scholarly journals A Retrospective Analysis of the Effect of Irinotecan-Based Regimens in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiaojiao Suo ◽  
Xiaorong Zhong ◽  
Ping He ◽  
Hong Zheng ◽  
Tinglun Tian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Data ◽  
Univariate Analysis ◽  
Objective Response ◽  
Metastatic Breast ◽  
Visceral Metastasis ◽  
Metastatic Setting ◽  
Previously Treated ◽  
Third Line

BackgroundAt present, patients with metastatic breast cancer (MBC) have few treatment options after receiving anthracyclines and taxanes. Studies have shown that irinotecan has modest systemic activity in some patients previously treated with anthracyclines and taxanes. This study aimed to evaluate the efficacy of irinotecan-based chemotherapy for breast cancer patients in a metastatic setting.MethodsWe retrospectively collected the clinical information and survival data of 51 patients with MBC who received irinotecan at West China Hospital of Sichuan University. The primary endpoints were the progression free survival (PFS) and overall survival (OS), and the secondary endpoint was the objective response rate (ORR). To minimize potential confounding factors, we matched 51 patients who received third-line chemotherapy without irinotecan through propensity score matching (PSM) based on age, hormone receptor (HR), and human epidermal growth factor receptor 2 (HER2), compared their OS and PFS rates to those treated with irinotecan.ResultsFrom July 2012 to October 2020, 51 patients were treated with an irinotecan-containing regimen. The median number of previous treatment lines was 4, and a median of two previous chemotherapy cycles (ranging from 1–14 cycles) were given in a salvage line setting. The ORR was 15.7%, and the disease control rate (DCR) was 37.3%. For the irinotecan group, the median PFS was 3.2 months (95% CI 2.7–3.7), while the median OS was 33.1 months (95% CI 27.9–38.3). Univariate analysis results suggested that irinotecan could improve PFS in patients with visceral metastasis (P=0.031), which was 0.7 months longer than patients without visceral metastasis (3.5 months vs. 2.8 months). Compared to the patients who received third-line non-irinotecan chemotherapy, the irinotecan group showed a longer trend of PFS without statistical significance (3.2 months vs 2.1 months, P = 0.052). Similarly, the OS of the irinotecan group was longer than the third-line survival without irinotecan, but it was not statistically significant (33.1 months vs 18.0 months, P = 0.072).ConclusionsFor MBC patients who were previously treated with anthracyclines and/or taxanes, an irinotecan-containing regimen achieved moderate objective response and showed a trend of survival benefit, which deserves further study.

Final analysis of phase II study of EZN-2208 (PEG-SN38) in metastatic breast cancer (MBC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1017-1017 ◽  
Author(s):  
Cynthia R. C. Osborne ◽  
Joyce O'Shaughnessy ◽  
Frankie Ann Holmes ◽  
Hyun Sue Kim ◽  
Darren M. Kocs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Benefit ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Final Analysis ◽  
Water Soluble ◽  
Prolonged Release ◽  
Previously Treated

1017 Background: EZN-2208 is a water-soluble PEGylated conjugate of SN38. EZN-2208 results in prolonged exposure of tumors to SN38 via preferential accumulation of EZN-2208 in the tumor and prolonged release of SN38. These data represent the final analysis of our study evaluating EZN-2208 in MBC. Methods: EZN-2208 9 mg/m2 (SN38 equivalents) was delivered as a 60-minute IV infusion, weekly for 3 wks in 4‑wk cycles. The primary objective was to determine the overall response rate (RR) in female patients with metastatic breast cancer (MBC) who had received prior adjuvant or metastatic therapy with either 1) anthracycline and taxane (AT) or 2) anthracycline, taxane, and capecitabine (ATX). Secondary objectives included evaluation of RR based on tumor receptor status, duration of response, progression-free survival (PFS), overall survival (OS), and safety. Results: Patients with MBC (n=164) were treated with a median (range) of 3.3 (0.3-22) cycles of EZN-2208. The objective response rate (RR) was 20% for AT and 9% for ATX. The clinical benefit rate (CBR=%CR + %PR + %SD ≥6 months) was 41% and 27% in patients in the AT and ATX cohorts, respectively. The RR and CBR among ER+ patients were 11% (10/91 pts) and 41.8% (38/91 pts). In patients who progressed during or within 30 days of prior platinum-containing regimens (Platinum Progressors), the CBR was 20% (8/40 pts). Among triple negative breast cancer (TNBC) patients, the RR and CBR were 22.5% (11/49 pts) and 36.7% (18/49 pts). For TNBC, Platinum Progressors, the CBR was 26.1% (6/23 pts). Overall, most common reported drug-related adverse events were diarrhea, nausea and neutropenia. Conclusions: EZN-2208 has notable activity in patients with previously treated MBC and appears to be an active agent for treatment of TNBC. Patients with TNBC, who had been previously treated with a platinum-based regimen, also derive clinical benefit from EZN-2208. The safety profile of EZN-2208 is acceptable with good tolerability in most patients. Further evaluation of EZN-2208 in MBC in general and TNBC in particular is warranted.

