Pharmacoeconomic analysis of a combination of capecitabine (X) with docetaxel (D) and trastuzumab (H) first-line in HER2- positive advanced or metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17036-17036
Author(s):  
A. Bonetti ◽  
A. Santoro ◽  
A. Cirrincione ◽  
G. Giuliani ◽  
R. Bell
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Data ◽  
Pharmacoeconomic Analysis ◽  
Metastatic Breast ◽  
Medical Costs ◽  
Her2 Positive ◽  
System Perspective ◽  
Direct Medical Costs ◽  
Grade 3

17036 Background: A recently published (Wardley et al ESMO 2006) randomized phase II trial (CHAT) compared XDH with DH. The primary endpoint, overall response rate, was similar with XDH (71%) and DH (73%), while XDH showed superior time to progression (TTP) (hazard ratio [HR] 0.70, p=0.045, median 18.2 vs 13.8 months, respectively) and a trend toward superior progression-free survival (HR 0.72, p=0.06, median 14.8 vs 12.8 months, respectively). Overall survival data are immature. This analysis evaluates potential pharmacoeconomic impacts of adding X to DH. Methods: Direct medical costs during the study were estimated from the Italian health system perspective. Actual doses of both regimens were modeled from trial data. Grade 3/4 adverse events (AEs) and related medications were analyzed to estimate costs of treating major AEs. Other costs relating to laboratory tests and drug administration were assumed to be the same in both arms. Results: Total direct medical costs were slightly lower for XDH: €15250 vs €15570 for DH. As expected, the main cost drivers were drug costs: €14,370 vs €14,690, respectively. XDH and DH safety profiles were different: XDH resulted in more grade 3/4 non-hematologic AEs than DH (total: 77% vs 68%; hand-foot syndrome: 16% vs <1%; diarrhea: 11% vs 4%, respectively), but less grade 3/4 neutropenia (54% vs 77%), complicated neutropenia (20% vs 24%) and febrile neutropenia (14% vs 23%). The estimated mean AE costs per patient were similar in both arms. Conclusion: With the convenience of oral therapy, adding X to DH does not increase the number and duration of infusion visits or increase costs. For patients, physicians and payers, XDH is a good alternative for the treatment of advanced/metastatic breast cancer. [Table: see text]

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: An Integrated Safety Analysis

2014 ◽  
Vol 32 (25) ◽  
pp. 2750-2757 ◽  
Author(s):  
Véronique Diéras ◽  
Nadia Harbeck ◽  
G. Thomas Budd ◽  
Joel K. Greenson ◽  
Alice E. Guardino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Grade 3

Purpose The antibody–drug conjugate trastuzumab emtansine (T-DM1) combines the cytotoxic activity of DM1 with the human epidermal growth factor receptor 2 (HER2) –targeted, antitumor properties of trastuzumab. T-DM1 has shown activity in phase I and II single-arm studies in patients with pretreated HER2-positive metastatic breast cancer (MBC) and has demonstrated superior efficacy and improved tolerability versus standard MBC treatments in randomized phase II and III studies. This analysis, combining available data from all single-agent T-DM1 studies to date, was conducted to better define the T-DM1 safety profile. Patients and Methods Six studies in patients with HER2-positive MBC who received T-DM1 3.6 mg/kg every 3 weeks and follow-up data from patients in an extension study were analyzed. Analyses included adverse events (AEs) by grade; AEs leading to death, drug discontinuation, or dose reduction; and select AEs. Results Among 884 T-DM1–exposed patients, the most commonly reported all-grade AEs were fatigue (46.4%), nausea (43.0%), thrombocytopenia (32.2%), headache (29.4%), and constipation (26.5%). The most common grade 3 to 4 AEs were the laboratory abnormalities of thrombocytopenia (11.9%) and increased AST serum concentration (4.3%). These were manageable and not generally associated with clinical symptoms. There were 12 AE-related deaths. AEs resulted in dose reductions in 17.2% of patients and drug discontinuations in 7.0%. Conclusion In this analysis of 884 T-DM1–exposed patients, grade 3 or greater AEs were infrequent and typically asymptomatic and manageable. This favorable safety profile makes T-DM1 treatment suitable for exploration in other breast cancer settings.

scholarly journals The Difference in Clinical and Prognostic Features Between De Novo and Recurrent Her2-Positive Metastatic Breast Cancer Patients

Acta Medica ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 14-19
Author(s):  
Yusuf Acikgoz ◽  
Yakup Ergun ◽  
Gokhan Ucar ◽  
Merve Dirikoc ◽  
Dogan Uncu
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Data ◽  
De Novo ◽  
Metastatic Breast ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Prognostic Features ◽  
Her 2

