Preliminary results of a multicenter phase II trial of vinflunine (with trastuzumab in HER2+ pts) as first-line treatment in metastatic breast cancer

1043 Background: Vinflunine (VFL) is a new and innovative microtubule inhibitor of the vinca alkaloid class that achieves high intracellular concentrations. By inhibition of tubulin polymerization, cell proliferation is arrested leading to apoptotic death. Demonstrating anti- angiogenic and vascular disrupting activities, VFL has demonstrated significant efficacy as 2nd line chemotherapy in MBC (M. Campone, BJC 2006). This trial was designed to evaluate the response rate and safety of VFL as 1st line therapy in MBC as well as its activity in combination with trastuzumab in HER2+ MBC pts. Methods: Eligibility: 0 prior regimens for MBC, > 6 mo from adjuvant therapy, RECIST measurable disease, ECOG PS 0–2, adequate organ function, < G2 neuropathy. Treatment: 320 mg/m2 IV over 20 minutes q3 weeks; 280 mg/m2 with trastuzumab 6 mg/kg q3 weeks in HER2+ pts. Response evaluations q9 weeks; treatment continued until progression or toxicity. A total of 96 pts will be enrolled, 48 pts per each of 2 cohorts, HER2- and HER2+. Results: 18 pts are enrolled, 13 pts evaluable for toxicity and 12 pts for response. 3 pts received VFL monotherapy and 10 pts were treated with VFL + trastuzumab. Median age: 59 years (43–78). ECOG PS 0: 9 pts, 1: 3 pts, 2: 1 pt. Prior adjuvant chemo: 7 pts (54%), with 5 prior anthracyclines and 6 prior taxanes. 2 pts received adjuvant hormonal therapy only. 4 pts presented with de novo stage IV HER2+ MBC. Metastatic disease sites: liver: 6 pts, lung: 7 pts, bone: 5 pts, lymph nodes: 6 pts. 46% had 3 or more sites of organ involvement. Median of 3 cycles (range:1 - 11) was delivered. 7 pts (58%, all HER2+) had a PR and 4 pts (33%) achieved SD. Only 1 pt progressed. Heme toxicity: G3/4 neutropenia: 2 pts (16%); no febrile neutropenia was noted. G3 non-heme toxicity consisted of N/V: 2 pts and myalgia, 2 pts. There were no G4 events. 4 pts were hospitalized (vomiting: 2, cerebro-vascular accident: 1, back pain: 1 pt). 92% of pts remain free of progression at 6 months. Median TTP has not been reached. Conclusions: Vinflunine is a promising new drug with a high level of activity as first line MBC therapy, especially in combination with trastuzumab. VFL is well tolerated in this patient population with a manageable toxicity profile. Accrual to this trial continues. [Table: see text]

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Cisplatin and etoposide as first-line chemotherapy for metastatic breast carcinoma: a prospective randomized trial of the Italian Oncology Group for Clinical Research.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.4.664 ◽

1991 ◽

Vol 9 (4) ◽

pp. 664-669 ◽

Cited By ~ 46

Author(s):

G Cocconi ◽

G Bisagni ◽

M Bacchi ◽

C Boni ◽

R Bartolucci ◽

...

Keyword(s):

Randomized Study ◽

Metastatic Breast ◽

Hematologic Toxicity ◽

First Line ◽

Metastatic Breast Carcinoma ◽

Level Of Activity ◽

Duration Of Response ◽

Gastrointestinal Side Effects ◽

High Level ◽

Line Chemotherapy

In this prospective randomized study, first-line treatment with the combination of cisplatin (P) and etoposide (E) was compared with the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in 140 patients. Complete remissions were obtained in 11% of 65 assessable patients on CMF and in 12% of 65 assessable patients on PE. Complete plus partial remission rates were 48% on CMF and 63% on PE (P = .08). Time to progression (median, 32 v 31 weeks), duration of response (48 v 39 weeks), and survival (75 v 76 weeks) were not different. Hematologic toxicity was significantly higher with PE, and gastrointestinal side effects were frequent with this treatment. This study demonstrated that the PE combination is effective as front-line chemotherapy. As far as response rate is concerned, a trend of superiority over CMF was observed, which was of borderline significance. Due to the lack of survival advantage and to toxicity, this combination is not recommended for routine clinical use. However, its high level of activity should be taken into account for further research.