Trastuzumab deruxtecan for HER2+ advanced breast cancer

2021 ◽  
Author(s):  
Jiyun Lee ◽  
Yeon Hee Park
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancer Patients ◽  
Antibody Drug Conjugate ◽  
Metastatic Setting ◽  
Clinical Benefits

Trastuzumab deruxtecan (T-DXd, DS-8201), an anti-HER2 antibody–drug conjugate, has shown significant clinical benefits in HER2+ metastatic breast cancer patients. In the phase 2 DESTINY-Breast01 trial, T-DXd demonstrated an objective response of 60.9% and median progression-free survival of 16.4 months, laying the foundation for accelerated approval in HER2+ metastatic breast cancer patients who have received two or more prior anti-HER2-based regimens in the metastatic setting. Moreover, T-DXd exhibited promising antitumor efficacy against HER2-low-expressing metastatic breast cancer. Its distinctive side effect was pneumonitis, with a 13.6% incidence. It is approved in the US with boxed warnings for interstitial lung disease and embryo–fetal toxicity. This review focuses on preclinical, pharmacokinetic and pharmacodynamic data on T-DXd and clinical evidence of its antitumor activity (both as monotherapy and in combination) and tolerability in metastatic breast cancer.

Chemotherapy with Mitomycin C and Vinblastine in Pretreated Metastatic Breast Cancer

1993 ◽  
Vol 79 (4) ◽  
pp. 254-257 ◽  
Author(s):  
Francesco Perrone ◽  
Sabino De Placido ◽  
Chiara Carlomagno ◽  
Francesco Nuzzo ◽  
Angela Ruggiero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Mitomycin C ◽  
Site Response ◽  
Objective Response ◽  
Metastatic Breast ◽  
Median Number ◽  
Breast Cancer Patients ◽  
Metastatic Site ◽  
Third Line

Aims In February 1986 we began a study to test the activity of mitomycin C (12 mg/m2) plus vinblastine (6 mg/m2) on day 1 of a 28-day cycle (MV) as second or third-line chemotherapy for metastatic breast cancer patients. Methods As of February 1988 the study was stopped after 26 patients had been enrolled. The median age of the patients was 54 years (range 35-78); all patients were progressive from chemotherapy; 15 (57.7 %) patients were treated as second and 11 (42.3 %) as third line; 19 (73.1 %) patients had received anthracyclines as first (13 patients) or second-line (6 patients) chemotherapy; 18 (69.2 %) patients had visceral Involvement; 7 (26.9 %) had one metastatic site, 11 (42.3 %) two sites, 6 (23.1 %) three sites and 2 (7.7 %) four sites. Results Overall, 86 cycles were administered, with a median number of 3 cycles per patient. Toxicity was mild; hematologic side effects required discontinuation of treatment in 3 cases. Vomiting occurred in 3 (11.5 %) patients, nausea in 5 (19.2 %). Moderate neurologic toxicity was recorded in 6 (23 %) patients. No complete and 3 partial responses were observed. The objective response rate was 11.5 % (exact 95 % confidence interval, 2.4-30.1). Responses occurred independently of disease-free interval, dominant metastatic site, response to previous chemotherapy, previous anthracycline and line of treatment; all responses were recorded in patients under 50 years of age. Kaplan-Meier estimated median time to progression and overall survival were 13 and 40 weeks, respectively. Conclusion The MV regimen was well tolerated but showed little activity in pretreated metastatic breast cancer.

Fluorouracil and high-dose leucovorin in previously treated patients with metastatic breast cancer.

