Human epidermal growth factor receptor 2 (HER2) suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (HALT: LPT112515).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS664-TPS664
Author(s):  
Nancy U. Lin ◽  
Michael A. Danso ◽  
Alice K. David ◽  
Joseph J. Muscato ◽  
Daniel Rayson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Objective Response ◽  
The United States ◽  
Phase Iii ◽  
Tolerability Profile ◽  
Type I ◽  
Preoperative Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Her2 Breast Cancer

TPS664 Background: Evidence supports the concept of dual HER2 blockade as a treatment strategy for HER2+ breast cancer (BC). In patients with prior trastuzumab (T)-treated HER2+ metastatic BC (MBC), treatment with T plus lapatinib (L) was associated with longer progression-free survival (PFS) and overall survival (OS) compared with L alone, and had an acceptable safety and tolerability profile. In patients with stage II/III BC, preoperative treatment with T plus L plus paclitaxel (P) resulted in significantly higher pathologic complete response rates compared with P combined with either agent alone. This study is designed to evaluate whether the addition of L improves PFS among women with HER2+ MBC receiving T as maintenance therapy. Methods: In this open-label, Phase III study, 280 patients will be stratified by line of treatment (first/second) and hormone receptor status (positive/negative), then randomized 1:1 to receive maintenance treatment with either L (1000 mg qd, continuously) in combination with T (6 mg/kg once every 3 weeks [q3w]), or T (6 mg/kg q3w) alone until disease progression, death, discontinuation due to adverse events, or other reasons. The primary endpoint is PFS; secondary endpoints are OS, clinical benefit rate, and safety. Eligible patients are females, aged ≥18 years with HER2+ MBC who have completed 12-24 weeks of first-/second-line treatment with T plus chemotherapy with an objective response or stable disease at chemotherapy discontinuation. Patients with stable brain metastases are eligible if entering the study on second-line treatment. Efficacy endpoints will be analyzed in the intent-to-treat population. A total of 193 PFS events is required to detect a 50% increase in median PFS from 18 weeks (T alone) to 27 weeks (L+T) with an associated hazard ratio of 0.667, an 80% power and a 1-sided type I error of 0.025. One interim analysis is planned for futility when ~97 PFS events (50% of required events) have been observed. Safety endpoints will be analyzed in all randomized patients who receive ≥1 dose of study medication. The trial is currently open for accrual in the United States and Canada. Clinical trial information: NCT00968968.

HALT MBC: HER2 suppression with the addition of lapatinib to trastuzumab in HER2-positive metastatic breast cancer (LPT112515).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS658-TPS658
Author(s):  
Nancy U. Lin ◽  
Michael A. Danso ◽  
Alice K. David ◽  
Joseph J. Muscato ◽  
Daniel Rayson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Objective Response ◽  
Pathologic Complete Response ◽  
The United States ◽  
Phase Iii ◽  
Type I ◽  
Preoperative Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Her2 Positive

TPS658 Background: Dual blockade of HER2 with the combination of trastuzumab (T) and lapatinib (L) enhances antitumor activity in HER2-positive breast cancer (BC) preclinical models due to the complementary mechanisms of action of the 2 agents. In patients (pts) with T-treated HER2-positive metastatic BC (MBC), treatment with the combination was associated with longer progression-free (PFS) and overall survival (OS) compared with L alone. In pts with stage II/III BC, preoperative treatment with the combination plus paclitaxel (P) resulted in significantly higher pathologic complete response rates compared with P combined with either agent alone. This evidence supports the concept of dual HER2 blockade as a treatment strategy for HER2-positive MBC. The present study is designed to evaluate whether the addition of L improves PFS among women with HER2-positive MBC receiving T as maintenance therapy. Methods: In this open-label, Phase III study, 280 pts will be stratified by line of treatment (first/second) and hormone receptor status (positive/negative), then randomized 1:1 to receive maintenance treatment with either L (1000 mg qd, continuously) in combination with T (6 mg/kg once every 3 weeks [q3w]) or T (6 mg/kg q3w) alone. Pts will receive study treatment until disease progression, death, discontinuation due to adverse events, or other reasons. The primary endpoint is PFS; secondary endpoints are OS, clinical benefit rate, and safety. Key eligibility criteria include pts with HER2-positive MBC who have completed 12 to 24 weeks of first- or second-line treatment with T plus chemotherapy with an objective response or stable disease at time of chemotherapy discontinuation. Pts with stable brain metastases are eligible if entering the study on second-line treatment. Efficacy endpoints will be analyzed in the ITT population. A total of 193 PFS events is required to detect a 50% increase in median PFS (hazard ratio=0.67) for L plus T compared with T alone (median PFS 27 vs 18 weeks, respectively). The hypothesis will be tested using a 1-sided test with 80% power and a type I error of 0.025. The trial is currently open for accrual in the United States and Canada.