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Pan-cancer evaluation of homologous repair deficiency somatic mutations and response to first-line anti-neoplastic therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.10535 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 10535-10535

Author(s):

Jessica A Lavery ◽

Samantha Brown ◽

Gregory J. Riely ◽

Philippe L. Bedard ◽

Ben Ho Park ◽

...

Keyword(s):

Somatic Mutations ◽

De Novo ◽

Stage Iv ◽

Progression Free Survival ◽

First Line ◽

Major Mechanism ◽

First Line Therapy ◽

Oncogenic Mutation ◽

Line Therapy ◽

Response To Chemotherapy

10535 Background: Homologous recombination is a major mechanism of defective DNA repair, but it remains uncertain whether homologous repair deficient (HRD) tumors have favorable prognosis or are more/less likely to respond to treatment than tumors lacking such mutations. Objective: To determine whether lung (NSCLC) and colorectal (CRC) HRD+ tumors have better survival or response to chemotherapy than HRD- tumors. Methods: Patients with de novo stage IV NSCLC or CRC who had next generation sequencing (NGS) between 2015-2018 from one of four cancer centers were identified. Records were curated using the PRISSMM framework to ascertain treatment, overall survival (OS) and progression free survival based on imaging (PFS-I) and oncologists’ notes (PFS-M). Each NSCLC or CRC tumor was categorized as HRD+ if NGS revealed an oncogenic/likely oncogenic mutation in: ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, PALB2, RAD50, RAD51, RAD51C, RTEL1, or MRE11A based on the OncoKB database. The tumor was categorized as HRD- if no oncogenic mutation in any of these genes was evident and HRD indeterminate (HRD?) if no mutation was identified but the panel did not include all genes. OS, PFS-I and PFS-M from start of first line therapy were reported by HRD status. The percentage with a good response to first line therapy (≥2x the median) and exceptional response (≥3x the median) was estimated for each endpoint. Results: For NSCLC 4% were HRD+, 59% HRD- and 37% HRD?. For CRC there were 5% HRD+, 60% HRD- and 35% HRD?. There were no significant differences for any survival endpoint between patients who were HRD+ vs HRD- in univariable analyses. The proportion of good and exceptional responders to first line systemic chemotherapy also did not vary by HRD status, though patients with HRD+ CRC were potentially more likely to be exceptional responders. Similarly, no differences between HRD+ and HRD- tumors were apparent for the subgroup receiving platinum containing therapy. Conclusions: NSCLC and CRC patients with somatic mutations in HRD oncogenic genes did not differ from patients lacking such a mutation with respect to OS or PFS. CRC patients with HRD+ tumors may be more likely to be exceptional responders, but sample sizes are limited. By May, the analysis will include breast and pancreatic cancer cases.[Table: see text]

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Randomized open label phase II study of pegilated liposomal doxorubicine (PLD) four or six-week scheduled in metastatic breast cancer (MBC) patients (p)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10751 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10751-10751 ◽

Cited By ~ 1

Author(s):

M. Ruiz ◽

J. L. Bayo ◽

J. A. Moreno Nogueira ◽

J. Dorta ◽

A. M. Casas ◽

...

Keyword(s):