Abstract   BACKGROUND: There are different data in the literature about the consequences of the development of metastasis as de novo or recurrent. In this study, we retrospectively investigated the clinicopathologic and prognostic characteristics of HER-2 positive de novo and recurrent metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: The data of patients admitted to our clinic between 1996-2017 were analyzed retrospectively. The baseline features, treatments and survival data were recorded. Recurrent metastatic patients were further categorized as disease free interval (DFI) <24 months and DFI >24 months. The features of two groups were analyzed by pearson chi-square test. Survival were calculated by using the Kaplan-Meier method with the Long-rank test. p <0.05 was considered statistically significant. RESULTS: A total of 44 patients were included to study in which 20 patients in de novo HER-2 positive MBC group and 24 patients in recurrent HER-2 MBC group. There was no difference in baseline features between groups. The median OS in de novo and recurrent MBC group was 60.3 months and 43.9 months respectively (HR: 0.87, 95% CI 0.37-2.05, p=0.76). OS was not different between de novo MBC group and patients with DFI <24 months and with DFI > 24 months (p=0.135). CONCLUSION: Our study showed that baseline features of patients with de novo HER-2 positive MBC and recurrent HER-2 positive MBC did not differ from each other. The presence of metastasis at the time of diagnosis or during follow-up did not change response to treatments.  

Lapatinib with trastuzumab for heavily treated HER2-positive metastatic breast cancer (mBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11561-e11561
Author(s):  
Miguel J. Sotelo ◽  
Luis Manso ◽  
José Ángel Garcia Saenz ◽  
Eva M. Ciruelos ◽  
Fernando Moreno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Heavily Pretreated ◽  
Previously Treated ◽  
Grade 3

e11561 Background: Trastuzumab and lapatinib show complementary and non-cross resistant mechanisms of anti-HER2 action. Dual HER2 blockade has been preclinically and clinically assessed with encouraging results. Trastuzumab and lapatinib combination is effective in terms of survival in patients with heavily pretreated HER2-positive mBC. We aim to report our experience with lapatinib plus trastuzumab in this setting. Methods: Descriptive retrospective study of trastuzumab plus lapatinib activity in patients with HER2-overexpressing metastatic breast cancer treated in two institutions from 01/2007 to 12/2012. The objective of this analysis is to report the response rate (RR), progression-free survival (PFS) and toxicity. Results: 23 HER2-positive mBC patients previously treated with trastuzumab received trastuzumab plus lapatinib based therapy. 15 patients (65%) received 2 or more previous lines. 17 patients (74%) had visceral disease. Chemotherapy (CT) was added to the dual HER2 blockade treatment in 13 patients (56%) whereas hormonotherapy (HT) was added in 8 patients (35%) and 2 patients (9%) received lapatinib plus trastuzumab without any other agent. Chemotherapeutic drugs most used were: capecitabine (54%) and vinorelbine (15%). RR: partial response 22% (5/23), stable disease 39% (9/23). Median of follow-up was 11 months. PFS in the overall population was 4 months. PFS in patients with CT was 5 months, while PFS in patients with HT was only 2. PFS in hormone receptor positive and negative was 3 and 5 months respectively. The most common toxicities were: diarrhea (48%), anemia (39%), asthenia (39%) and hand-and-foot syndrome (17%). Grade ≥ 3 toxicity was diarrhea (26%) and hand-and-foot syndrome (9%). The incidence of cardiotoxicity was 9% (grade 2). Conclusions: These findings suggest that dual HER2 blockade in combination with CT is feasible and active in heavily pretreated HER2-positive mBC patients. However, further investigation is warranted to demonstrate superiority over sequential blockade with trastuzumab and lapatinib in this setting.

Phase I study of alpelisib (BYL-719) and T-DM1 in HER2-positive metastatic breast cancer after trastuzumab and taxane therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1026-1026 ◽  
Author(s):  
Sarika Jain ◽  
Cesar Augusto Santa-Maria ◽  
Alfred Rademaker ◽  
Francis J. Giles ◽  
Massimo Cristofanilli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Phase I Study ◽  
Metastatic Breast ◽  
Median Number ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Metastatic Setting ◽  
Grade 3

