bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase II study of weekly versus every-3-week ixabepilone plus bevacizumab (ixa/bev) versus paclitaxel plus bev (pac/bev) as first-line therapy for metastatic breast cancer (MBC)
Authors: Rugo H. S. , Campone M. , Amadori D. , Wardley A. , Villa E. , Conte P. F. , Mudenda B. , McHenry B. , Pivot X. 
Published: August 2020

1029 Background: Pac/bev is superior to pac alone as first-line therapy for MBC. Ixa/bev has greater preclinical activity than pac/bev in human tumor models. The primary objective of this trial was to evaluate objective response rates (ORR) of ixa/bev given weekly or every 3 weeks relative to pac/bev as 1st line therapy for women with advanced breast cancer. Methods: Women with measurable disease and no prior chemotherapy for advanced breast cancer (locally advanced or MBC) were randomized in a 3:3:2 ratio to Arm A (ixa 16 mg/m2 IV on days 1, 8 & 15 q28 days/ bev 10 mg/kg IV q 2 wks), Arm B (ixa 40 mg/m2 IV q3 wks / bev 15 mg/kg IV q 3 wks) or Arm C (pac 90 mg/m2 IV, schedule/bev as in Arm A). Treatment was continued until disease progression or unacceptable toxicity. Results: Key efficacy and safety results from a pre-planned analysis of all randomized subjects after at least 24 weeks of follow-up are presented. Baseline characteristics were balanced between arms except for liver metastasis. Conclusions: The combination of ixa/bev weekly or q 3 wks demonstrated encouraging clinical activity and safety comparable to 1st line pac/bev in E2100. Final PFS will be provided when data is mature. These results support ongoing clinical trials of ixa given weekly or q 3wk in 1st line MBC, and in combination with bev. [Table: see text] [Table: see text]
Tolerability and efficacy of first-line bevacizumab (B) plus chemotherapy (CT) in elderly patients with advanced breast cancer (aBC): Subpopulation analysis of the MO19391 study
Authors: Biganzoli L. , Cortes-Funes H. , Thomssen C. , Pritchard K. I. , Pierga J. , Kupp A. , Borstnar S. , Smith I. 
Published: August 2020

1032 Background: Limited data exist on the efficacy and safety of biological agents in elderly patients with aBC. This is essentially due to the lack of studies specifically targeting the older population and to strict inclusion criteria in clinical trials. B significantly improved the efficacy of 1st-line taxane therapy in two large, randomized phase III trials, E2100 and AVADO. Methods: In study MO19391, 1st-line B 10mg/kg q2w or 15mg/kg q3w + CT (primarily but not exclusively taxane monotherapy) was investigated in a broader, large aBC patient population, with the aim of understanding safety and efficacy in patients seen in routine clinical practice, including elderly patients. Results: A total of 2,027 patients were enrolled. Median age was 54 years (range 21–93); 359 patients (17.7%) were aged ≥65 years and 169 (8.3%) were ≥70 years. Baseline characteristics and safety and efficacy results according to age are shown below (Table). Conclusions: Treatment with B is feasible in elderly patients. Hypertension was the only grade 3 B-related side effect reported more frequently in the older than in the younger cohort. Efficacy was similar in the two subgroups. These results suggest that the combination of B with 1st-line CT shows a similar therapeutic index regardless of age. Data on compliance according to the different CT regimens, the impact of comorbidities on safety, and analyses in the subgroup of patients ≥70 years will be presented. [Table: see text] [Table: see text]
Long-term treatment with intravenous bisphosphonates in metastatic breast cancer (MBC)
Authors: Onishi T. , Singh V. , Rosenzweig M. , Sereika S. , Brufsky A. M. 
Published: August 2020