Median Time ◽

Ductal Carcinoma ◽

Metastatic Breast ◽

Stage Iv ◽

Dose Intensity ◽

Primary Objective ◽

Comparable Efficacy ◽

Toxicity Profile ◽

Open Label ◽

Ecog Ps

10751 Background: PLD has the advantage of delivering the active anthracycline directly to the tumour site, provide comparable efficacy to conventional doxorubicin with a more favourable toxicity profile and significantly less cardiotoxicity. The most frequent dosing schedule is 50 mg/m2 every 4 weeks. Recent studies have shown that PLD 60 mg/m2 every 6 weeks is an active and well tolerated treatment, and could be more convenient for the p. The primary objective was to evaluate response rate in six- and four-week schedule (arms A and B). Secondary objective was toxicity profile. Methods: P histologically confirmed of MBC, age 18–75 years old, ECOG PS ≤ 2, at least one measurable lesion and adequate bone marrow, renal, hepatic and cardiac function, were eligible. Prior chemotherapy with anthracyclines for MBC or adjuvant anthracycline-based regimen in the previous 12 months was not allowed. P were randomly assigned to receive PLD 60 mg/m2 i.v. in 1 hour every 6 weeks (arm A) or PLD 50 mg/m2 i.v. in 1 hour every 4 weeks (arm B). Results: Ten p have been included in the interim analysis over 11 enrolled, with median age of 50 years, ECOG PS 0–1 70% and stage IV 50%. Median time from diagnosis of metastatic disease was 9.2 months. Histology: 80% of p had ductal carcinoma, 10% lobular and 10% undifferentiated. Main tumour locations were lung (60%), liver (60%) and bone (40%). Two p had positive hormonal receptor status in arm A and 4 in arm B. Previous treatment included chemotherapy (80%), hormonotherapy (80%) and radiotherapy (40%). Up to date, a total of 15/17 cycles (median 3/3, range 1–6/1–5) were administered. Absolute dose intensity was 2.2 mg/day in arm A and 3.0 mg/day in arm B. Two p were not evaluated and over 8 evaluable p for efficacy (4 A and 4 B), 2 achieved partial response in arm A and 1 in arm B. Median time to progression was 168 days in arm A and 104 in arm B. The only grade III/IV toxicity was mucositis and stomatitis in 4 p. The most common grade I/II toxicities were palmar-plantar erythrodysesthesia (5p), anorexia (4p) and alopecia (4p). Conclusions: PLD at 50 mg/m2 every 4 weeks and 60 mg/m2 every 6 weeks are effective and well tolerated regimens in MBC p. The most relevant adverse events were mucositis and palmar-plantar erythrodysesthesia. No significant financial relationships to disclose.

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Docetaxel (T) followed by capecitabine (X) as first-line chemotherapy in patients (pts) with metastatic breast cancer (MBC): Preliminary findings from a phase II study

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10692 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10692-10692

Author(s):

J. L. Bayo ◽

M. Lomas ◽

J. Salvador ◽

M. Ruiz ◽

A. Moreno

Keyword(s):

Phase Ii ◽

Phase Ii Study ◽

Metastatic Breast ◽

Dose Intensity ◽

First Line ◽

Recent Trial ◽

Highly Active ◽

Grade 3 ◽

Metastatic Sites ◽

Ecog Ps

10692 Background: X and T are highly active single agents in MBC. The XT combination leads to superior overall survival (OS), time to progression (TTP) and response rate (RR) vs. T alone in anthracycline-pretreated MBC [O’Shaughnessy et al. J Clin Oncol 2002]. The aim of this trial was to evaluate the efficacy and safety of sequentially administered T then X as first-line treatment in MBC. Methods: Pts ≥ 18 years with previously untreated, HER2neu-negative MBC, ECOG PS ≤ 2, were included in this prospective, multicenter, non-randomized, phase II study. Pts received 3 cycles of T (100mg/m2 d1) followed by 3 cycles of X (1250mg/m2 bid d1–14), every 3 weeks. Results: To date, 38 pts are evaluable for safety and 33 pts for efficacy. Baseline characteristics: median age 54.4 years (range 33–76); PS ≥ 1 50%; 36 (95%) pts had previous (neo)adjuvant anthracyclines, 8 (21%) concomitant with paclitaxel. The most frequent metastatic sites were: bone 47%, nodes 39% and liver 36%. 69% of pts had ≥ 2 metastatic sites. To date, 38 pts have received 3 cycles of T and 33 have also received 3 cycles of X. A total of 195 cycles have been administered: T 108 cycles (median 3, range 1–3); X 87 cycles (median 3, range 1–3). Dose reductions and interruptions for T vs. X were 32 vs. 21% and 21 vs. 21%, respectively. Median relative dose intensity: T 0.97 (range 0.62–1.00), X 0.93 (range 0.26–1.00). T grade 3/4 toxicities (37 evaluable pts): asthenia 19%, mucositis 16%, nausea 13%, febrile neutropenia 11%, rash 5%, diarrhea 5%, infection 3%. X grade 3/4 toxicities (33 evaluable pts): hand-foot syndrome 9%, diarrhea 9%, vomiting 9%, asthenia 6%, nausea 3%, anorexia 3%. In the 33 pts evaluable for efficacy, the RR was 61%, including 4 CRs and 16 PRs. At a median follow-up of 6.1 months, median TTP has not yet been reached. Conclusions: These preliminary results show that the sequential regimen of T followed by X is feasible, effective and well tolerated in first-line MBC, although giving X before T should also be investigated. Findings from a recent trial of XT vs. T followed by X [Beslija et al. ECCO 2005] suggest that XT should be standard in fit poor-prognosis pts with aggressive disease. No significant financial relationships to disclose.

