bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of childhood glial tumors with cisplatin and irinotecan
Authors: Mora J. , Cruz O. , Parareda A. , Guillen A. , Puy R. , Massaguer S. , de Torres C. , Garcia G. , Costa J. M. 
Published: August 2020

10062 Background: Childhood glial tumors are heterogeneous neoplasias for which non-surgical management is controversial. After a pilot study suggesting that irinotecan/cisplatin (I/C) may be effective in children (Mora et al, Neuro Oncol 2007), we initiated a phase II prospective trial with the aim of avoiding radiation therapy for low grade's (LG) and improve outcome for high grade's (HG). Methods: The indication for adjuvant therapy was based upon histology, the extent of surgical resection, and the presence of clinical or neuroradiological signs of progression. Weekly Irinotecan (50 mg/m2 and 65 mg/m2 the last 2 cycles) and Cisplatin (30 mg/m2) for four consecutive weeks (1 cycle), and a total of 4 cycles was used. Results: From January 2004 to December 2007, 30 children aged 6 months to 17 years were treated, 21 at diagnosis, 7 at progression and 2 at relapse. Fourteen tumors were WHO grades I-II gliomas (LGG), 10 grade III (6 gliomas, 2 anaplastic ependymomas and 2 AT/RT), and 6 had no biopsy (3 brainstem (BST) and 3 optic-pathway tumors (OPT)). Two patients had type-1 neurofibromatosis and OPT. Primary sites included: 4 supratentorial, 8 BST, 9 OPT, 2 cerebellar, and 7 spinal. Prior to the I/C regimen, gross total resection was performed in 7 and biopsy in 14 tumors; 9 patients received chemotherapy and 5 radiotherapy. All but 6 patients, 2 because of C allergy and 4 BST because of progression, completed the protocol, with no grade 3–4 side effects. Vomiting was the main side effect. Twenty (90%) of 22 patients with evaluable clinical symptoms had a complete and rapid response, with objective functional recovery. With a median follow-up of 25 months, 14 (47%) patients had a complete/partial response (7 out of 10 HG), 10 (40%) had stable disease (8 out of 14 LG), and 6 (20%) progressed (all BST). Five patients died of disease, all BST. Twenty-five (83%) patients remain progression-free, median 27 months from protocol entry. Conclusions: Seventy percent objective response rate for HG and avoidance of radiotherapy for 93% of LG was obtained using the I/C regimen. Remarkable fast clinical responses and functional recoveries occurred. No significant financial relationships to disclose.
Off-label drug use in women with breast cancer
Authors: Dean-Colomb W. , Fang S. , Smith W. , Michaud L. , Hortabagyi G. N. , Giordano S. 
Published: August 2020

1016 Background: Despite reports of widespread use of off-label agents in cancer treatment, little is known about the off-label use of agents in the treatment of breast cancer patients. Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) - Medicare linked database to identify 2082 persons older than 65 years who were diagnosed with distant stage breast cancer between 1991 and 2002 and who were treated with chemotherapy between diagnosis and death. Off versus on-label classification was based upon FDA-approved indication in the treatment of breast cancer. We calculated the percentage of patients receiving off-label chemotherapy and used multivariate logistic regression models to estimate predictors of off-label chemotherapy use. We also evaluated the appropriateness of off-label chemotherapy drugs using DRUGDEX classifications. Results: Overall, 34.9% of patients were treated with off-label chemotherapy drugs. Of the thirty-six agents that were used to treat these patients, only 8 (22%) were FDA-approved for use in the treatment of breast cancer. Off-label use was least common in patients age 80 years and older (OR 1.93, 95% 1.35–2.76 for 80+ vs. 66–70 years) and varied by diagnosis year and geographic region. The most commonly used off-label agents were vinorelbine and gemcitabine, with 16.0% and 8.4% of patients receiving these agents, respectively. While 71% of the drugs used off-label lacked supporting evidence for their use in the treatment of breast cancer, these drugs were used in a small number of patients. Only 6.7% of patients were treated with drugs considered inappropriate for use in the treatment of breast cancer. Conclusions: Off-label chemotherapy use is widespread among patients with metastatic breast cancer. However, the majority of patients who received off-label chemotherapy received drugs with scientific data supporting such use. No significant financial relationships to disclose.
Use of BIBW 2992, a novel irreversible EGFR/HER2 tyrosine kinase inhibitor (TKI), to treat patients with HER2-positive metastatic breast cancer after failure of treatment with trastuzumab
Authors: Hickish T. , Wheatley D. , Lin N. , Carey L. , Houston S. , Mendelson D. , Solca F. , Uttenreuther-Fischer M. , Jones H. , Winer E. 
Published: August 2020