1026 Background: Constitutive activation of the phosphatidylinositol-3-kinase (PI3K) signaling pathway is a mechanism of trastuzumab resistance in HER2-positive metastatic breast cancer (MBC). Alpelisib (BYL-719) is the first oral PI3K inhibitor that selectively inhibits the PI3Kα isoform. We aimed to determine the maximum tolerated dose (MTD), safety, and activity of alpelisib with ado-trastuzumab emtansine (T-DM1) in HER2-positive MBC that failed standard therapy. Methods: In this phase I study, pts received alpelisib daily (cohort 1: 300 mg, (-1): 250 mg) and T-DM1 3.6 mg/m2 on Day 1 every 21 days using a 3+3 design with dose expansion at MTD. Dose-limiting toxicity (DLT) was defined as CTCAE Grade 3/4 adverse events (AE) during cycle 1. Data cut-off is Jan. 1, 2017. Results: 17 pts were enrolled. Median age was 53 (40-66). Median prior lines of therapy in metastatic setting was 4.5 (0-13) including 9 pts who progressed on prior T-DM1 (after median 8 cycles). Median number of metastatic sites was 2 (1-5). Median number of cycles per pt who completed at least 1 cycle was 8 (1-19). Five pts were enrolled in cohort 1 with 2 DLTs (grade 3 rash), leading to cohort (-)1, in which there were no DLTs. The most common alpelisib-related AEs were hyperglycemia (n = 9, 53%), fatigue (n = 9, 53%), nausea (n = 7, 35%), and rash (n = 8, 47%). Grade 3 alpelisib-related AEs included rash (n = 7), hyperglycemia (n = 3), weight loss (n = 1), hypertension (n = 2), and pancreatitis (n = 1). Grade 3 rash occurred during cycle 1, which resolved with interruption and subsequent dose reduction of alpelisib and use of steroids. Grade 3 hyperglycemia was reversible with oral anti-diabetic treatment. One Grade 4 AE occurred (thrombocytopenia) likely due to T-DM1. MTD for alpelisib was established as 250 mg daily. Median follow-up was 11.6 months (0.3-19.5). Median PFS was 6 months (95% CI 2.9-10.6). In 11 pts without prior T-DM1 mPFS was 4.3 months (95% CI 2.0-8.8) and in 6 pts with prior T-DM1 it was 10.6 months (95% CI 1.6-12.6), p = 0.18. Conclusions: The combination of alpelisib 250 mg daily and T-DM1 appears to be safe in HER2-positive MBC pts with significant anti-tumor activity, even in pts previously treated with T-DM1. A phase II study is planned. Clinical trial information: NCT02038010.

Study of lapatinib (T) in combination with trastuzumab (T) in women heavily pretreated with HER2-positive metastatic breast cancer (MBC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11577-e11577 ◽  
Author(s):  
Javier Salvador ◽  
Manuel Ruiz Borrego ◽  
Maria Valero ◽  
Juan L. Bayo ◽  
Luis De La Cruz-Merino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Benefit ◽  
Kinase Inhibitor ◽  
Antitumour Activity ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Heavily Pretreated ◽  
Grade 3

e11577 Background: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer.In heavily pre-treated pts, L+T is associated with improved outcomes compared to L alone and significantly improved progression-free survival (PFS), offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor. (Kimberly L et al, 2012 JCO). Methods: We evaluated the safety and efficacy of L+T in patients with 1-4 prior (Median 3) lines of chemotherapy (CT) for HER2+ MBC.: 20 Pts with measurable, HER2+ MBC were eligible. Pts received every 3 weeks T (8 mg/kg loading then 6 mg/Kg) and daily L 1000 mg. Results: The characteristic of the all of pts included (20) are: median age 51.4 (32-68) Total number of cycles administered was 141. The median cycles administered per pts was 6 (range 1-18). Median follow-up was 6 months. Of the 18 pts with response assessment, the clinical benefit obtained was: 76,1% (5,9% PR + and 70,6% disease stabilization) with 95% CI 71.3%-80.9%. Disease progression was 17,6%. Of the 20 pts with a median follow up of 13,32 m (3-32), median PFS for these pts was 6 m. The one year OS % was 64,70% (56,7-72,7). All pts had received al least one line lapatinib prior (1-3). Toxicity was generally manageable. No major cardiac dysfunctions ocurred. Grade 3/4 treatment-related toxicities were uncommon (grade 3 diarrhea, 18%; grade 3 hepatic 7%. All others < 3 %). Conclusions: L+T is an active regimen in HER2+ MBC. L+T showed high clinical benefit with manageable safety profile. Dual inhibition of HER2 might be a valid approach to treatment of Her-2 positive metastatic breast cancer.