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Randomized phase II study of biweekly gemcitabine (gem)-paclitaxel (pac), gem-carboplatin (carb) and gem-cisplatin (cis) as first-line treatments in metastatic breast cancer (MBC) after anthracycline failure

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1099 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1099-1099 ◽

Cited By ~ 2

Author(s):

B. Xu ◽

Z. Jiang ◽

S. Kim ◽

S. Yu ◽

J. Feng ◽

...

Keyword(s):

Performance Status ◽

Metastatic Breast ◽

Stage Iv ◽

Ecog Performance Status ◽

Eligibility Criteria ◽

Dominant Type ◽

Tumor Involvement ◽

Number Of Cycles ◽

Ecog Ps ◽

Tumor Types

1099 Background: Biweekly gem-pac and gem-cis regimens have shown promising activity and safety in different tumor types. In MBC biweekly gem-pac is active and well tolerated. The aim of this multi-country study is to evaluate the efficacy and safety of gem in combination with pac, carb or cis on a biweekly schedule in patients (pts) with MBC. Methods: Major eligibility criteria included: tissue diagnosis of stage IV breast carcinoma; prior anthracycline therapy; ECOG performance status (PS) of 0 or 1; and written informed consent. Pts were randomized to receive gem 2500 mg/m2 in combination with pac 150 mg/m2 (Arm A), carb AUC 2.5 (Arm B) or cis 50 mg/m2 (Arm C) on day 1 of 2-week cycles. The primary endpoint was response rate, with safety a secondary endpoint. Results: This interim analysis was planned to occur when patient enrollment had reached 50% (75/150 pts), at which point there were 26 pts in Arm A, 25 in Arm B and 24 in Arm C, with 12 pts still on treatment. The baseline characteristics were similar in the three arms, including mean age (Arm A 50.2 yr, Arm B 46.1, Arm C 47.3); ECOG PS (PS 0: 50.0%, 64.0%, 54.2%); mean number of sites of tumor involvement (2.9, 2.6, 2.7); dominant type of metastasis (visceral: 73.1%, 80.0%, 79.2%); and disease-free interval (<24 mo: 53.8%, 60.0%, 41.7%). The mean number of cycles was 6.4, 6.0 and 5.8. There was a partial response in 5/26 efficacy qualified pts (19.2%), 5/25 pts (20.0%) and 2/23 pts (8.7%) in Arms A, B and C, respectively, stable disease in 10 pts (38.5%), 9 pts (36.0%) and 9 pts (39.1%), and progressive disease in 5 pts (19.2%), 6 pts (24.0%) and 6 pts (26.1%). There were no treatment-related deaths. Conclusions: The three regimens appear to show activity and have manageable toxicity when given on a biweekly schedule. [Table: see text] No significant financial relationships to disclose.

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First-line cisplatin (P) with docetaxel (TXT) or vinorelbine (VNR) in patients with advanced non-small cell lung cancer: A randomized phase II trial of the Gruppo Oncologico Italia Meridionale

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e19042 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e19042-e19042

Author(s):

V. Gebbia ◽

D. Galetta ◽

V. Lorusso ◽

M. Caruso ◽

F. Riccardi ◽

...

Keyword(s):