1023 Background: BIBW 2992 (Tovok) is an oral, novel, and potent, irreversible dual epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) inhibitor, with preclinical activity in trastuzumab-resistant cell lines overexpressing HER2 and phase I clinical activity. A phase II study of BIBW 2992 in patients with HER2-positive breast cancer who have failed treatment with trastuzumab is currently being conducted in the US and the UK. Methods: This is a multi-institutional open label single arm phase II study, planning to recruit 40 patients. Eligibility criteria include stage IIIB or IV HER2-positive metastatic breast cancer, progression following receipt of trastuzumab or intolerance of trastuzumab, measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 and adequate organ function. Patients receive 50 mg BIBW 2992 once daily until disease progression. Tumor assessments are performed every two courses (one course = 28 days). The primary endpoint is objective response rate (RECIST criteria). Safety data are also collected. Results: To date, 40 patients have started treatment on the trial. Patients had received a median of three lines of prior therapy. Nine patients discontinued treatment prior to the first assessment at 8 weeks; four due to disease progression, four due to adverse events and one due to withdrawal of consent. Twenty-one patients have had tumor assessment after 8 weeks of treatment. Of these, four patients had a partial response (PR) and 10 patients had stable disease (SD). The PR has been confirmed at 16 weeks in one patient. The most frequently observed side effects to date are rash (Common Toxicity Criteria for Adverse Events [CTCAE] grade 3 in 4 patients) and diarrhea (CTCAE grade 3 in 8 patients). There were 20 dose reductions in 17 patients. Conclusions: BIBW 2992 at 50 mg/day induced responses and seems promising in HER2-positive breast cancer patients who have failed treatment with trastuzumab. Manageable cutaneous adverse events and diarrhea were the main side effects. [Table: see text]
α-basic-crystallin expression in basal-like breast cancer and its association with brain metastasis
Authors: Kennecke H. F. , Voduc D. , Leung S. , Cryns V. L. , Perou C. M. , Nielsen T. O. , Cheang M. 
Published: August 2020

1025 Background: Basal-like breast cancers are high grade tumors with poor prognosis, having propensity for brain and lung metastasis (Perou et al. Nature 406:747–52, 2000, Cheang et al. Clin Cancer Res 14:1368–76, 2008, Luck et al. Clin Oncol (R Coll Radiol) 20:40–5, 2008). α-basic-crystallin (αBC), a small heat shock protein with anti-apoptotic and oncogenic activity, is expressed in about half of basal-like breast cancers but only 6% of other types (Moyano et al. J Clin Invest 116:261–70, 2006). Here we investigate the association of αBC with sites of distant metastasis in a large cohort of breast cancer patients. Methods: Our cohort consists of 4046 early invasive breast cancers referred to the British Columbia Cancer Agency from 1986 to 1992. Archival paraffin tissue blocks were used to construct tissue microarrays. Breast cancer subtypes were defined using a surrogate of six immunohistochemical markers: ER, PR, HER2, Ki-67, epidermal growth factor receptor and cytokeratin 5/6. αBC immunostaining was scored by pre-established, published criteria. All documented sites of distant metastasis were abstracted by chart review according to predefined categories. The null hypothesis was tested using chi-square and Fisher's Exact tests; all tests were two-sided. Results: Among 3,248 cases with interpretable αBC data, 11% were αBC +. Among patients who developed distant metastatic disease, the 10-yr BCSS survival in αBC+ and - tumors was 12% and 29%. Sites of metastatic disease included: brain (15%), lung (35%), liver (35%) and bone (65%). Brain metastasis was significantly more common among αBC positive tumors (Fisher's Exact test p<10e-8). Basal-like tumors with brain metastasis commonly co-expressed αBC (Chi-square p=0.006). Conclusion: αBC is significantly associated with brain metastasis, particularly among basal breast cancers. These findings suggested that αBC may be involved in tumor cell metastasis and may allow early identification of a subset of patients at particularly high risk of brain metastasis. [Table: see text] No significant financial relationships to disclose.
Bevacizumab and pegylated liposomal doxorubicin as first-line therapy for locally recurrent or metastatic breast cancer: A multicenter, single-arm phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)
Authors: Rochlitz C. , Spirig C. , Ruhstaller T. , Suter T. , Bühlmann M. , Fehr M. , Schönenberger A. , Lerch S. , Mayer M. , Zaman K. 
Published: August 2020

