitumab.•Our results do not support further study of ganitumab in unselected EOC patients.
Treatment of breast cancer meningeal carcinomatosis (MC) relies on intrathecal chemotherapy. Thiotepa is one of the few drugs approved in this setting, although no large cohort has been reported. The ...aim of our retrospective study is to describe survival and prognostic factors of breast cancer patients treated by intrathecal thiotepa. A search in the electronic database of the Institut Curie was performed and retrieved the patients diagnosed with breast cancer MC from 2000 to 2012 and who received at least one intrathecal injection of thiotepa. The standard regimen was intrathecal thiotepa (10 mg) and methylprednisolone (40 mg), repeated every other week. Clinical data were retrieved from the computerized medical file of each patient. Sixty-six patients have been treated with intrathecal thiotepa either as first line or second line of treatment for breast cancer MC. The median overall survival was 4.5 months (range 0.1–50). There was no significant survival difference between patients treated as first or second line. In multivariate analysis, main adverse prognostic factors at diagnosis were performance status >2 (
p
= 0.001, RR = 3.4, 95 % CI 1.6–7.2) and history of more than 3 previous systemic chemotherapy lines (
p
= 0.002, RR = 2.90, 95 % CI 1.50–5.65). After start of the treatment, high primary tumor grade, elevated Cyfra 21-1 levels in the cerebrospinal fluid, and lack of clinical improvement were also independent adverse prognostic factors in multivariate analysis. This is the largest retrospective cohort of breast cancer MC treated by intrathecal thiotepa ever reported. The median overall survival was short but some patients clearly benefited from this treatment, even used as second line.
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