bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel in patients with HER2-positive metastatic breast cancer in the CLEOPATRA study.
Authors: Ewer Michael , Baselga José , Clark Emma , Benyunes Mark , Ross Graham , Swain Sandra M. 
Published: March 2020

533^ Background: Addition of trastuzumab (T) to chemotherapy has transformed outcomes in pts with HER2-positive breast cancer. In pts who had received anthracyclines (A), T has been associated with cardiac dysfunction. Monitoring cardiac tolerability of anticancer drugs is important, including that of a new regimen combining T with a second anti-HER2 antibody that inhibits HER2 dimerization, pertuzumab (P). In CLEOPATRA, efficacy and safety of P+T+docetaxel (D) were studied in HER2-positive 1st-line MBC (Baselga 2012). Methods: CLEOPATRA, a randomized, double-blind, placebo-controlled, ph III trial, enrolled 808 pts; 804 were included in the safety population. A baseline (BL) LVEF ≥50%, no history of congestive heart failure, and no LVEF decline to <50% during/after prior T were required. Treatment was administered q3w until disease progression or unmanageable toxicity (P/placebo [Pla]: 840 mg, followed by 420 mg; T: 8 mg/kg, followed by 6 mg/kg; D [≥6 cycles recommended]: 75 mg/m2, escalating to 100 mg/m2 if tolerated). LVEF was assessed by ECHO or MUGA at BL, every 9 wks during treatment, at discontinuation, and up to 3 yrs thereafter. Adverse events (AE) were monitored continuously and graded according to NCI-CTCAE v3.0. Results: The incidence of any cardiac disorder (grade ≥1) as assessed by the investigators was similar with Pla+T+D (16.4%) and P+T+D (14.5%). LVSD (grade ≥1) was the most frequent cardiac AE and more common with Pla+T+D. At the time of data cutoff for this analysis, 8/11 symptomatic LVSD events had resolved; none fatal. All pts who developed symptomatic LVSD had ≥1 potential cardiac risk factor (prior A, prior T, radiation, smoking, diabetes, hypertension, other). Compared to the overall pt population, only prior A and radiation were higher in pts who developed symptomatic LVSD. Conclusions: CLEOPATRA provides evidence that P+T+D does not increase overall cardiac disorders, specifically symptomatic LVSD, compared to Pla+T+D. [Table: see text]
BOLERO-2: Health-related quality-of-life in metastatic breast cancer patients treated with everolimus and exemestane versus exemestane.
Authors: Beck J. Thaddeus , Rugo Hope S. , Burris Howard A. , Baselga José , Noguchi Shinzaburo , Gnant Michael , Pritchard Kathleen I. , Bennett Lee , Ricci Jean-Francois , Hortobagyi Gabriel N. 
Published: March 2020

539 Background: BOLERO-2, a phase III study, randomized 724 patients with hormone-receptor–positive metastatic breast cancer, who had recurrence or progression on/after prior nonsteroidal aromatase inhibitor therapy, to everolimus (EVE) plus exemestane (EXE) or EXE and placebo. A preplanned 12-month median time interim analysis demonstrated that EVE+EXE significantly improved progression-free survival (PFS) vs EXE+placebo but that EVE+EXE resulted in a higher rate of grade 3/4 toxicity. Per-protocol patient reported health-related quality-of-life (HRQoL) data are limited; here we report on additional post-hoc analyses of these outcomes. Methods: Using the EORTC–QLQ‑C30 questionnaire, HRQoL was assessed at baseline and every 6 weeks thereafter until progression. The QLQ‑C30 consists of 30 items combined into 15 subscales, including a Global Health Status (GHS) where higher scores (range 0 to 100) indicate better HRQoL. This analysis included a protocol-specified time to definitive deterioration (TTD) analysis at a 5% decrease in QoL relative to baseline, with no subsequent increase above this threshold. We report additional sensitivity analyses using 10-point minimally important difference (MID) decreases in QLQ‑C30 score relative to baseline. Treatment arms were compared using a stratified logrank test and a Cox proportional hazards model adjusted for trial stratum (visceral metastases and previous hormone sensitivity), age, sex, race, baseline score and ECOG performance status, prognostic factors, and treatment history. Results: Baseline QLQ‑C30 GHS scores were not statistically significantly different across treatment groups (64.7 vs 65.3; difference -0.7 [95% CI; -4.3, 3.0]). The median TTD in HRQoL was 7.0 months (95% CI; 5.6, 8.3) for EVE+EXE vs 5.6 (95% CI; 4.2, 7.0) for EXE (P = .0792). Adjusted HR (0.80) approached significance (95% CI; 0.63, 1.02). At the 10-point MID, median TTD for EVE+EXE was 9.7 months (95% CI; 8.3, 11.2) vs 8.4 months (95% CI; 6.3, 12.5) for EXE. Adjusted HR was 0.90 (95% CI; 0.69, 1.18). Conclusions: These additional analyses demonstrate that in addition to significantly improving PFS, EVE+EXE does not compromise HRQoL.
