Treatment and outcomes of patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have dramatically improved over the past 20 years. This work evaluated treatment patterns and outcomes ...according to age.
Women who initiated a treatment for HER2+ MBC between 2008 and 2016 in one of the 18 French comprehensive centers part of the ESME program were included. Objectives were the description of first-line treatment patterns, overall survival (OS), first-line progression-free survival (PFS), and prognostic factors among patients aged 70 years or more (70+), or less than 70 (<70).
Of 4045 women diagnosed with an HER2+ MBC, 814 (20%) were 70+. Standard first-line treatment (chemotherapy combined with an anti-HER2 therapy) was prescribed in 65% of 70+ versus 89% of <70 patients (p < 0.01). Median OS was 49.2 (95% CI, 47.1–52.4), 35.3 (95% CI, 31.5–37.0) and 54.2 months (95% CI, 50.8–55.7) in the whole population, in patients 70+ and <70, respectively. Corresponding median PFS1 were 12.8 (95% CI, 12.3–13.3), 11.1 (95% CI, 10.0–12.3) and 13.2 months (95% CI, 12.7–13.9), respectively. In 70+ women, initiation of non-standard first-line treatment had an independent detrimental time-varying effect on both OS and PFS (HR on OS at 1 year: chemotherapy without anti-HER2 2.79 95% CI: 2.05–3.79; endocrine therapy and/or anti-HER2 1.96 95% CI: 1.43–2.69).
In this large retrospective real-life database, older women with HER2+ MBC received standard first-line treatment less frequently than younger ones. This was independently associated with a worse outcome, but confounding factors and usual selection biases cannot be ruled out.
•Only 65% of women aged 70+ with HER2+ MBC receive a standard first-line treatment.•Median PFS1 of women 70+ with HER2+ MBC is 11.1 months (95% CI, 10.0–12.3) vs 13.2 (95% CI, 12.7–13.9) for younger ones.•Non-standard first-line treatment has a detrimental time-varying effect on both OS and PFS.
The prognostic assessment of older cancer patients is complicated by their heterogeneity. We aimed to assess the prognostic value of routine inflammatory biomarkers.
A pooled analysis of prospective ...multicenter cohorts of cancer patients aged ≥70 was performed. We measured CRP and albumin, and calculated Glasgow Prognostic Score (GPS) and CRP/albumin ratio. The GPS has three levels (0 = CRP ≤ 10 mg/L, albumin ≥ 35 g/L, i.e., normal values; 1 = one abnormal value; 2 = two abnormal values). One-year mortality was assessed using Cox models. Discriminative power was assessed using Harrell's C index (C) and net reclassification improvement (NRI).
Overall, 1800 patients were analyzed (mean age: 79 ± 6; males: 62%; metastases: 38%). The GPS and CRP/albumin ratio were independently associated with mortality in patients not at risk of frailty (hazard ratio 95% confidence interval = 4.48 2.03-9.89 for GPS1, 11.64 4.54-29.81 for GPS2, and 7.15 3.22-15.90 for CRP/albumin ratio > 0.215) and in patients at risk of frailty (2.45 1.79-3.34 for GPS1, 3.97 2.93-5.37 for GPS2, and 2.81 2.17-3.65 for CRP/albumin ratio > 0.215). The discriminative power of the baseline clinical model (C = 0.82 0.80-0.83) was increased by adding GPS (C = 0.84 0.82-0.85; NRI events (NRI+) = 10% 2-16) and CRP/albumin ratio (C = 0.83 0.82-0.85; NRI+ = 14% 2-17).
Routine inflammatory biomarkers add prognostic value to clinical factors in older cancer patients.
The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) ...metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m
) in the "3 plus 3" dose-escalation part. During expansion, they received 60 mg/m
of NPLD every 3 weeks (Q3W) plus standard doses of T-DM1. The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m
administered IV Q3W. No clinically relevant worsening of cardiac function was observed. Among all evaluable patients, the overall response rate was 40.0% (95%CI, 16.3-67.7) with a median duration of response of 6.9 months (95%CI, 4.8-9.1). Clinical benefit rate was 66.7% (95%CI, 38.4-88.2) and median progression-free survival was 7.2 months (95%CI, 4.5-9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients.
In early 2020, the book "Breast cancer: Global Quality Care" was published by Oxford University Press. In the year since then, publications, interviews (by ecancer), presentations, webinars, and ...virtual congress have been organized to disseminate further the main message of the project: "A call for Fairer Breast Cancer Care for all Women in a Globalized World." Special attention is paid to increasing the "value-based healthcare" putting the patient in the center of the care pathway and sharing information on high-quality integrated breast cancer care. Specific recommendations are made considering the local resource facilities. The multidisciplinary breast conference is considered "the jewel in the crown" of the integrated practice unit, connecting multiple specializations and functions concerned with patients with breast cancer. Management and coordination of medical expertise, facilities, and their interfaces are highly recommended. The participation of two world-leading cancer research programs, the CONCORD program and Breast Health Global Initiative, in this project has been particularly important. The project is continuously under review with feedback from the faculty. The future plan is to arrive at an openaccess publication that is freely available to all interested people. This project is designed to help ease the burden and suffering of women with breast cancer across the globe.
