PANHER study: a 20-year treatment outcome analysis from a multicentre observational study of HER2-positive advanced breast cancer patients from the real-world setting (original) (raw)
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COMPARISON OF RESPONSE TO TREATMENT IN LINES SUBSEQUENT TO T-DM1 IN PATIENTS WITH METASTATIC HER2 POSITIVE BREAST CANCERS (Atena Editora), 2023
Introduction: Breast cancer has a strong epidemiological impact. Approximately 20% of them are HER-2 positive. In the metastatic setting, first-line treatment with pertuzumab, trastuzumab and taxane is consolidated by the CLEOPATRA study and second-line treatment, until recently, with trastuzumab-emtansine (T-DM1) by the EMILIA study. Sequencing after using T-DM1 lacks consistent information. Objectives: the primary outcome was the comparison of the response rate of patients undergoing subsequent line to T-DM1, in HER2-positive metastatic breast cancer. Secondary objectives were to compare Overall Survival (OS), Progression-Free Survival to T-DM1 (PFS), Progression-Free Survival to subsequent line (PFS2), Time to Treatment Failure (TFT) and adverse events. Methods: Retrospective, single-center study, including 67 patients with HER2-positive metastatic breast cancer exposed to T-DM1 between August 2013 and December 2021. Of the 67 patients, 38 received subsequent lines of treatment, with a median follow-up of 34 months. Treatments subsequent to T-DM1 were divided into 3 groups: Group 1 = capecitabine + lapatinib (21 patients); Group 2 = trastuzumab-deruxtecan (5 patients) and Group 3 = anti-HER2 associated with chemotherapy (12 patients). Results: The response rate was 19% in group 1, 60% in group 2 and patients in group 3 showed disease stability. The DFS was 15 months. The median OS of T-DM1 was 47 months. No patient in Group 2 experienced progression or death. There was no significant difference in PFS between groups 1 and 3. Conclusion: The response rate varied according to the subsequent line, being favorable to trastuzumab-deruxtecan, which also had lower toxicity. Comparison of OS between groups was not possible due to the number of patients included and events.
Cancer Biology & Therapy
We carried out a retrospective observational study of 264 HER2-positive advanced breast cancer (ABC) patients to explore the efficacy of first-line treatment with pertuzumab/trastuzumab/taxane in realworld setting. Survival data were analyzed by Kaplan Meier curves and log rank test. Median follow-up, length of pertuzumab/trastuzumab/taxane treatment and of pertuzumab, trastuzumab maintenance were 21, 4 and 15 months, respectively. The response rate was 77.3%, and the clinical benefit rate 93.6%. Median progression-free survival (mPFS) was 21 months, and median overall survival (mOS) was not reached. When comparing patients by trastuzumab-pretreatment, similar PFS were observed, although a longer OS was reached in trastuzumab-naïve patients (p = 0.02). Brain metastases at baseline and their development in course of therapy were associated with significantly shorter PFS (p = 0.0006) and shorter OS, although at a not fully statistically relevant extent (p = 0.06). The addition of maintenance endocrine therapy (ET) to pertuzumab/trastuzumab maintenance was associated with longer PFS (p = 0.0001), although no significant differences were detected in OS (p = 0.31). Results were confirmed by propensity score analysis (p = 0.003 and p = 0.46, respectively). In multivariate models, longer PFS was related to lower Performance Status (PS) (p = 0.07), metastatic stage at diagnosis (p = 0.006) and single metastatic site (p < 0.0001). An OS advantage was observed with lower PS (p < 0.0001), single metastatic site (p = 0.004), no prior exposure to trastuzumab (p = 0.004) and response to pertuzumab-based treatment (p = 0.003). Our results confirm that trastuzumab/pertuzumab/taxane is the standard of care as first-line treatment of patients with HER2-positive ABC even in the real-world setting. Moreover, the double-maintenance therapy (HER2 block and ET) is strongly recommended when feasible.