1989 ◽  
Vol 7 (7) ◽  
pp. 890-899 ◽  
Author(s):  
S M Swain ◽  
M E Lippman ◽  
E F Egan ◽  
J C Drake ◽  
S M Steinberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Metastatic Breast ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Tumor Biopsy ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

The efficacy and toxicity of leucovorin 500 mg/m2 administered intravenously (IV) over 30 minutes daily for five days followed in one hour by fluorouracil (5-FU) 375 mg/m2 administered IV daily for five days, each given every 3 weeks, was assessed in 54 previously treated patients with metastatic breast cancer. An overall objective response rate of 24% was achieved (95% confidence interval, 13% to 38%), with an additional 56% of patients maintaining stable disease. Eleven of 12 patients who responded had received previous 5-FU therapy. Toxicity of this regimen included grade 3 diarrhea in 13%, grade 3 or 4 mucositis in 33%, grade 3 or 4 granulocytopenia in 65%, and grade 3 or 4 thrombocytopenia in 19%. Delay of treatment was required for hematologic toxicity in 44 patients. Thirty-eight patients required dose reductions due to toxicity. Biochemical evaluation of tumor biopsy specimens obtained from 17 patients used as their own controls with and without leucovorin was performed. These studies reveal an increased stabilization of the 5-fluorodeoxyuridylate (FdUMP)-thymidylate synthase (TS) folate ternary complex with the addition of leucovorin. There was a 71% +/- 14% occupancy or inhibition of the enzyme with the use of both 5-FU and leucovorin, v 30% +/- 13% for 5-FU alone (P2 less than .037). The percent TS bound in responding patients was substantially higher than in those patients with progressive disease. Finally, the mean total tumor TS pre-therapy in seven patients was 31 fmol/mg compared with a mean of 81 fmol/mg in these same seven patients 24 hours after therapy. This 2.6-fold increase suggests that there is an induction of the enzyme, TS, with 5-FU treatment.

A phase 2 study of napabucasin with weekly paclitaxel in previously treated metastatic breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1084-1084 ◽  
Author(s):  
William Jeffery Edenfield ◽  
Carlos Becerra ◽  
Adrian Langleben ◽  
Alexander I. Spira ◽  
Fadi S. Braiteh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Triple Negative ◽  
Objective Response ◽  
Metastatic Breast ◽  
Weekly Paclitaxel ◽  
Prior History ◽  
Combination Regimen ◽  
Dose Escalation Study ◽  
Previously Treated

1084 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Napabucasin has shown potent synergistic preclinical anti-tumor activity with paclitaxel (PTX). In a phase Ib dose escalation study in patients (pts) with advanced solid tumors, Napabucasin plus weekly paclitaxel was well tolerated. A phase II expansion cohort was opened for pts with previously treated metastatic breast cancer (MBC). Methods: Pts with metastatic MBC for whom weekly PTX was a reasonable treatment option received Napabucasin 240, 480, or 500 mg orally, twice daily in combination with paclitaxel 80 mg/m2 IV weekly on 3 of every 4 weeks. Adverse events were evaluated using CTCAE v4.03 and objective tumor assessments were obtained every 8 weeks per RECIST 1.1 criteria. Results: A total of 50 pts were enrolled including 34 with triple-negative disease (negative for estrogen receptor [ER], progesterone receptor [PR], and Her2 and no prior history of positive receptor status). There were 9 pts positive for ER, PR, or Her2 and refractory to targeted agents, and 7 pts with conversion to triple-negative disease from pathology previously positive for ER, PR or Her2. Pts were heavily pre-treated, having received a median of 5 prior lines of systemic therapy. All but 3 patients had received previous systemic treatment with a taxane. Napabucasin + PTX was well tolerated. Grade 3 AE occurring in ≥ 5% patients was diarrhea (n = 4), and 1 pt had grade 4 diarrhea. The objective response rate (ORR), disease control rate (DCR), median progression free survival (mPFS), and median overall survival (mOS) for all pts and for each sub-group are summarized in the table. Conclusions: Napabucasin (BBI-608) plus weekly paclitaxel has demonstrated safety, tolerability, and encouraging signs of anti-cancer activity in pts with pretreated metastatic breast cancer. Further clinical evaluation of this combination regimen in controlled trials is warranted. Clinical trial information: NCT01325441. [Table: see text]

Phase II Clinical Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, As First-Line Therapy in Patients With Metastatic Breast Cancer Previously Treated With Anthracycline Chemotherapy

2007 ◽  
Vol 25 (23) ◽  
pp. 3415-3420 ◽  
Author(s):  
Henri Roché ◽  
Louise Yelle ◽  
Francesco Cognetti ◽  
Louis Mauriac ◽  
Craig Bunnell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Time ◽  
Objective Response ◽  
Metastatic Breast ◽  
First Line ◽  
Epothilone B ◽  
First Line Therapy ◽  
Duration Of Response ◽  
Previously Treated