Aromatase Inhibitors in the Treatment and Prevention of Breast Cancer

2001 ◽  
Vol 19 (3) ◽  
pp. 881-894 ◽  
Author(s):  
Paul E. Goss ◽  
Kathrin Strasser
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Clinical Status ◽  
Phase Iii ◽  
Type I ◽  
Third Generation ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
The Third

PURPOSE: The purpose of this article is to provide an overview of the current clinical status and possible future applications of aromatase inhibitors in breast cancer. METHODS: A review of the literature on the third-generation aromatase inhibitors was conducted. Some data that have been presented but not published are included. In addition, the designs of ongoing trials with aromatase inhibitors are outlined and the implications of possible results discussed. RESULTS: All of the third-generation oral aromatase inhibitors—letrozole, anastrozole, and vorozole (nonsteroidal, type II) and exemestane (steroidal, type I)—have now been tested in phase III trials as second-line treatment of postmenopausal hormone-dependent breast cancer. They have shown clear superiority compared with the conventional therapies and are therefore considered established second-line hormonal agents. Currently, they are being tested as first-line therapy in the metastatic, adjuvant, and neoadjuvant settings. Preliminary results suggest that the inhibitors might displace tamoxifen as first-line treatment, but further studies are needed to determine this. CONCLUSION: The role of aromatase inhibitors in premenopausal breast cancer and in combination with chemotherapy and other anticancer treatments are areas of future exploration. The ongoing adjuvant trials will provide important data on the long-term safety of aromatase inhibitors, which will help to determine their suitability for use as chemopreventives in healthy women at risk of developing breast cancer.

RIBBON-2: A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy for Second-Line Treatment of Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer

2011 ◽  
Vol 29 (32) ◽  
pp. 4286-4293 ◽  
Author(s):  
Adam M. Brufsky ◽  
Sara Hurvitz ◽  
Edith Perez ◽  
Raji Swamy ◽  
Vicente Valero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Epidermal Growth

Purpose This phase III study compared the efficacy and safety of bevacizumab combined with standard chemotherapy regimens versus chemotherapy alone as second-line treatment of patients with human epidermal growth factor receptor 2 (HER2) –negative metastatic breast cancer. Patients and Methods Patients were randomly assigned 2:1 to chemotherapy + bevacizumab or to chemotherapy + placebo. Before random assignment, investigators chose capecitabine, a taxane (paclitaxel, nab-paclitaxel, or docetaxel), gemcitabine, or vinorelbine. Dosing for bevacizumab or placebo was 15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks, depending on chemotherapy regimen. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, PFS by chemotherapy cohort, objective response rate (ORR), duration of objective response, 1-year survival rate, and safety. Results RIBBON-2 enrolled 684 patients (225, chemotherapy + placebo; 459, chemotherapy + bevacizumab). The combination of bevacizumab with chemotherapy demonstrated a statistically significant benefit. Median PFS increased from 5.1 to 7.2 months (stratified hazard ratio for PFS, 0.78; 95% CI, 0.64 to 0.93; P = .0072). The 10% improvement in ORR between the placebo- and bevacizumab-containing arms (39.5% v 29.6%; P = .0193), although not statistically significant, was consistent with previous trials. There was no statistically significant difference in overall survival. The most common grade ≥ 3 adverse events (AEs) related to bevacizumab treatment were hypertension (9.0%) and proteinuria (3.1%). There was an increased number of AEs leading to study discontinuation in the chemotherapy + bevacizumab arm compared with the chemotherapy + placebo arm (13.3% v 7.2%). Conclusion The combination of bevacizumab with commonly used chemotherapies improved PFS in the second-line treatment of patients with HER2-negative metastatic breast cancer, with a safety profile comparable with that in prior phase III studies.