Background:
Breast cancer (BC) in young women merits a specific approach given the associated fertility, genetic and psychosocial issues. De novo metastatic breast cancer (MBC) in young women is an ...even more serious condition, with limited data available.
Methods:
We evaluated management of women aged ⩽40 years with de novo MBC in a real-life national multicentre cohort of 22,463 patients treated between 2008 and 2016 (NCT0327531). Our primary objective was to compare overall survival (OS) in young women versus women aged 41–69 years. The secondary objectives were to compare first-line progression-free survival (PFS1) and to describe treatment patterns.
Results:
Of the 4524 women included, 598 (13%) were ⩽40 years. Median age at MBC diagnosis was 36 years (range = 20–40). Compared with women aged 41–69 years, young women had more grade III tumours (49% versus 35.7%, p < 0.0001), human epidermal growth factor receptor 2 amplified (HER2+) disease (34.6% versus 26.4%, p < 0.0001) and HR–/HER2– disease known as “triple negative breast cancer” (TNBC) (17.1% versus 12.7%, p < 0.0001). BRCA testing was performed for 260 young women, with a BRCA1/2 mutation in 44 (17% of those tested) In young HR+/HER2– patients, chemotherapy (CT) was given as the frontline treatment more frequently compared with older ones (89.6% versus 68.8%, respectively, p < 0.0001). After median follow-up of 49.7 months (95% confidence interval, CI = 48.0–51.7), the median OS of young women was 58.5 months, 20.7 months and not attained in HR+/HER2–, TNBC and HER2+ subgroups, respectively. After adjustment for histological subtype, tumour grade, and number and type of metastasis, young women had significantly better OS compared with older ones, except for the TNBC subgroup, for which the outcome was similar. PFS1 was statistically different only in the TNBC subgroup, with 7.8 months for young women and 6.3 months for older women (p = 0.0015).
Conclusion:
De novo MBC affects a significant proportion of young women. A subgroup of these patients achieves long OS and merits multidisciplinary care.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• The optimal infusion duration for ifosfamide remains to be determined.
• No differences according to time of infusion have been identified in traditional ...pharmacokinetic endpoints, such as area under the curve.
• The impact on pharmacodynamics has never been modelled or correlated with pharmacokinetics.
WHAT THIS STUDY ADDS
• The pharmacokinetics and pharmacodynamics of ifosfamide and its main metabolites can both be modelled with no influence of infusion duration.
• Pharmacodynamic modelling (renal and haematological toxicity) allows further simulations of new schedules with favourable toxicity profiles.
AIMS
To model the pharmacokinetics and pharmacodynamics of ifosfamide and its key metabolites. The pharmacodynamic parameters included were renal toxicity and myelosuppression measured using urinary β2‐microglobulin (BMG) and absolute neutrophil count (ANC), respectively.
METHODS
Seventeen patients were enrolled into an n = 1 randomized trial during two consecutive cycles of ifosfamide 9 g m−2 during each cycle given by a 3 h or 72 h infusion. Data were analyzed using NONMEM.
RESULTS
Ifosfamide and metabolite concentration–time profiles were described by a one‐compartment open‐model with auto‐induction of clearance. BMG and ANC time‐courses were related to ifosfamide concentration via indirect response models.
CONCLUSIONS
This modelling allowed the simulation of weekly schedules of flat doses with favourable myelotoxic profiles.
Abstract Purpose Optimal duration of adjuvant chemotherapy in the treatment of early-stage breast cancer remained to be investigated rigorously for the standard regimens in widespread use in North ...America (doxorubicin/cyclophosphamide, AC) and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles of FEC 100 present an advantage, or not, compared with only four cycles was tested directly in a phase III prospective multicentre trial. Patients and methods Between 2002 and 2006, 1515 women between 18 and 65°years of age, with node negative N(−) high-risk early-stage breast cancer, were included in the study following breast surgery and axillary lymph node dissection or procedure by sentinel node technique. Inclusion in the study required tumour size T ≥ 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen receptor/progesterone receptor (ER– and PR–), Scarff-Bloom-Richardson (SBR) grade II or III and age ≤ 35°years. Patients were randomly assigned to either six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an absolute difference ≥6% in disease-free survival (DFS) at 5°years. Results At 6.1°years median follow-up, with 91 (12%) events recorded in Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95% 0.89–1.56, P = .24) and overall survival (OS) (HR = 1.39; CI 95% 0.91–2.13, P = .12). Conclusion Differences in chemotherapy duration did not induce notably different outcomes in our cohort of high-risk patients. Clinical trial registry number NCT00055679 , Agence National de Sécurité du Médicament (ANSM) – France.
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