1035 Background: Intravenous bisphosphonates (IV BPs) are safe and effective in reducing skeletal related events in MBC. The effects of IV BPs after 24 months of therapy are unknown. The incidence of osteonecrosis of the jaw (ONJ) and renal insufficiency (RI) among women with MBC receiving >= 24 months of IV BPs is also poorly defined. We studied the long term effect of IV BPs in a cohort of women with MBC. Methods: We maintain an ongoing prospective database of >600 women with MBC diagnosed and treated at our institution from January 1999. A long-term cohort (LTC) of 159 women with metastatic breast cancer to bone treated for >= 24 months with pamidronate (n = 9), zoledronic acid (n = 110), or both (n = 40) was identified. A control cohort (CC) of 62 women with MBC to bone treated with IV BPs for 12–23 months was also identified. RI was defined as an increase in serum creatinine (scr) of > 0.5 mg/dl or an absolute level of scr >1.5mg/dl; ONJ was diagnosed by dental consultation. Results: Median follow-up of the LTC was 39 months (range 24–99) months. Median overall survival in this cohort was 43 months (range 24–114). The vast majority of women in the LTC (140/159, 88.1%) continued to receive IV BPs at standard dose every 3–4 weeks. The incidence of ONJ in the LTC was 6/159 (3.8%), after a mean 42.2 treatment cycles, with a median time to ONJ of 44 months. Three of six patients with ONJ (50%) underwent surgical resection, and 3/6 (50%) were managed conservatively, and 3/6 (50%) resumed IV BPs after a mean 12 month hold. The incidence of RI (all pts had baseline scr < 1.4 mg/dl) in the LTC was 19/159 (11.9%), occurring after a mean 43.4 treatment cycles, with a median time to RI of 43 months. Eleven of 19 patients (57.9%) recovered to baseline scr and 7/19 (36.7%) patients showed partial recovery. Seventeen of 19 patients (89.4%) were able to resume therapy after temporary discontinuation, decreasing the dose, or increasing the interval of the IV BP. Incidence of ONJ in the CC was 1/62 (1.6%) and RI in the CC was 6/62 (9.7%). Conclusions: Long term (>=24 month) IV BP use in MBC is well tolerated and safe, with relatively low incidence of ONJ and RI. Most patients were able to resume IV BP therapy after a therapy hold without further complication. No significant financial relationships to disclose.
Risk and cost of anthracycline-induced cardiotoxicity among breast cancer patients in the United States
Authors: Choi J. C. , Chang J. D. , Seal B. , Tangirala M. , Mullins C. D. 
Published: August 2020

1037 Background: Onset of anthracycline-induced cardiotoxicity is well documented. However, information regarding the time of onset varies depending on literature. The purpose of this study was to compare the risk of cardiotoxicity among three cohort groups: anthracycline-containing-chemotherapy (ACC), no-anthracycline-containing-chemotherapy (NACC), and no-chemotherapy (control) groups. Methods: A retrospective cohort study was designed using commercial managed care claims database. Adult subjects (≥18) diagnosed with breast cancer, between January 1, 2002 to December 31, 2005, (index-period) were followed for 24 months. Subjects with a previous cardiotoxic events (CE), breast cancer diagnosis, or anthracycline-use 12-months prior to index date were excluded. Index date was the first chemotherapy claim date for ACC and NACC and non-chemotherapy medication claim date for controls. Cohorts were matched by index date and year of birth. CE was defined based on ICD-9-CM and Healthcare Common Procedure Coding System codes. Risk of CE was evaluated using a logistic model with and without adjusting for confounders. Results: 21,106 subjects were classified as ACC (n = 3,428), NACC (n = 7,125), and controls (n = 10,553). NACC cohort was significantly (p < 0.01) older (mean age: 62 years ±12.5) compared to ACC (53±9.7) or control cohorts (59±12.5). ACC cohort had a higher (p < 0.01) average degree of comorbidity, (1.8±0.8) compared to NACC (1.6±0.9) or control (1.3±0.8) as measured by Charlson comorbidity-index. Higher rates of CE were found within the ACC group compared to NACC and controls as early as month 3 post index-date and remained consistent over 24 months. At month 12 post index-date, 14% (n = 485) of ACC and 5% (n = 381) of NACC had CE compared to 3% (n = 310) of controls. After adjusting for all baseline differences, the odds ratio of CE compared to controls was 3.98 (95% CI: 3.27–4.85), and 1.31 (95% CI: 1.11–1.54) for ACC and NACC cohorts, respectively. The total mean costs were $59,287, $20,528, and $11,600, among ACC, NACC, and control cohorts respectively. Conclusions: Compared to NACC and controls, ACC cohorts had significantly higher risk of cardiotoxic events and seen as early as month 3 post treatment initiation. [Table: see text]
Lapatinib plus letrozole compared with letrozole alone as first-line therapy in hormone receptor positive HER2+ metastatic breast cancer (MBC): A quality-of-life (QOL) analysis
Authors: Sherif B. N. , Sherrill B. , Amonkar M. , Wu Y. , Maltzman J. , O'Rourke L. , Johnston S. 
Published: August 2020