A phase II trial combining tumor-targeting TP53 gene therapy with gemcitabine/nab-paclitaxel as a second-line treatment for metastatic pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4139-4139
Author(s):  
Chris Poki Leung ◽  
Minal A. Barve ◽  
Ming-Shiang Wu ◽  
Kathleen F. Pirollo ◽  
James F. Strauss ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Tp53 Gene ◽  
Phase Iii ◽  
Published Data ◽  
Line Treatment ◽  
Second Line ◽  
First Line

4139 Background: Nearly all stage IV pancreatic adenocarcinoma (PAC) patients progress after first-line treatment, and second-line options are limited. SGT-53 is an investigational product for tumor-targeted TP53 gene therapy that has completed phase Ia/Ib trials [Senser et al (2013), Mol Ther 21:1096; Pirollo et al (2016) Mol Ther 24:1697]. Methods: Here we provide an interim analysis of a Phase II trial (SGT53-02-1; NCT02340117) combining SGT-53 with gemcitabine/nab-paclitaxel (GEM/ABX). Eligible were first-line patients or those who had progressed after FOLFIRINOX (FFX) and/or gemcitabine-based therapy (second-line). In a 7-week treatment cycle, SGT-53 (3.6 mg DNA) was given once or twice weekly with GEM/ABX (1000 mg/m2/wk and 125 mg/m2/wk, respectively, for 3 of 4 weeks). Progression-free survival (PFS) and objective response rate (ORR) are primary endpoints.Overall survival (OS) and PFS are estimated by Kaplan-Meier analysis. Results: Of all evaluable patients (n=20), best response in 7 patients was determined to be partial response (PR) and 13 had stable disease (SD); none had progressive disease. In the second-line patients (n=11) there were 5 PR and 6 SD after 9 had failed FFX treatment, 3 had failed gemcitabine-based treatment and 1 had failed both. For patients with elevated CA19-9, SGT-53 + GEM/ABX resulted in marked reductions in the tumor marker. Published data for patients with PAC after therapy failure [Mita et al (2019) J Clin Med 8: 761; Portal et al (2015) Br J Cancer 113:989; Wang-Gillam et al (2016) Lancet 387:545] are shown for comparison. Notably, mPFS in our second-line patients was 7.4 months versus 3.1 months for the approved second-line therapy [Wang-Gillam et al (2016)]. This improvement in PFS exceeds the benchmark proposed to predict a clinically meaningful Phase III trial [Rahib et al (2016) Lancet Oncol 2:1209]. Conclusions: Our data suggest a clinically meaningful benefit of adding SGT-53 to GEM/ABX particularly for second-line PAC patients, most of whom had failed prior FFX treatment. Clinical trial information: NCT02340117. [Table: see text]

659 AN SINGLE-ARM OPEN-LABEL PHASE II STUDY OF CAMRELIZUMAB PLUS APATINIB AS SECOND-LINE TREATMENT FOR ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Feng Wang ◽  
Qingxia Fan ◽  
Junsheng Wang ◽  
Tao Wu ◽  
Yonggui Hong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Squamous Cell ◽  
Objective Response ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line