Advanced Nsclc ◽

Response Rate ◽

Phase Ii Trial ◽

Stage Iv ◽

Hematological Toxicity ◽

First Line ◽

Primary Endpoints ◽

Randomized Phase Ii ◽

P 75 ◽

Ecog Ps

e19042 Background: P-based doublets are considered standard therapy for advanced NSCLC. The GOIM consider P/VNR as a reference treatment. P/TXT doublet has been reported to be active but it's not well known its real impact on QoL in comparison to P/VNR. Methods: Pts received either 6 courses of P/TXT or P/VNR with QoL and safety being the primary endpoints. Secondary endpoint included response rate, TTP, OS, and tolerability. Patients with stage IV/IIIB, age ≤70, and ECOG PS 0–1, were eligible. Sample size was calculated according to Fleming's single-stage procedure. QoL was analysed using the EORTC questionnaire, responses and toxicity according to the RECIST and NCI-CTC criteria. Pts were randomized to: TXT 75 mg/m2 over 60 min followed by P 75 mg/m2 on d1 every 21 d, or VNR 30 mg/m2 on d 1,8 and P 80 mg/m2 on d1 every 21 d. Results: From 12/06 to 3/08 86 pts were enrolled: P/TXT 42pts, M/F 32/10, IIIB/IV 8/34, squamous/not-squamous:13/29, median age 61 (r 41–70); P/VNR 44 pts, M/F 35/9, IIIB/IV 10/33, squamous/not-squamous 14/30, median age 62 (r 44/70). No statistically significant differences were observed in QoL among the two arms. Detailed analysis of side-effects showed no difference among the two regimens with the exception of G3–4 neutropenia and leukopenia with were slightly higher in the P/VNR arm (p=0.02 and p=0.0005 respectively). The use of G- CSF/darbopoietin was more frequent in pts treated with P/VNR than in the P/TXT arm (p=0019). Conclusions: Final data show an equivalence among the two arms regarding QoL and activity but with a slightly more hematological toxicity in the P/VNR arm. Both regimens are to be considered as standards in the treated of advanced NSCLC. [Table: see text]

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Retrospective analysis of ribociclib and letrozole as first-line therapy in patients with hormone receptor (HR) positive metastatic breast cancer (MBC) within a managed access program (MAP) in Turkey.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13055 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13055-e13055

Author(s):

Gul Basaran ◽

Umut Demirci ◽

Fatih Yildiz ◽

Irfan Cicin ◽

Burak Yasin Aktas ◽

...

Keyword(s):

Ovarian Function ◽

De Novo ◽

Metastatic Breast ◽

Retrospective Chart Review ◽

Qtc Interval ◽

First Line ◽

Ovarian Function Suppression ◽

First Line Therapy ◽

Line Therapy ◽

Her 2

e13055 Background: The combination of ribociclib with ET significantly increased progression free survival (PFS) and OS compared with ET in first line treatment of HR positive HER2 negative MBC. We aimed to evaluate the efficacy and safety of ribociclib and letrozole within Turkish MAP in order to present clinical outcome with the real-world use of ribociclib, outside of clinical trial setting. Methods: Turkish MAP enabled access to ribociclib in combination with letrozole as first-line therapy for MBC patients with HR positive and Her-2 negative tumors. Adequate bone marrow reserve, a normal QTc interval, normal renal and liver functions were required for eligibility. Patients received 600 mg ribociclib once daily for 3 wks followed by 1wk off. A retrospective chart review of patient demographics, clinical and treatment characteristics have been performed. Results: Between July and November 2017, 178 patients were included from 47 institutions in Turkey. We report the results of first 101 patients analyzed. The median age was 53 years (33–81 years) and median follow up was 16 months. Forty-six patients had de novo disease, 78% patients were postmenopausal, 22% had ovarian function suppression. Thirty-six % patients had adjuvant chemotherapy, 49% received adjuvant ET. Forty % had visceral disease. Thirty patients had grade 3 neutropenia, 3 patients had febrile neutropenia, 5 patients have grade 2-3 elevation of liver function tests. There was no QT prolongation. Dose reduction to 400 mg was required for 16 patients. Four patients discontinued ribociclib due to toxicity, 22 patients due to progression, one patient refused treatment. Twelve patients had complete remission as their best response. Median PFS was 24.12 months (95%CI 22.2-26.2). None of the clinical and pathologic factors were significantly associated with prolonged PFS. Conclusions: The efficacy and toxicity of first-line ribociclib and letrozole within Turkish MAP is similar to the results from randomized clinical studies for patients with HR positive, Her-2 negative MBC.

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Readiness of health care systems to generate RWE: Frequency of radiographic imaging of metastatic disease during first-line systemic therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.29_suppl.268 ◽

2020 ◽

Vol 38 (29_suppl) ◽

pp. 268-268

Author(s):

Brandon Chan ◽

David Cameron ◽

Aria Shokoohi ◽

Dean Regier ◽

Howard John Lim ◽

...