Cancers
The approval of trastuzumab emtansine (T-DM1) was conducted without pertuzumab as previous therapy. Efficacy data on T-DM1 following pertuzumab treatment are therefore limited. This study explores this issue in a real-world setting. Within the prospective PRAEGNANT (Prospective Academic Translational Research Network for the Optimization of the Oncological Health Care Quality in the Advanced Setting) metastatic breast cancer registry (NCT02338167), patients in all therapy lines receiving any kind of treatment were eligible for inclusion. This report describes patient characteristics and progression-free survival (PFS) in human epidermal growth factor receptor 2 (HER2)-positive patients receiving T-DM1 after pertuzumab treatment. Seventy-six patients were identified, 39 of whom received T-DM1 as second-line therapy, 25 as third-line, and 12 as fourth-line therapy or higher. Pertuzumab was mostly administered as a first-line treatment (n = 61; 80.3%). The median PFS in all patients wa...
Zenodo (CERN European Organization for Nuclear Research), 2023
The aim of this study was to evaluate the efficacy of Lapatinib, trastuzumab emtansine (T-DM1) treatment after pertuzumab in patients with HER2-positive metastatic breast cancer. Materials and Methods: The study included HER2-positive breast cancer patients who were followed up and treated in Adana City Training and Research Hospital. Totally 1840 patients with a diagnosis of breast cancer in the hospital management system were evaluated, 670 patients who were determined to be metastatic were evaluated for eligibility. Thirty-one patients who received pertuzumab before T-DM1 treatment, while 34 patients who received T-DM1 before pertuzumab were included. Results: Of the 65 female patients included in the study, 59 had ductal adenocarcinoma (90.8%) and 6 had lobular adenocarcinoma (9.2%). Seventeen patients (26.2%) had bone metastases, 20 patients (30.7%) had visceral metastases, and 28 patients (43.1%) had bone and visceral metastases together. Overall survival (OS) was 23.8±3 months in those who did not receive pertuzumab before T-DM1 in the metastatic setting, while it was similar in those who received pertuzumab with 22.4±2.9 months (p=0.969). Progression-free survival (PFS) was 9.1±1.3 months in those who did not receive pertuzumab before T-DM1 in the metastatic setting, while it was significantly lower in patients who received pertuzumab with 4.9±0.8 months (p=0.005). The comparison of initiation of T-DM1 after pertuzumab as second-line therapy in the metastatic setting and its use in later therapeutic lines revealed no difference in PFS and OS (p=0.628 and p=0.706, respectively). Conclusion: Pertuzumab should be preferred primarily because it is more effective in metastatic HER2-positive breast cancer. Despite the significant decrease in PFS of patients using T-DM1 after pertuzumab, there was no decrease in OS; therefore the earlier T-DM1 therapy is initiated following pertuzumab, the more effective it is.
BMC Cancer, 2021
Background: Trastuzumab emtansine (T-DM1) is indicated as second-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic or unresectable locally advanced breast cancer, after progression on trastuzumab and a taxane-based chemotherapy. We wished to determine if the line of treatment in which T-DM1 is administered has an impact on progression-free survival (PFS) and in particular, if prior treatment with capecitabine/lapatinib or pertuzumab modifies PFS of further treatment with T-DM1. Patients and methods: We performed a multicenter retrospective study in 3 Belgian institutions. We evaluated PFS with T-DM1 in patients treated for HER2 positive metastatic or locally advanced unresectable breast cancer between
Background: The current standard first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive (þ) metastatic breast cancer is the combination of pertuzumab, trastuzumab and a taxane (P þ T þ taxane), while standard second-line is ado-trastuzumab-emtansine (T-DM1). The registration trial of pertuzumab, however, did not include earlyrelapsing patients, defined as patients experiencing tumor relapse 12 months from the end of (neo)adjuvant anti-HER2 therapy. Conversely, the pivotal trial of T-DM1 included some patients relapsing 6 months after the end of (neo)adjuvant trastuzumab. Thus, a proportion of early-relapsing patients are currently eligible to receive T-DM1 as first-line treatment. Nevertheless, no direct comparison exists between the two regimens in this clinical setting. Patients