1030 Background: Bevacizumab in combination with taxanes has become a standard first-line treatment of advanced breast cancer in some countries, but there is no information on its use in combination with pegylated lipsomal doxorubicin in metastatic breast cancer. Therefore, we performed a multicenter, single-arm phase II trial to evaluate the toxicity and efficacy of pegylated liposomal doxorubicin (PLD) and bevacizumab (B) as first-line treatment in advanced breast cancer. Methods: PLD at a dose of 20 mg/m2 and B at 10 mg/kg were infused on days 1 and 15 of each 4-week cycle for a maximum of 6 cycles. Thereafter, B monotherapy was continued at the same dose until progression or toxicity. Primary endpoint was the occurrence of specific toxic events known to strongly interfere with quality of life, i.e., severe cardiac toxicity, any grade 4/5 toxicity, and selected grade 3 nonhematological toxicities (hand-foot-syndrome, cognitive disturbance, CNS hemorrhage, and mucositis/stomatitis). Secondary endpoints included overall response, progression free survival (PFS), time to treatment failure, and duration of response. Eligibility criteria included documentation of metastatic or inoperable breast cancer; measurable disease according to RECIST; erbB2-negativity; LVEF of ≥ 55%; WHO performance status 0 or 1. The study used a Herndon's two-stage design with 14 and 29 patients for stages 1 and 2, respectively. The promising rate of primary toxicity was <15% and the uninteresting rate >33%. The type I error probability was 5% and the power 80%. Results: The trial had to be stopped prematurely because of toxicity after the enrollment of 41 evaluable patients. Among these patients, 16 (39%) had grade 3 hand-foot syndrome, 1 grade 3 mucositis and 1 grade 4 cardiac toxicity. Thus, a total of 18/41 (44%, exact 95% c.i. 28–60%) of all patients had a primary toxicity. Best overall response rate was 23.3% (exact 95% c.i. 12–39%), median PFS was 7.5 months (95% c.i. 4.6–8.1 months). Conclusions: The combination of 2-weekly PLD and B in advanced breast cancer is surprisingly toxic and only modestly active and should not be further investigated. [Table: see text]
Safety and efficacy of first-line bevacizumab (B) plus chemotherapy (CT) for locally recurrent or metastatic breast cancer (LR/mBC): Analysis of MO19391 according to CT
Authors: Pierga J. , Pritchard K. I. , Thomssen C. , Cortes-Funes H. , Biganzoli L. , Padrik P. , Zvirbule Z. , Smith I. 
Published: August 2020

1033 Background: Combination of B with first-line paclitaxel (TP) or docetaxel (TD) significantly improves PFS vs taxane alone in pts with LR/mBC. The open-label, multicenter MO19391 trial further assessed safety and efficacy of first-line B plus a taxane in >2,000 pts in routine clinical practice. Methods: Eligible pts had HER2- negative LR/mBC (or HER2-positive LR/mBC progressing after trastuzumab-containing therapy), ECOG PS 0–2, no prior CT for LR/mBC and no evidence of CNS metastases. Pts received B 10mg/kg q2w or 15mg/kg q3w plus the physician's choice of taxane (TP or TD alone or with another CT) or other non-anthracycline CT according to physician's standard of care. Treatment was continued until disease progression, unacceptable toxicity, or refusal. The primary endpoint was safety (NCI CTCAE v3.0); secondary endpoints included TTP, OS, and safety in pts developing CNS metastases. Results: From Sept 2006 to June 2008, 2,027 pts from 37 countries were enrolled. Median follow-up is 7.4 months. CT included a taxane (alone or with CT) in ∼75% of pts. Non-taxane agents included capecitabine (X) and vinorelbine (V). In the overall population, median age was 54 years (range 21–93), 70% were ER and/or PgR positive, and 32% had disease-free interval (DFI) ≤24 months. Baseline characteristics were broadly similar across subgroups. However, the X monotherapy subgroup included fewer pts with >3 metastatic lesions and more with a DFI ≤24 months and/or triple-negative disease compared with other subgroups. Safety and efficacy results grouped by CT are shown below. OS data are still immature (85% of pts alive at this analysis). Conclusions: In this large phase IV study, safety and efficacy of B plus TP or TD was similar to results of E2100 and AVADO. Variations in toxicities were consistent with the known profiles of each CT and no new safety signals for B were observed. The lowest incidences of serious Aes were seen with B plus TP or X. TTP was shorter with X and non-taxane combinations. Such findings are potentially attributable to small pt numbers and differences in baseline characteristics. These results show that B can be safely and effectively combined with a wide range of commonly used CT regimens as first-line therapy for mBC. [Table: see text] [Table: see text]
Outcomes of first-line chemotherapy for advanced breast cancer in women with good versus poor quality of life at baseline
Authors: Lee C. , Stockler M. , Gebski V. , Coates A. , Simes R. J. 
Published: August 2020