Keyword(s):

Lung Cancer ◽

Health Care ◽

Clinical Practice ◽

Metastatic Disease ◽

Real World ◽

Systemic Therapy ◽

De Novo ◽

Metastatic Breast ◽

Ct Imaging ◽

First Line

268 Background: Regulatory and Health Technology Assessment (HTA) agencies are increasingly using real world data (RWD) to support real world evidence (RWE), but the readiness of healthcare systems to reliably generate RWE is unknown. As a quality assurance measure we examined the preparedness of a single payer system to provide RWE by evaluating the frequency of CT imaging during standard first line metastatic systemic treatment of breast, colorectal (CRC) and lung cancer. Methods: A 1-year cohort of de novo metastatic breast, CRC, lung cancer patients treated with first line systemic therapy (excluding hormone therapy) referred to BC Cancer in 2016 was retrospectively reviewed. Duration of first line treatment was calculated from first to last dose of therapy. Baseline CT included imaging within 8 weeks prior to and 3 weeks after treatment initiation (first cycle). Last CT included imaging up to 8 weeks after the last dose of therapy. Results: A cohort of 675 patients was identified from the BC Cancer Registry. The distribution of de novo metastatic disease at diagnosis was lung (n = 379), CRC (n = 214) followed by breast cancer (n = 82). Conclusions: In our publicly funded health care system, baseline CT scans within 4 weeks prior to treatment ranged from 57-72%. The median CT imaging interval during first line metastatic treatment was ranged from 7.9-11.3 weeks. RWD from routine clinical practice differs significantly from clinical trials, the gold standard for regulatory and HTA assessments. Population-based data may contribute to RWE with caution due to limitations imposed by clinical practice. [Table: see text]

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Interim safety results of eribulin (E) combined with ramucirumab (RAM) in patients (pts) with advanced metastatic breast cancer (MBC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.27_suppl.110 ◽

2012 ◽

Vol 30 (27_suppl) ◽

pp. 110-110 ◽

Cited By ~ 1

Author(s):

Denise Aysel Yardley ◽

Cynthia R. C. Osborne ◽

Paul D. Richards ◽

Brooke R. Daniel ◽

Michael A. Danso ◽

...

Keyword(s):

Breast Cancer ◽

Vascular Function ◽

Antiangiogenic Therapy ◽

Tumor Hypoxia ◽

Metastatic Breast ◽

Dose Intensity ◽

Sensory Neuropathy ◽

Microtubule Inhibitor ◽

Prior Chemotherapy ◽

Ecog Ps

110 Background: VEGF-mediated angiogenesis contributes to breast cancer (BC) pathogenesis. RAM (IMC-1121B), a fully human IgG1 monoclonal antibody (MAb), targets VEGFR-2, blocking the interaction of VEGF ligands and VEGFR‑2. DC101 (murine anti-VEGFR-2 MAb) impairs vascular function and increases tumor hypoxia in xenograft BC models and inhibits tumor growth in cytotoxic-resistant models. E is a novel non-taxane microtubule inhibitor indicated in MBC pts who have received ≥2 prior chemotherapy regimens, including an anthracycline and a taxane. It is hypothesized that addition of RAM to E as 3rd-5th line therapy in MBC will result in an improvement of median PFS in this ongoing, multicenter, US study. A planned safety analysis of an initial cohort is reported. Methods: Pts with locally recurrent or MBC (HER2+ or HER2-) and 2-4 prior chemotherapy regimens are randomized 1:1 to receive RAM+E or E (E 1.4 mg/m2 Days 1, 8; RAM 10 mg/kg Day 1; q21 days). Pts are stratified by TNBC and prior antiangiogenic therapy status and must have ECOG PS 0-1 and normal LVEF. Planned accrual: 134 pts. Results: Evaluable pts (n=13, 8 RAM+E) received ≥1 dose of RAM+E or E and completed 2 cycles of therapy (or discontinued prior to completing the initial 2 cycles). Median age is 55 yrs. Assessment of adverse events (all cause) revealed nausea, fatigue, headache, and neutropenia were more frequent for RAM+E; anemia was more frequent for E. G1 sensory neuropathy was reported for 1 pt in each arm. One RAM+E pt experienced G3 febrile neutropenia and odynophagia, recovered within a week, and subsequently received reduced dosage (E = 1.1 mg/m2; RAM = 8 mg/kg). No deaths are reported. The safety assessment committee recommended to continue the trial unmodified. Conclusions: Based on preliminary data, the combination of RAM+E demonstrates an acceptable toxicity profile. Accrual continues, with planned updated safety and dose intensity data to be presented at the meeting. [Table: see text]

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