Abstract   Esophageal squamous cell carcinoma (ESCC) as a common malignancy is prevalent in East Asia and in eastern and southern Africa. Although pembrolizumab, nivolumab and camrelizumab are respectively recommended as second-line treatment for advanced ESCC due to improved overall survival (OS), objective response rate (ORR) was modest. New effective treatments are needed. Hence, the study of camrelizumab plus apatinib (VEGFR2 inhibitor) as second-line treatment for advanced ESCC was performed. Methods This ongoing phase II trial (NCT03736863) in six sites in China enrolled pts aged 18-75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line chemotherapy, and an ECOG performance status of 0-1. Pts received 200 mg camrelizumab intravenously every 2 weeks and apatinib 250 mg orally once per day in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and OS. Results At data cutoff (Feb 28, 2021), 52 pts were enrolled, including 42 males and 50 with distant metastases, with the median age of 62 years. In the evaluable population of 39 pts, ORR without confirmation was 43.59% and DCR was 94.87%. The median duration of response was 6.9 months (95% CI 4.57–9.23). The median PFS was 6.8 month (95% CI 2.66–10.94). The 12-month overall survival was 52.2%. A total of 80.8% of pts had treatment-related AEs (TRAEs) with 46.2% of grade ≥ 3 TRAEs. The safety profile of camrelizumab and apatinib was consistent with other anti–PD-1 antibodies and angiogenesis inhibitors. Conclusion This is the first study that evaluates the combination anti–PD-1 antibody and anti-angiogenesis inhibitor as a second-line therapy for advanced ESCC. Camrelizumab plus apatinib showed encouraging clinical efficacy and acceptable safety. Further phase III randomized trials are warranted.

Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer.

1995 ◽  
Vol 13 (11) ◽  
pp. 2722-2730 ◽  
Author(s):  
B L Weber ◽  
C Vogel ◽  
S Jones ◽  
H Harvey ◽  
L Hutchins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Breast ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

PURPOSE We evaluated single-agent intravenous (IV) vinorelbine as first- and second-line treatment for advanced breast cancer (ABC) in patients who were not resistant to anthracyclines. Objective tumor response (TR) and toxicity were assessed. PATIENTS AND METHODS A total of 107 women were enrolled onto this multicenter, nonrandomized, open-label phase II study. Patients were stratified into first- and second-line treatment groups, based on prior treatment history. Vinorelbine was initially given at 30 mg/m2/wk, with dose modification for toxicity as indicated. Therapy was continued until disease progression or severe toxicity mandated withdrawal or until the patient asked to be removed from the study. RESULTS The objective response rate for all patients was 34% (95% confidence interval [CI], 25% to 44%): 35% (95% CI, 23% to 48%) for first-line patients and 32% (95% CI, 20% to 47%) for second-line patients. Nine first-line and three second-line patients obtained a complete response (CR). The median duration of objective response was 34 weeks in both groups. The overall survival durations of first- and second-line patients were 67 weeks and 62 weeks, respectively. Granulocytopenia was the predominant dose-limiting toxicity. Two patients died on study as a result of granulocytopenic sepsis. CONCLUSION Single-agent vinorelbine is an effective and well-tolerated agent for first- and second-line therapy of ABC. The results of this study confirm the findings of similar international trials and suggest vinorelbine should be considered a valid treatment option for patients with ABC and a potential component in future combination regimens for this disease.

An economic analysis of axitinib and sorafenib for second-line treatment of cytokine-refractory patients with advanced renal cell carcinoma in the United States (US).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15601-e15601
Author(s):  
Ipek Özer-Stillman ◽  
Apoorva Ambavane ◽  
Paul Cislo
Keyword(s):  
Economic Analysis ◽  
The United States ◽  
Phase Iii ◽  
Administrative Claims ◽  
Line Treatment ◽  
Second Line ◽  
Cost Difference ◽  
Life Years ◽  
The Us ◽  
The Cost