BOLERO-2: Everolimus with exemestane versus exemestane alone in Asian patients with HER2-negative, hormone receptor-positive breast cancer.
Authors: Noguchi Shinzaburo , Masuda Norikazu , Ito Yoshinori , Iwata Hiroji , Mukai Hirofumi , Horiguchi Jun , Tokuda Yutaka , Kuroi Katsumasa , Iwase Hirotaka , Inaji Hideo , Ohsumi Shozo , Piccart-Gebhart Martine J. , Hortobagyi Gabriel N. , Rugo Hope S. , Gnant Michael , Campone Mario , Sahmoud Tarek , Pritchard Kathleen I. , Burris Howard A. , Baselga José 
Published: March 2020

540 Background: Estrogen-receptor–positive (ER+) breast tumors can become refractory to aromatase inhibitor (AI) therapy. The mTOR pathway plays a critical role in hormone-resistant advanced breast cancer (ABC). Accordingly, the addition of everolimus (EVE) to exemestane (EXE) was evaluated in an international, phase III study (BOLERO-2) in patients with ER+ aBC refractory to letrozole or anastrozole. This report presents updated analyses from the population of Asian patients enrolled in this study. Methods: Eligible patients were randomized (2:1) to EXE (25 mg/day) with EVE (10 mg/day) or with matching placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, quality of life, and safety. Results: EVE + EXE significantly improved PFS versus EXE alone (HR = 0.44; 95% CI, 0.36-0.53; P < .0001) in the overall study population at median follow-up of 12.5 months. Of 143 patients of Asian origin (n = 106; 74% Japanese) enrolled in this study, 98 received EVE + EXE and 45 received EXE + placebo. At the time of database lock, 55 Asian patients (56%) in the combination arm had experienced disease progression compared with 34 patients (76%) in the EVE + placebo arm. Combination therapy reduced the risk of disease progression versus EXE alone by 44% among Asian patients (HR = 0.56; 95% CI, 0.37-0.87; P < .05). Commonly reported adverse events in the combination arm were consistent with previous clinical studies of mTOR inhibitors and included stomatitis (80%), rash (49%), dysgeusia (31%). Adverse events that occurred more frequently in the Asian subset versus Caucasians included stomatitis (80% vs 54%) and rash (49% vs 37%), whereas dyspnea (8% vs 24%) and asthenia (1% vs 17%) occurred less frequently in the Asian subset versus Caucasians. Conclusions: The addition of EVE to EXE significantly prolonged PFS in Asian patients versus EXE alone. Adverse events were higher in the combination arm but generally manageable. Combining EVE with an AI is a safe and effective treatment option for Asian women with non-steroidal AI resistant/refractory ER+ ABC.
Response pattern in 844 patients with infiltrating lobular carcinoma (ILC) of the breast after neoadjuvant chemotherapy.