1039 Background: A phase III randomized double-blind multicenter trial compared lapatinib plus letrozole (L+Let) with letrozole plus placebo (Let), as first-line therapy for hormone receptor positive (HR+) MBC. Median PFS, the primary endpoint of the study, in patients who were HER2+ was significantly prolonged for L+Let compared with Let (8.2 vs 3 months, Hazard Ratio (95% CI)=0.71(0.53,0.96), p=0.019). This analysis focuses on the impact of treatments on QOL in the HER2+ subgroup. Methods: QOL outcomes included the Functional Assessment of Cancer Therapy-Breast (FACT-B) total, FACT-general (FACT-G), and trial outcome index (TOI) scores assessed at screening, every 12 weeks and at withdrawal. Higher scores indicate better QOL. Changes from baseline were analyzed using analysis of covariance. In a responder analysis, patients achieving minimally important differences in QOL scores (QOL responders) were compared with Fisher's exact test. Results: Among 1,286 patients, 219 were identified as HER2+ (L+Let n=111; Let n=108). Baseline QOL scores were comparable in the two arms. In this population, mean changes in subscale and total QOL scores were generally stable over time in both treatment arms for patients who stayed on study. For example, on the FACT-B, the average change from baseline in both groups was positive at all scheduled visits through Week 48 and the maximum difference between arms was 2.6 points (CI: -5.8, 11). There were no significant differences between the two treatment arms in percentage of QOL responders (Table). Conclusions: The addition of lapatinib to letrozole significantly increases PFS while maintaining QOL when compared with letrozole alone thus confirming the clinical benefit of the combination therapy in the HR+, HER2+ MBC patient population. This combination provides an effective option in this patient population by maintaining QOL and delaying the need for chemotherapy and its accompanying side effects. [Table: see text] [Table: see text]
Correlations of estrogen receptor (ER) related genomic transcription and ER gene expression with increasing AJCC stage of ER-positive breast cancer
Authors: Andreopoulou E. , Hatzis C. , Booser D. , Valero V. , Wallace M. J. , Sotiriou C. , Hortobagyi G. , Pusztai L. , Symmans W. 
Published: August 2020

1044 Background: Advanced stages of ER-positive breast cancer may have decreased tumor dependence on estrogen, possibly due to biological selection and/or progression. The sensitivity to endocrine therapy (SET) index measures transcriptional activity of the ER genomic pathway (165 ER-related genes). We investigated whether expression of genes for receptors ER (ESR1), progesterone receptor (PGR), or HER-2 (ERBB2), the SET index, or a housekeeper gene (GAPDH) vary by stage of ER-positive breast cancer. Methods: We evaluated gene expression profiles (Affymetrix U133 microarrays, Affymetrix, Santa Clara, CA) from 956 patients’ clinical samples of ER-positive breast cancer, including 290 new samples profiled at MDACC and 666 samples from published datasets. Microarray data were uniformly normalized, log-transformed, and expression levels for single genes and the SET index were compared to pathologic AJCC stage (315 patients were stage I, 362 stage IIA, 151 stage IIB, 29 stage III, 27 stage IV at initial presentation, and 72 stage IV previously treated and/or at relapse) using a median ordered regression analysis (p < 0.05 was significant). Results: SET index significantly decreased with advancing pathologic stage (p < 0.001), and PGR expression levels showed a similar, but lesser, effect (p = 0.014). However, expression levels of ESR1 and ERBB2 did not vary by stage. Overall, GAPDH gene expression increased with stage (p < 0.001), but that effect was only observed in stages III and IV. Expression of these genes was not significantly different between stage IV disease at initial presentation or at relapse. Conclusions: Expression levels of ESR1 and ERBB2 receptor genes did not vary, but ER-related genomic transcription (SET index and, to a lesser extent, PGR) declined significantly with increasing pathologic stage. This suggests that ER-positive breast cancer tends to have less transcriptional dependence on estrogen with increasing pathologic stage. The observed increase in expression of GAPDH in stages III and IV might reflect higher metabolic activity in advanced ER-positive breast cancer and deserves further study. [Table: see text]
HER-2-PET imaging with 89Zr-trastuzumab in metastatic breast cancer patients
Authors: Oude Munnink T. , Dijkers E. , Lub-de Hooge M. , Kosterink J. , Brouwers A. , de Jong J. , van Dongen G. , de Vries E. 
Published: August 2020