e15601 Background: Cytokines are a first-line treatment option for a subset of advanced RCC patients in the US. After progression on cytokines, NCCN guidelines recommend targeted agents, such as axitinib and sorafenib. Subgroup analysis of post-cytokine patients in the phase III AXIS trial found that axitinib increased median progression free survival (PFS) compared with sorafenib (12.0 vs. 6.6 months, p<0.0001), while overall survival (OS) showed no difference (29.4 vs. 27.8 months, p=0.144). An economic analysis for this subgroup was conducted from a US healthcare payer perspective. Methods: A cohort partition model with monthly cycles was constructed to estimate direct medical costs and health outcomes, discounted at 3.0% per annum, over cohort lifetime. Patients were apportioned into 3 health states (progression-free, progressed and dead) based on OS and PFS Kaplan-Meier curves for the post-cytokine subgroup in the AXIS trial. Active treatment was applied until progression, followed by best supportive care (BSC) alone thereafter. The wholesale acquisition costs were based from RedBook. Adverse event (AE) management costs were obtained from published studies. AE rates and utility values were informed by the AXIS trial. Administrative claims data from MarketScan Database were analyzed to estimate costs for BSC and routine care of second-line advanced RCC patients. Results: The total per-patient lifetime costs were estimated to be $242,750 for axitinib and $168,880 for sorafenib and most of the cost difference (84%) was due to the higher total medication cost of axitinib. The cost difference was sensitive to dose intensity and length of treatment. The difference in quality-adjusted life-years (QALY) for axitinib versus sorafenib was minor (1.3 versus 1.2) and the incremental cost-effectiveness ratio (ICER) for axitinib compared with sorafenib was $683,209/QALY. Conclusions: For cytokine-refractory advanced RCC patients, axitinib resulted in an ICER > $650,000/QALY versus sorafenib due to high drug costs and lack of OS benefit, indicating that axitinib may not present good value for money as 2nd line treatment when compared to sorafenib in the US.

REVEL: A randomized, double-blind, phase III study of docetaxel (DOC) and ramucirumab (RAM; IMC-1121B) versus DOC and placebo (PL) in the second-line treatment of stage IV non-small cell lung cancer (NSCLC) following disease progression after one prior platinum-based therapy.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA8006-LBA8006 ◽  
Author(s):  
Maurice Perol ◽  
Tudor-Eliade Ciuleanu ◽  
Oscar Arrieta ◽  
Kumar Prabhash ◽  
Konstantinos N. Syrigos ◽  
...  
Keyword(s):  
Disease Progression ◽  
Primary Endpoint ◽  
Objective Response ◽  
Pulmonary Hemorrhage ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Double Blind

LBA8006^ Background: RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The REVEL study evaluated the efficacy and safety of RAM+DOC vs. PL+DOC (DOC) in patients (pts) with stage IV nonsquamous (NSQ) and squamous (SQ) NSCLC after platinum-based therapy. Methods: Pts with NSQ and SQ stage IV NSCLC were randomized 1:1 (stratified by sex, region, ECOG PS, and prior maintenance therapy) to receive DOC 75 mg/m2 in combination with either RAM 10 mg/kg or PL on day 1 of a 21-day cycle until disease progression, unacceptable toxicity, or death. The primary endpoint was overall survival (OS). Secondary efficacy endpoints included progression-free survival (PFS), and objective response rate (ORR). Results: Between Dec 2010 and Feb 2013, 1,253 pts (26.2% SQ) were randomized (RAM+DOC: 628; DOC: 625). Pt characteristics were balanced between arms. ORR was 22.9% for RAM+DOC and 13.6% for DOC (P<0.001). The hazard ratio (HR) for PFS was 0.762 (P<0.0001); median PFS was 4.5 months (m) for RAM+DOC vs. 3.0m for DOC. REVEL met its primary endpoint; the OS HR was 0.857 (95% CI 0.751, 0.98; P=0.0235); median OS was 10.5m for RAM+DOC vs. 9.1m for DOC. OS was longer for RAM+DOC in most pt subgroups, including SQ and NSQ histology. Grade ≥3 adverse events (AEs) occurring in >5% of pts on RAM+DOC were neutropenia (34.9% vs. 28.0%), febrile neutropenia (15.9% vs. 10.0%), fatigue (11.3% vs. 8.1%), leukopenia (8.5% vs. 7.6%), hypertension (5.4% vs. 1.9%), and pneumonia (5.1% vs. 5.8%). Grade 5 AEs were comparable between arms (5.4% vs. 5.8%), as was pulmonary hemorrhage (any grade; all pts: 2.1% vs. 1.6%; SQ pts: 3.8% vs. 2.4%). Conclusions: REVEL demonstrated a statistically significant improvement in ORR, PFS, and OS for RAM+DOC vs DOC in NSCLC pts with stage IV NSCLC as second-line treatment after platinum-based therapy. Benefits were similar in NSQ and SQ pts, and no unexpected AEs were identified. Clinical trial information: NCT01168973.