Authors: Pirvulescu Cristina , Loibl Sibylle , Von Minckwitz Gunter , Mau Christine , Blohmer Jens U. , Costa Serban Dan , Eidtmann Holger , Fasching Peter A. , Gerber Bernd , Untch Michael 
Published: March 2020

541 Background: Patients (pts) with infiltrating lobular carcinoma (ILC) have a different response to neoadjuvant chemotherapy compared to patients with non-lobular carcinoma (NLC). The aim of our analysis was to characterize correlates of the outcome impact of neoadjuvant chemotherapy in ILC and to compare those with NLC. Methods: Between 1998 and 2006; 6377 breast cancer patients were enrolled to 7 randomized neoadjuvant chemotherapy trials in Germany. For 6205 (98.3%) pts the histological type was available. 844 (13.6%) were classified as ILC, 5361 (86.4%) were classified as NLC. Endpoints of the analyses were: pathological complete response (pCR) defined as no invasive and no in-situ residuals in the breast and the lymph nodes, type of surgery, disease-free (DFS), local recurrence (LRFS) and overall survival (OS). Results: ILC was associated with older age, larger tumor size, negative nodes, lower grading, and hormone receptor (HR) positivity (all p<0.0001). The majority of pts with ILC were HR positive (717 pts, 86.9%) and had G1-G2 tumors (603 pts, 78.6%). Patients with ILC had a significant lower pCR rate than pts with NLC (pCR 6.04% vs. 16.4%, p<0.001). In the ILC group, pts with HR positive, triple-negative and HER2-positive tumors had a pCR rate of 5%, 18.3% and 9.2%, respectively. One of 35 pts with G1 and HR positive ILC had a pCR. Breast conservation therapy (BCT) in pts with pCR was 72.5% in the ILC group and 85.5% in the NLC group (p<0.0001). Predictors for pCR in the multivariate analysis were for ILC: patient age, grading and HR status. ILC pts had a significantly longer LRFS compared to NLC pts (with or without pCR after neoadjuvant chemotherapy, mean 112 months 95%CI [109.7-115.7] vs. 106 months 95%CI [104.4-107.4], p=0.002). Conclusions: In patients with ILC age, grading and HR status were predictive for pCR. Pts with ILC have a more favourable outcome after neoadjuvant chemotherapy despite a significantly lower pCR rate compared to pts with NLC.
A prospective clinical utility study of the impact of the 21-gene recurrence score assay (Oncotype DX) in estrogen receptor positive (ER+) node negative (pN0) breast cancer in academic Canadian centers.
Authors: Davidson James Ashley , Cromwell Ian , Ellard Susan , Lohrisch Caroline A. , Gelmon Karen A. , Shenkier Tamara Nina , Villa Diego , Lim Howard John , Sun Sophie , Taylor Sara Kristina , Taylor Marianne , Czerkawski Barbara , Hayes Malcolm , Ionescu Diana , Pope Janice , Berube Jayne , Yoshizawa Carl N. , Chao Calvin , Peacock Stuart , Chia Stephen K. L. 