PurposeThere is a need for new agents to treat metastatic breast cancer (MBC) in patients for whom anthracycline therapy has failed or is contraindicated. This study was conducted to assess the efficacy and safety of the novel antineoplastic, the epothilone B analog ixabepilone, in patients with MBC previously treated with an adjuvant anthracycline.Patients and MethodsPatients were age ≥ 18 years and had received a prior anthracycline-based regimen as adjuvant treatment. Ixabepilone as first-line metastatic chemotherapy was administered as a 40 mg/m2intravenous infusion during 3 hours every 3 weeks. The primary efficacy end point was objective response rate (ORR). Secondary efficacy end points included duration of response, time to response, time to progression, and survival.ResultsAll 65 patients were assessable for response. Their median age was 52 years (range, 33 to 80 years). ORR was 41.5% (95% CI, 29.4% to 54.4%), median duration of response was 8.2 months (95% CI, 5.7 to 10.2 months), and median time to response was 6 weeks (range, 5 to 17 weeks). Median survival was 22.0 months (95% CI, 15.6 to 27.0 months). Treatment-related adverse events were manageable and mostly grades 1/2: the most common of these (other than alopecia) was mild to moderate neuropathy, which was primarily sensory and mostly reversible in nature.ConclusionIxabepilone is efficacious and has a predictable and manageable safety profile in women with MBC previously treated with an adjuvant anthracycline.

Multicenter, Phase II Trial of Exemestane as Third-Line Hormonal Therapy of Postmenopausal Women With Metastatic Breast Cancer

1999 ◽  
Vol 17 (11) ◽  
pp. 3418-3425 ◽  
Author(s):  
S. Jones ◽  
C. Vogel ◽  
A. Arkhipov ◽  
L. Fehrenbacher ◽  
P. Eisenberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Postmenopausal Women ◽  
Hormonal Therapy ◽  
Objective Response ◽  
Metastatic Breast ◽  
Signs And Symptoms ◽  
Third Line ◽  
The Impact

PURPOSE: To assess the antitumor activity, safety, and hormone-suppressive effects of the irreversible aromatase inactivator, exemestane (Aromasin, Pharmacia & Upjohn, Kalamazoo, MI), administered as third-line hormone therapy to postmenopausal women with metastatic breast cancer that is refractory to tamoxifen and megestrol acetate. PATIENTS AND METHODS: Exemestane was administered at a dose of 25 mg/d orally until patients experienced disease progression. The efficacy and safety of exemestane were clinically and radiographically evaluated. The impact of exemestane treatment on tumor-related signs and symptoms was assessed. The effect of exemestane on serum levels of estrogens and other steroidal hormones was determined. RESULTS: Ninety-one patients were treated. There were four complete responses (CR) and eight partial responses (PR), for an objective response rate of 13% in the entire treated population. The overall success rate (CR, PR, or stable disease [SD] ≥ 24 weeks) was 30%. The median duration of response and overall success was 9 months and 8 months, respectively. Most patients with CR/PR (83%; 10 of 12 patients) and SD ≥ 24 weeks (80%; 12 of 15 patients) had improved or stable tumor-related signs and symptoms. Mean levels of circulating estrone (E1), estradiol (E2), and estrone sulfate decreased to 11%, 22%, and 13% of baseline levels, respectively (at week 8 or 16 of treatment). One half of the patients had undetectable E1 and E2 levels during treatment, including at the time of disease progression. Mild nausea (20% of patients) and hot flashes (20%) were the most common drug-related adverse events and were generally grade 1. CONCLUSION: Exemestane is an active and well-tolerated third-line hormonal therapy that represents a new treatment option for postmenopausal patients with advanced breast cancer that has become refractory to standard first- and second-line hormonal therapies.