1045 Background: Non-invasive diagnostic tools can optimize and evaluate HER2 directed therapy in HER2 positive breast cancer patients. HER2 imaging with 111In-trastuzumab SPECT showed promising results (Perik et al, J Clin Oncol. 2006). To further optimize HER2 imaging, we developed 89Zr-trastuzumab for high resolution, quantitative and sensitive PET imaging. A feasibility study was performed to determine optimal conditions (tracer dose and scans) for visualization HER2 positive lesions. Methods: Trastuzumab was labeled with 89Zr according to Verel et al. (J Nucl Med. 2003). HER-2 positive metastatic breast cancer patients received 37 MBq 89Zr-trastuzumab at 3 protein doses of trastuzumab: 1) 10 mg, or 2) 50 mg trastuzumab, or 3) 10 mg trastuzumab when on trastuzumab treatment. Patients underwent 2 or 3 PET-scans during 1–7 days post tracer injection. Images were analyzed visually and the relative tissue or tumor uptake was calculated as the ratio tissue/tumor to whole body uptake. Results: Fourteen patients were included. Optimal time point to assess 89Zr-trastuzumab tumor uptake was 4–5 days post injection. The tracer dose of 10 mg was sufficient for patients on trastuzumab treatment, while best imaging results in trastuzumab naive patients were obtained with the 50 mg dose as 10 mg resulted in rapid tracer clearance. In trastuzumab naive patients, 89Zr-trastuzumab clearance was not only dose-dependent but also clearly influenced by tumor burden, indicating a need for individualization of therapy. 89Zr-trastuzumab PET-imaging detected not only known tumor lesions in the liver, lung, bone and brain but also unknown brain and bone lesions were detected. The mean relative tumor uptake(± SD) in liver, bone and brain lesions was respectively 13.0±5.2, 4.2±1.5 and 3.5±4.2, while mean relative tissue uptake in normal liver, spleen, kidneys and brain was respectively 6.1±2.3, 2.7±0.8, 3.8±1.0 and 0.19±0.11. Conclusions: HER2-PET imaging with 89Zr-trastuzumab shows excellent tumor tracer uptake and can be used to detect HER2 positive breast cancer metastases and to quantify 89Zr-trastuzumab uptake, non-invasively. Patients on trastuzumab can be imaged with 37 MBq 89Zr-trastuzumab at a protein dose of 10 mg trastuzumab while trastuzumab naive patients require 50 mg. No significant financial relationships to disclose.
Estrogen receptor expression and docetaxel efficacy in patients with metastatic breast cancer: A pooled analysis of four randomized trials
Authors: Mazouni C. , André F. , Broglio K. , Pusztai L. , Hortobagyi G. N. 
Published: August 2020

1046 Background:Differences in the efficacy of various chemotherapies in patients with estrogen receptor (ER) positive metastatic breast cancer are not well understood. In the present study, we assessed the efficacy of docetaxel in patients with metastatic breast cancer according to ER expression.Methods: The efficacy of docetaxel on response rates and progression-free survival were analyzed according to ER expression in four randomized trials that included a total of 1,631 patients. Odds-ratio for tumor response was estimated with logistic regression and hazard ratio for progression-free survival was estimated with Cox proportional hazards models. Results: ER expression was assessable in 1,037 patients included in these trials (64%). ER was expressed in 601 tumors (58%). Overall, docetaxel was associated with an increased response rate (odds ratio: 2.66, 95% CI: 1.83 to 3.87) and decreased hazard of disease progression (hazard ratio: 0.85, 95% CI: 0.73 to 0.97) compared to non-docetaxel containing therapy. Docetaxel was associated with similar improvement in response rate both in patients with ER-positive (odds ratio: 2.90, 95% CI: 1.72 to 4.87) and ER-negative disease (odds ratio: 2.55, 95% CI: 1.44 to 4.51). Among all ER-positive patients, tumor response rate was 31.1% among patients who did not receive docetaxel and 46.8% among patients who did receive docetaxel. Decreased hazard of disease progression due to docetaxel was also similar in ER-positive (HR: 0.82, 95% CI: 0.67–1.00) and ER-negative cancers (HR: 0.86, 95% CI: 0.70–1.07), but these results were heterogeneous among trials. The effect of docetaxel was not different in ER-positive and ER-negative disease, both in terms of response rates and progression-free survival (interaction test, p = 0.77 and p = 0.93). Conclusions: Docetaxel increases response rates and decreases the risk of disease-progression in a statistically similar extent both in patients with ER-positive and ER-negative metastatic breast cancer. No significant financial relationships to disclose.
Anthracycline-rechallenge using pegylated liposomal doxorubicin (PLD) in previously treated patients with metastatic breast cancer (MBC): A meta-analysis using pooled individual data from four prospective trials
Authors: Al-Batran S. , Scholz M. , Jäger E. 
Published: August 2020