Published: March 2020

549^ Background: The Oncotype DX 21-gene Recurrence Score assay (RS) can potentially predict the magnitude of chemotherapy benefit in patients with stage I-II, node-negative, ER+ disease who will be treated with tamoxifen for 5 years. While use in the United States has grown significantly since its introduction, it is not yet routinely ordered by oncologists in most parts of Canada. The primary purpose of this study was to measure the impact of the Oncotype DX test on the physician’s treatment recommendation in ER+ pN0 breast cancer in British Columbia. Methods: After providing informed consent, patients and medical oncologists completed respective pre-RS questionnaires indicating their treatment preferences and level of confidence and a decisional conflict scale (patients only). At a subsequent visit, after the RS result was known and discussed, the patient and oncologist completed a second set of questionnaires. The proportion of physician treatment recommendations that changed from baseline to follow-up (post RS) were calculated with 95% confidence interval (CI). A prospective health economic (HE) analysis was also performed. Results: From May 2010 to July 2011, two participating BCCA centres enrolled 156 patients. Of the 150 for whom successful RS assay results were obtained, physicians changed their chemotherapy recommendation in 45 cases (30%; 95% CI 22.8-38.0%); either to add (10%; 95% CI 5.7-16.0%) or omit (20%; 95% CI 13.9-27.3%) adjuvant chemotherapy. As a secondary end-point, in 84 cases (56%; 95% CI 47.7-64.1%) there was a change in either the planned chemo and/or endocrine therapy recommendation. There was an overall significant improvement in physician confidence post RS (p < 0.001). Patient decisional conflict also significantly decreased following the RS assay (p < 0.001). The HE analysis is ongoing and will be presented separately. Conclusions: Within the context of a publicly funded health care system, the RS assay significantly affects adjuvant treatment recommendations in ER+ node negative breast cancer, in addition to reducing patient decisional conflict.
Cilengitide with cetuximab, cisplatin, and 5-FU in recurrent and/or metastatic squamous cell cancer of the head and neck: The ADVANTAGE phase II trial.
Authors: Vermorken Jan Baptist , Peyrade Frederic , Krauss Juergen , Mesia Ricard , Remenar Eva , Gauler Thomas C. , Keilholz Ulrich , Delord Jean-Pierre , Schafhausen Philippe , Erfán Jozsef , Brummendorf Tim H. , Iglesias Lara , Bethe Ullrich , de La Bourdonnaye Guillaume , Clement Paul M. 
Published: March 2020

5516^ Background: Prognosis for patients with recurrent and/or metastatic squamous cell cancer of the head and neck (R/M-SCCHN) is very poor. αvβ5 integrin is overexpressed in SCCHN and selective integrin blockade is being investigated as a treatment strategy. Methods: ADVANTAGE was a phase I/II study evaluating cilengitide with cetuximab and platinum-based chemotherapy. Eligible patients were ≥18 years with ≥1 measurable lesion, Karnofski performance status ≥70%, and confirmed R/M-SCCHN. The phase II part reported herein was an open-label, randomized, controlled trial investigating progression-free survival (PFS) in patients treated with 2 cilengitide 2000 mg regimens: once weekly (CIL1W) and twice weekly (CIL2W) administration combined with cisplatin, 5-FU, and cetuximab (PFE) as compared with PFE alone (control). Secondary objectives included overall survival (OS) and objective response (OR). Treatment-emergent adverse events (TEAEs) were monitored. Results: 184 eligible patients were enrolled. Overall, patient characteristics were similar across arms. Median duration of treatments was shorter in the CIL2W arm compared with the CIL1W arm (cilengitide: 16.1 vs 23.4 wk, cetuximab: 16.0 vs 22.6 wk, platinum: 16.0 vs 18.0 wk, and 5-FU: 14.6 vs 18.0 wk). Median PFS was 6.4 months in the CIL1W group, 5.6 months in the CIL2W group and 5.7 months in the control group, with CIL1W and CIL2W having HRs of 1.03 (95% CI: 0.67–1.59) and 1.55 (95% CI: 0.99–2.43) vs control. The latter HR was possibly due to less compliance in the CIL2W arm. Median OS was 12.4, 10.6, and 11.6 months in the CIL1W, CIL2W, and control groups, respectively. ORs were observed in 46.8%, 26.7%, and 35.5% of patients in the CIL1W, CIL2W, and control arms, respectively. Most common (≥15%) grade 3/4 TEAEs were neutropenia, hypokalemia, leukopenia, stomatitis, and fatigue. No safety differences were noted between treatment arms. Overall, there were 7 drug-related TEAEs (2 in CIL1W, 2 in CIL2W, and 3 in control) leading to death. Conclusions: In this population, neither of the cilengitide-containing regimens was able to demonstrate a PFS benefit over PFE alone.