Safety and efficacy of gemcitabine and trastuzumab in HER2-directed therapy pretreated patients with HER2-positive metastatic breast cancer: SBP-01 study.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 142-142
Author(s):  
Seiji Yoshitomi ◽  
Hisashi Tsuji ◽  
Masahiko Ikeda ◽  
Mitsuya Ito ◽  
Shoichiro Ohtani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancer Cell Lines ◽  
Her2 Positive ◽  
Disease Response ◽  
Previously Treated ◽  
Positive Breast Cancer Cell

142 Background: Prognosis of HER2-positive metastatic breast cancer (MBC) has been dramatically improved by trastuzumab (Tmab). More recently, newer anti-HER2 agents such as lapatinib, pertuzumab and T-DM1 have prolonged survival. Despite the efficacy of these drugs, most patients develop progressive disease during or after treatment, and alternative anti-HER2 agents plus chemotherapies are required in subsequent lines of treatment. However, there are few evidence on efficacy of Tmab-containing regimens after disease progression. Gemcitabine (GEM) is non-cross resistant to anthracycline and taxane. Preclinical studies have shown that the combination of Tmab and GEM has synergistic effect against HER2-positive breast cancer cell lines. SBP-01 study assessed the efficacy and safety of the combination of Tamb and GEM in patients with HER2-positive MBC previously treated with anti-HER2 therapy. Methods: SBP-01 study included patients treated with one or more anti-HER2 directed regimens for MBC. Patients were administered with GEM 1250 mg/m2 on days 1 and 8 of each 21-day cycle and Tmab 4mg/kg loading dose and then 2mg/kg weekly. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression free survival (PFS), overall survival, and safety. Results: Between June 2011 and June 2014, 35 patients were enrolled. Patients had ER positive tumor (37.1%), a median of 2 metastatic organ sites, visceral metastasis (80.0%), prior (neo) adjuvant Tmab (22.9%) and a median of 2 prior chemotherapy regimens for MBC. Previous HER2-directed drugs included Tmab (94.3%), lapatinib (37.1%), T-DM1 (8.6%) and pertuzumab (2.9%). ORR was 22.9% (95% CI, 8.6%-36.8%). Median PFS was 146 days. Patients with stable disease response received a median of 7 cycles (6-28 cycles) of treatment. Grade3/4 leukopenia (20.0%) and neutropenia (48.6%) were observed. All non-hematological toxicities were less than grade3. Conclusions: The Combination Tmab and GEM is effective and well-tolerated regimen for patients previously treated with HER2-directed therapy, and appears to make disease stable for long time period. Clinical trial information: UMIN000005881.

Safety and antitumor activity of weekly carboplatin plus paclitaxel in metastatic breast cancer: A ten years, single-institution, retrospective analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12556-e12556
Author(s):  
Claudio Vernieri ◽  
Monica Milano ◽  
Alessia Mennitto ◽  
Claudia Maggi ◽  
Benvenuto Ferrari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Retrospective Analysis ◽  
Selection Criteria ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Consecutive Series ◽  
Metastatic Setting

e12556 Background: Safety and activity of weekly carboplatin plus paclitaxel in patients (pts) with metastatic breast cancer (mBC) are poorly known. Nevertheless, taxane-based chemotherapy (ChT) is the milestone in mBC treatment. In this retrospective analysis, we report the safety and clinical activity of this combination in a consecutive series of pts treated at IRCCS Fondazione Istituto Nazionale dei Tumori in Milan in the last decade. Methods: We collecteddata on mBC patients treated between January 2007 and December 2016 with carboplatin AUC 2 plus paclitaxel 80 mg/m2on days 1 and 8, every three weeks. Selection criteria were: ECOG 0-1; evaluable and/or measurable mBC; known estrogen and progesterone receptors (ER/PgR) status and HER2 expression levels. 274 pts fulfilled the selection criteria, and 265 pts were evaluable for response and survival. Response was assessed according to RECIST criteria. Results: The median number of administered cycles was 6 (range 1-17). 66.4% and 88.3% of pts had received taxanes or antracyclines, respectively, as an adjuvant treatment or in the metastatic setting. 97% of HER2+ pts received trastuzumab concomitant with ChT. Among patients with ER/PgR-positive tumors, 42.8% received different endocrine treatments as maintenance therapy after achieving the best response with ChT or due inacceptable toxicity. Hematological and gastrointestinal toxicities were the most frequent adverse events (AEs), and were severe in 19% and 1.2% of pts, respectively. In particular, G3-G4 neutropenia and febrile neutropenia occurred in 16.8 % and 1.9 % of pts, respectively. 10.2% of pts discontinued the treatment because of toxicity. The objective response rate was 44.8% in the overall population, with median progression free survival (mPFS) of 8.6 months and median overall survival (mOS) of 23.7 months. Conclusions: Weekly carboplatin plus paclitaxel is a well-tolerated and active regimen across all different molecular subgroups of mBC. [Table: see text]

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