1047 Background: Few data are available on the efficacy of anthracycline rechallenge using PLD. Methods: Pooled individual data from 4 prospective trials (Keller, J Clin Oncol. 2004; O'Brien, Ann Oncol. 2004; Al-Batran, Br J Cancer. 2006; and Al-Batran, Oncology. 2006) were utilized to evaluate the activity of PLD in pts with MBC previously treated with conventional anthracyclines. Primary endpoint was clinical benefit rate (CBR), defined as objective response or stable disease, both lasting ≥ 6 months. CBR was assessed in the entire group (primary hypothesis CBR ≥ 30%) and in pre-defined subgroups of pts depending on the most important features of their prior anthracycline-based therapy. Results: The studies comprised a total 935 pts, of whom 274 pts had received PLD after prior exposure to conventional anthracyclines. At the time of PLD therapy, these (274) pts were heavily pre-treated for MBC (median lines of previous chemotherapy 4, range 1 to 9, and 93.4% of pts received PLD after ≥ 2 previous chemotherapies for MBC). Prior anthracycline treatment was adjuvant, anti-metastatic, or both in 14%, 46%, or 40% of pts, respectively. The overall CBR from PLD was 32.2% (95% CI, 26.7%-37.8%), with no difference between pts who were considered anthracycline resistant (based on the study records) and those who were not (31.9% vs. 31.6%, respectively; p = 1). There was also no difference in CBR from PLD between pts who received prior anthracyclines adjuvant only (33.3%), anti-metastatic only (34.4%) or both (29.4%; p = 0.71). There was a trend towards a higher CBR in pts who received PLD at > 12 months vs ≤ 12 months since the end of their prior conventional anthracycline treatment (34.2% vs. 26.3%, respectively; p = 0.21). Higher CBR (up to 47%) and longer survival times were observed in pts without taxane pretreatment or with a low number of previous chemotherapies, most likely reflecting a less advanced disease in these pts. Conclusions: This meta-analysis demonstrates a clinical benefit from PLD in MBC pts previously treated with multiple chemotherapies, including anthracyclines. Interestingly, the CBR was independent of resistance to, setting of, or time since previous conventional anthracycline therapy. [Table: see text]
A SARC global collaborative phase II trial of R1507, a recombinant human monoclonal antibody to the insulin-like growth factor-1 receptor (IGF1R) in patients with recurrent or refractory sarcomas
Authors: Patel S. , Pappo A. , Crowley J. , Reinke D. , Eid J. , Ritland S. , Chawla S. , Staddon A. , Maki R. , Vassal G. , Helman L. 
Published: August 2020

10503 Background: The IGF1 system has been implicated in sarcoma development and inhibition of IGF1R function has been shown to induce clinical responses in select sarcomas. Methods: Objectives included response rate (RR) and progression-free survival (PFS) to R1507 in patients with recurrent or refractory Ewing's (ES, 2 cohorts- primary refractory vs. others) osteo (OS), synovial (SS), rhabdomyosarcoma (RMS), and other sarcomas. Eligibility included recurrent/refractory measurable disease, age ≥ 12 yrs, life expectancy ≥ 6 weeks, Karnofsky PS ≥ 70, adequate renal, hepatic and bone marrow function. R1507 was administered i.v. at 9 mg/kg over one hour weekly. Response was assessed by WHO criteria every 6 wks X 4 and every 12 wks thereafter. A two-stage design (Green and Dahlberg) was used. The endpoint for the primary refractory ES cohort was PFS at week 18 (planned n=65). RR was the primary endpoint for the remaining cohorts (planned n=240). Results: From 12/07–12/08, 203 eligible patients from 29 centers across the US, Europe and Australia were enrolled. Age ranged from 12–85 yrs (median=27 yrs) and 126 were male. Verified histologic subtypes were ES (n=71), OS (n=43), RMS (n=28), SS (n=25), and others (n=25). 15 severe adverse events were reported in 9 patients, the most common being fatigue (n=2), thrombocytopenia (n=2), dehydration (n=2), and hyperglycemia (n=2). Clinically significant activity has been observed in ES, RMS and OS with several dramatic responses seen in ES and RMS. Independent radiologic review is currently ongoing and updated data will be presented. Conclusions: The rapid accrual amongst many centers in diverse geographical locations demonstrates the feasibility of collaborative research in sarcomas. R1507 is well tolerated and a promising new agent for the treatment of various sarcomas. SARC and Roche are collaborating in additional clinical trials to better define the role of R1507 in the treatment of selected sarcomas. [Table: see text]