Duration of second-line T-DM1 therapy: Is it associated with duration of first-line anti-Her2 therapy in metastatic HER2 + breast cancer?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12512-e12512
Author(s):  
Daniela Katz ◽  
Ilan Feldhamer ◽  
Sari Greenberg-Dotan ◽  
Ariel Hammerman
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Her2 Overexpression ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Duration Of Treatment ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer ◽  
Line Standard

e12512 Background: Tumors with HER2 overexpression usually respond to HER2-targeted therapies. Since the CLEOPATRA and EMILIA trials, a taxane plus trastuzumab and pertuzumab (TTP) are the first-line standard for the management of HER2 + metastatic breast cancer (MBC) and trastuzumab emtansine (TDM-1) is the second-line standard. Intrinsic subtypes existing within HER2+ tumors may impact the degree of a patient’s response to anti HER2 therapy; however HER2 subtyping for predicting response is still experimental and not in routine clinical use. In this retrospective population-based study, we aimed to assess whether duration of treatment (DOT) of second-line TDM1 is associated with the DOT of first-line TTP, and might serve as a hint for a HER2 subtype. Methods: Clalit Health Services (CHS) manages health care of 52% of the Israeli population. We identified 113 HER2+ CHS MBC patients, treated with TTP as first-line treatment that initiated TDM1 as second-line, until Dec. 31, 2016. Patient's (pts) demography, HER2 and HR status were recorded. A Cox proportional hazard model, stratified by HR status, adjusted for age and prior adjuvant trastuzumab, was used to explore the association between second-line and first-line DOT in HR positive and negative pts. Results: Pts baseline characteristics and DOT in first- and second-line treatment are presented in the table. A statistically significant association between DOT of both treatment lines was found in HR positive pts with a trend also in HR negative pts. Conclusions: The observed association between first- and second-line DOT, unrelated to hormonal status, may result from a primary characteristic of the intrinsic tumor subtype, that impacts acquired resistance. Longer observations in larger patient cohorts are required to confirm this observation. [Table: see text]

Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer: ERIGE trial on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1095-1095
Author(s):  
Antonino Musolino ◽  
Rosa Porzio ◽  
Daniela Rubino ◽  
Antonio Frassoldati ◽  
Alessia Caldara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Objective Response ◽  
Locally Advanced ◽  
Combination Regimen ◽  
Line Treatment ◽  
Second Line ◽  
Tumor Cell Death ◽  
Study Population

1095 Background: There are no well-established chemotherapy regimens for metastatic triple negative breast cancer. The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, especially in tumors like triple negative breast cancers (TNBC) characterized by high cell proliferation, aggressive tumor behavior, and chemo-resistance. Methods: We performed an open-label, national multicenter phase 2 study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on day 1 and 8, q21 as either first- or second-line treatment of locally advanced or metastatic TNBC. The Simon's optimal two-stage design was used for estimating objective response rate (ORR) as study primary endpoint. A prospective, molecular correlative study was carried out on germinal DNA of study population to assess the role of germinal DNA polymorphisms and BRCA mutations in predicting efficacy and toxicity of the combination regimen. Results: From July 2013 to September 2016 , 83 (37 in the first stage, 46 in the second one) assessable patients were enrolled. Median age at baseline was 56 years. Sixty-six and 17 patients were in first or second-line treatment, respectively. All patients were previously treated with an anthracycline and/or a taxane. With regard to the first stage of study enrolment, patients received a median number of 6 cycles of treatment. The ORR (CR+PR) was 43.24% (90% CI 29.3-58.0) and the clinical benefit rate (CR+PR+SD) was 64.9% (90% CI: 50.1%-77.8%). The most common grade 3/4 AEs ( > 10% of patients) were neutropenia without febrile neutropenia and liver toxicity. Grade 1/2 AEs were fatigue, anemia, thrombocytopenia, diarrhea, alopecia, peripheral neuropathy, and oral mucositis. Conclusions: The combination of eribulin and gemcitabine shows promising activity and a moderate toxicity profile in metastatic TNBC. More mature toxicity and outcome data of the final study population and correlation with genome analysis will be presented at the meeting. Clinical trial information: 2012-003505-10.

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