and methods: We retrospectively compared T-DM1 versus P þ T þ taxane as first-line treatment in two cohorts of early-relapsing patients in an Italian 'real-world' setting, involving 14 public health care institutions. The primary endpoint was progression-free survival. Secondary endpoints included patients' characterization, overall survival and post-progression survival. Univariate and multivariate analyses were carried out. All tests were twosided and a P 0.05 was considered statistically significant. Results: Among 1252 screened patients, 75 met the inclusion criteria. Forty-four (58.7%) received P þ T þ taxane and 31 (41.3%) received T-DM1. The two cohorts showed similar characteristics of aggressiveness and no significant differences in treatment history. T-DM1, compared with P þ T þ taxane was associated with worse progression-free survival (adjusted hazard ratio: 2.26, 95% confidence interval: 1.13-4.52, P ¼ 0.021) and overall survival (adjusted hazard ratio: 3.95, 95% confidence interval: 1.38-11.32, P ¼ 0.010), irrespective of previous (neo)adjuvant treatment, age, hormone receptors status, time-to-relapse (6 months or within 6-12 months) and presence of visceral/brain metastases. No differences were observed in post-progression survival (P ¼ 0.095). Conclusions: Our study suggests superiority for P þ T þ taxane over T-DM1 as up-front treatment of early-relapsing HER2þ metastatic breast cancer, which merits further assessment in larger and prospective trials.
Journal of Clinical Oncology, 2014
Our phase IIa study characterized the safety and efficacy of two human epidermal growth factor receptor 2 (HER2)-targeted agents, trastuzumab emtansine (T-DM1) and pertuzumab, in patients with HER2-positive metastatic breast cancer (MBC). Patients and Methods Patients with HER2-positive locally advanced breast cancer or MBC were treated with 3.6 mg/kg T-DM1 plus pertuzumab (840-mg loading dose, then 420 mg subsequently) once every 3 weeks. The primary efficacy end point was investigator-assessed objective response rate (ORR). Results Sixty-four patients (43 patients in the second-line or greater setting [advanced MBC]; 21 patients in the first-line setting [first-line MBC]) were enrolled. Patients with advanced MBC had received trastuzumab and a median of six prior nonhormonal treatments for MBC; 86% of first-line MBC patients had received trastuzumab in the (neo)adjuvant setting. The ORR was 41% overall, 33% in patients with advanced MBC, and 57% in first-line patients. Median progression-free survival was 6.6, 5.5, and 7.7 months, respectively. The most common adverse events were fatigue (61%), nausea (50%), and diarrhea (39%). The most frequent grade Ն 3 adverse events were thrombocytopenia (13%), fatigue (11%), and liver enzyme elevations (increased ALT: 9%; increased AST: 9%). One patient had left ventricular ejection fraction of less than 40% after study drug discontinuation. Exploratory biomarker analyses demonstrated that patients with above-median tumor HER2 mRNA levels had a numerically higher ORR than patients with below-median levels (44% v 33%, respectively). Conclusion T-DM1 and pertuzumab can be combined at full doses with no unexpected toxicities. The preliminary efficacy in patients in the first-line and advanced MBC settings warrants further investigation.
Cancers
Real-world studies have suggested decreased trastuzumab emtansine (T-DM1) effectiveness in patients with metastatic breast cancer (mBC) who received prior trastuzumab plus pertuzumab (H + P). However, these studies may have been biased toward pertuzumab-experienced patients with more aggressive disease. Using an electronic health record-derived database, patients diagnosed with mBC on/after 1 January 2011 who initiated T-DM1 in any treatment line (primary cohort) or who initiated second-line T-DM1 following first-line H ± P (secondary cohort) from 22 February 2013 to 31 December 2019 were included. The primary outcome was time from index date to next treatment or death (TTNT). In the primary cohort (n = 757), the percentage of patients with prior P increased from 37% to 73% across the study period, while population characteristics and treatment effectiveness measures were generally stable. Among P-experienced patients from the secondary cohort (n = 246), median time from mBC diagnos...
Annals of Oncology, 2021
Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/ mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HRnegative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.