Infusional Paclitaxel and Weekly Vinorelbine Chemotherapy With Concurrent Filgrastim for Metastatic Breast Cancer: High Complete Response Rate in a Phase I-II Study of Doxorubicin-Treated Patients

1999 ◽  
Vol 17 (5) ◽  
pp. 1407-1407 ◽  
Author(s):  
Georgiana K. Ellis ◽  
Julie R. Gralow ◽  
H. Irving Pierce ◽  
Margaret A. Williams ◽  
R. B. Livingston
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Data ◽  
Response Rate ◽  
Metastatic Breast ◽  
Complete Response ◽  
First Line Therapy ◽  
Nonrandomized Trial ◽  
Pretreated Patients ◽  
Grade 3

PURPOSE: We investigated 96-hour paclitaxel infusion combined with weekly (days eight and 15) vinorelbine as salvage therapy for metastatic breast cancer in anthracycline-exposed patients. All patients received scheduled support with granulocyte colony-stimulating factor (G-CSF; filgrastim). Tumor response, toxicity, time to progression (TTP), and survival were assessed. PATIENTS AND METHODS: This single-center nonrandomized trial enrolled 32 patients. Anthracycline exposure and subsequent progression were common to all patients. Paclitaxel and vinorelbine were escalated over three dosing levels, stratified by liver function. RESULTS: Seven patients (22%) achieved a complete response and nine patients achieved a partial response for an overall response rate of 50%. The median TTP was 6.1 months, and median survival time was 14.1 months. Dose-limiting toxicity was neutropenia, with dose delay or reduction in seven of 32 patients. Febrile neutropenia requiring hospitalization was uncommon (three of 32 patients; 9%). There were no treatment-related deaths. Grade 3/4 thrombocytopenia occurred in two patients (6%), and 13 patients (41%) required RBC transfusions for anemia. Grade 3 nausea and vomiting was seen in one patient, who was found to be Addisonian. Despite potentially overlapping neurologic toxicities of the two agents, only two patients (6%) were removed from the study because of progressive peripheral neuropathy. CONCLUSION: Administration of 96-hour paclitaxel infusion and subsequent weekly vinorelbine with G-CSF support is well tolerated. The response rate, TTP, and survival data are encouraging for therapy given to anthracycline pretreated patients with metastatic breast cancer. If these results can be verified in multi-institution trials, this or a similar combination of drugs would merit investigation as first-line therapy in this patient population.

Phase I Study and Biomarker Analysis of Pyrotinib, a Novel Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

2017 ◽  
Vol 35 (27) ◽  
pp. 3105-3112 ◽  
Author(s):  
Fei Ma ◽  
Qiao Li ◽  
Shanshan Chen ◽  
Wenjie Zhu ◽  
Ying Fan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Antitumor Activity ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Maximum Tolerated Dose ◽  
Circulating Tumor Dna ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Grade 3

Purpose This phase I study assessed the safety, tolerability, pharmacokinetics, antitumor activity, and predictive biomarkers of pyrotinib, an irreversible pan-ErbB inhibitor, in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer. Patients and Methods Pyrotinib was administered continuously, orally, once per day to patients who did not have prior exposure to tyrosine kinase inhibitors of HER2. Planned dose escalation was 80, 160, 240, 320, 400, and 480 mg. For pharmacokinetic analysis, timed blood samples were collected on day 1 and day 28. Next-generation sequencing was performed on circulating tumor DNA and genomic DNA from tumor samples. Results Thirty-eight patients were enrolled. The dose-limiting toxicity was grade 3 diarrhea, which occurred in two patients administered 480 mg of pyrotinib; thus, the maximum tolerated dose was 400 mg. Common pyrotinib-related adverse events included diarrhea (44.7% [17 of 38]), nausea (13.2% [five of 38]), oral ulceration (13.2% [five of 38]), asthenia (10.5% [four of 38]), and leukopenia (10.5% [four of 38]). The only grade 3 adverse event was diarrhea. Pharmacokinetic analyses indicated that pyrotinib exposure was dose dependent. The overall response rate was 50.0% (18 of 36), and the clinical benefit rate (complete response + partial response + stable disease ≥ 24 weeks) was 61.1% (22 of 36). The median progression-free survival was 35.4 weeks (95% CI, 23.3 to 40.0 weeks). The overall response rate was 83.3% (10 of 12) in trastuzumab-naive patients and 33.3% (eight of 24) in trastuzumab-pretreated patients. Preliminary results suggest that PIK3CA and TP53 mutations in circulating tumor DNA ( P = .013) rather than in archival tumor tissues ( P = .474) may predict the efficacy of pyrotinib. Conclusion Continuous once-per-day pyrotinib was well tolerated and demonstrated promising antitumor activity in HER2-positive patients with metastatic breast cancer. The maximum tolerated dose was established as 400 mg. Diarrhea was the dose-limiting toxicity. The promising antitumor activity and acceptable tolerability of pyrotinib warrant its further evaluation in a phase II study.

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