1036 Background: Health-related quality of life (QL) is an established predictor of outcome in advanced breast cancer. The benefits and harms of chemotherapy in women with poor QL are unclear. Methods: We used data from 378 women receiving classical CMF in the control arms of 3 randomized trials. QL was rated at baseline by patients with linear analogue self-assessment scales (LASA) for physical well-being (PWB), mood, appetite, pain, nausea/vomiting, and overall QL; and by physicians with Spitzer's Quality-Of-Life Index (QL-I). Patients were divided into 3 groups according to their baseline QL scores: good (LASA 0–25, QL-I 5–7), intermediate (LASA 26–65, QL-I 8–10) or poor (LASA 66–100, QL-I 11–15). The main outcomes were overall survival (OS), progression-free survival (PFS), objective tumor response (OTR = CR or PR), weight loss, and grade 3 or 4 adverse events (AE). Results: All aspects of QL, except nausea/vomiting, were significant univariable predictors of OS and PFS. PWB, mood, appetite and QL-I were independently significant predictors of OS in a multivariable model with biomedical factors. Only patient's self-rated poor QL had lower rates of OTR, and higher rates of nonhematological AE than those with good QL (see Table), but rates of hematological AE were similar. Weight loss occurred more frequently in those with poor appetite (OR 5.8, p=0.05) or poor PWB (OR 4.9, p=0.05). Conclusions: Less than 25% of women with poor baseline QL responded to first line CMF but over 25% had severe non-hematological toxicity. Baseline QL predicts these outcomes beyond biomedical factors. [Table: see text] No significant financial relationships to disclose.
The association of metabolic syndrome with triple-negative breast cancer
Authors: Maiti B. , Kundranda M. N. , Jin T. , Spiro T. P. , Daw H. A. 
Published: August 2020

1038 Background: Metabolic syndrome, a conglomerate of obesity, insulin resistance, hypertriglyceridemia, low HDL (high density lipoprotein), and hypertension is associated with an increased risk of breast cancer. However, no clear association has been shown between the highly aggressive triple-negative breast cancer and metabolic syndrome. Methods: In a retrospective review we compared triple-negative and non-triple-negative breast cancer cases for the presence of metabolic syndrome by NCEP (National Cholesterol Education Program) or AACE (American Association of Clinical Endocrinologists) definitions. Data on metabolic syndrome criteria, tumor size, grade, lymph node status, and ductal carcinoma in situ (DCIS) were reviewed. Chi-square test or Student's t-test was used for data analysis. Results: The entire cohort of 176 patients (12.5% African-American) with median age 56.5 years (range 26–91 years) comprised of 86 triple-negative cases and 90 non-triple-negative cases. A statistically significant association of triple-negative breast cancer with metabolic syndrome was observed. According to the NCEP criteria 58.1% of triple negative patients had metabolic syndrome as compared to only 36.7% of non-triple negative patients (p = 0.004). Consistently, by the AACE criteria 52.3% of triple negative patients had metabolic syndrome as compared to 34.4% of non-triple negative patients (p = 0.017). Contrary to blood glucose, triglyceride, or HDL levels, which independently showed significant association with triple-negative breast cancer, hypertension, or BMI showed no independent association. Additionally, triple-negative tumors displayed a significantly higher histologic grade and relative paucity of ductal carcinoma in situ (DCIS) when compared to the non-triple negative tumors (p < 0.001). Conclusions: The data suggests that the metabolic syndrome is significantly more prevalent in triple-negative breast cancer patients when compared to the non-triple-negative patients. Additionally, triple-negative breast cancer showed a significantly higher histologic grade and a relative absence of DCIS. Whether the presence of metabolic syndrome preferentially increases the risk of developing triple-negative-breast cancer needs to be elucidated by future prospective studies. No significant financial relationships to disclose.
Clinical benefit of lapatinib-based therapy in patients with HER2-positive breast tumors expressing p95HER2
Authors: Prudkin L. , Aura C. M. , Jimenez J. , Scaltriti M. , Ellis C. , Gagnon R. , Arbushites M. , Liu Y. , Koehler M. , Baselga J. 
Published: August 2020

1048 Background: Approximately 25% of HER2 overexpressing breast tumors express a truncated form of the receptor (p95HER2) that lacks the extracellular domain but retains kinase activity. p95HER2-positive tumors are associated with a worse prognosis and resistant to trastuzumab therapy. In preclinical models, lapatinib (L), a tyrosine kinase inhibitor of EGFR and HER2, is active in p95HER2 expressing tumors. The aim of this analysis was to test the hypothesis that benefit from L-based therapy is independent of p95HER2 expression in 2 clinical trials in patients (pts) with HER2-positive tumors treated with either L monotherapy (Study EGF20009 ) or L in combination with capecitabine (Study EGF100151). Methods: Pre-treatment tumor tissue from both trials (N=201) was analyzed for p95HER2 expression by immunofluorescence as previously described (Scaltriti M. et al, JNCI 2007). Expression of p95HER2 was correlated with clinical benefit rate (CBR: complete response [CR] + partial response [PR] + stable disease [SD] ≥ 24 weeks) and progression-free survival (PFS) using logistic regression and Cox-proportional hazard models. Results: 68/105 and an initial 72/96 tissue samples were evaluable for p95HER2 expression from studies EGF20009 and EGF100151, respectively. The Table summarizes the results from the L treated pts. The CBR and PFS in L treated pts were not significantly different between the p95HER2 subgroups. Expanded data for p95HER2 expression in additional EGF100151 tumor samples will be presented. Conclusions: L as a monotherapy or in combination with capecitabine has similar response activity in pts with p95HER2-positive and p95HER2-negative HER2-positive breast tumors. [Table: see text] [Table: see text]
First-line treatment with lapatinib plus paclitaxel versus paclitaxel alone for patients with HER2+ metastatic breast cancer (MBC): Quality-of-life (QOL) analysis using repeated measures and pattern mixture models
Authors: Sherrill B. , Wu Y. , Amonkar M. , Arbushites M. , DiLeo A. 
Published: August 2020

1049 Background: A phase III randomized, multicenter, double-blind, placebo-controlled study compared first-line therapy with lapatinib and paclitaxel (L+P) versus paclitaxel alone (P) for MBC. In a sub-group analysis of HER2+ patients, time to tumor progression for L+P was significantly improved, with an emerging trend for survival benefit. This analysis models the QOL data in the subset of the randomized ITT population that overexpressed HER2 (FISH+ or IHC3+). Methods: QOL was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. Outcome measures included FACT-B total score, trial outcome index (TOI) score and breast cancer subscale (BCS). Higher scores represent better QOL. Patients completed the FACT-B at the screening visit, week 9, every 12 weeks thereafter, and at discontinuation of therapy. The assessment at discontinuation was applied to the next scheduled visit for analyses. Changes from baseline were analyzed using repeated measures models with baseline score as a covariate. Pattern mixture modeling was implemented as a sensitivity analysis. Results: Of 579 randomized patients, 86 were HER-2+ and 85 completed at least one item from the FACT-B (n = 48 L+P; n = 37 P). The baseline characteristics of this subset were well-matched with regard to age, ECOG status, and prior anthracycline use. More patients in the L+P group than in the P group had visceral disease (69% vs 51%) and more were at stage IV (88% vs 78%).Over the first year, the L+P arm demonstrated stable FACT-B scores over time, whereas average scores for patients on paclitaxel monotherapy decreased (change from baseline: L+P p = 0.99; P p = 0.01). Statistically significant differences were observed between treatment arms on the FACT-B (p = 0.05), TOI (p = 0.03), and BCS (p = 0.01). Pattern mixture models suggested more QOL differentiation between treatments among patients who progressed or withdrew within 6 months of study start. Conclusions: Among patients with HER2+ MBC, treatment with L+P resulted in more stable QOL than with P monotherapy. These findings represent clinically important differences between treatment groups. [Table: see text]