Differential expression of EGFR, HER2, P16, and high-risk (hr) HPV status in oropharyngeal (Or) and oral cavity (OC) squamous cell carcinoma (SCC).
Authors: Sudaka Anne , Saada Esma , Natale Romain , Poissonnet Gilles , Benezery Karen , Bozec Alexandre , Hebert Christophe , Dassonville Olivier , Peyrade Frederic 
Published: March 2020

5521 Background: We aimed to better characterize the expression of epidermal growth factor receptors family in Or and OC SCC and correlate it to hr HPV status and anatomoclinical features. Methods: In formalin fixed paraffin embedded tumor tissues, chromogenic in situ hybridization (CISH) was performed to detect hr HPV and immunohistochemistry to evaluate EGFR (positive score: 4 to 6), HER2 (0=negative, 1=positive) and P16 (positive score:≥70% labeled cells) expression. Baseline data were collected and analyze will be used. Results: Among 128 pts, 69 were tobacco users and 58 male. Median age at diagnosis was 61 y [23-95]. EGFR, Her2, P16 expression and hrHPV positivity were seen in 84 (65%), 12 (9%), 47 (37%) and 47 (37%) respectively. P16 signal was linked with absence of tobacco (31% vs. 72%, Pearson chi2 test: p<10-3), absence of alcohol (48% vs. 83%, p<10-3), Or site (53% vs. 76%, p=0.005), T1 (34% vs. 19%, p=0.06), N0 (52% vs. 23%, p=0.003), absence of nodal capsular rupture (85% vs. 68%, p=0.02), WHO grade 3 (37% vs. 68%, p=0.001), hr HPV detection (17% vs. 70%, p<10-3). Multivariate analysis confirmed the link between P16 expression and hr HPV CISH positivity (OR=0.05, CI 95% [0.01-0.21], p<10-3) , absence of tobacco (OR=9.2, CI 95% [2.1-40.7], p=0.03) and N0 (OR=0.2, CI 95% [0.04- 0.75], p=0.02). EGFR signal was linked with tobacco (31% vs 78%,p=10-3), alcohol (57% vs 81%, p=0.02), OC localization (77% vs 58%, p=0.03), well differentiated SCC (73% WHO grade 1-2 vs 56% grade 3, p=0.04), absence of hr HPV detection (74% vs 52%, p=0.01) and absence of P16 labeling (78% vs 44%, p<10-3). Multivariate analysis confirmed the link between EGFR positivity and tobacco (OR=0.32, CI 95% [0.1-0.9], p=0.03), alcohol (OR=9.5, CI 95% [1.2- 72.8], p=0.03) and OC localization (OR=0.3, CI 95% [0.1-1], p=0.05). HER2 signal was linked with alcohol (5% vs 18%, p=0.04), history of tobacco associated neoplasia (10% vs 0%, p=0.02), Or site (14% vs 2%, p=0.03) and who grade 3 (5% vs 14%, p=0.06). Her2 labeling was not associated with tobacco, sex, hr HPV detection, P16 positivity or EGFR one. Conclusions: Hr HPV associated SCC have a low expression of EGFR and are not associated with HER2 labeling.
ARIX: A randomized trial of acupuncture versus oral care sessions in patients with chronic radiation-induced xerostomia following treatment for head and neck cancer.
Authors: Simcock Richard , Fallowfield Lesley , Monson Kathryn , Solis-Trapala Ivonne , Parlour Louise , Langridge Carolyn I , Jenkins Valerie A 
Published: March 2020

5527 Background: Radiation induced xerostomia impairs quality of life of in head and neck cancer survivors. Prior small non-randomised studies suggest that acupuncture may alleviate symptoms. We report the first large randomised trial comparing 8 weeks of group acupuncture with oral care sessions as a control. Methods: 145 patients with radiation induced xerostomia>18 months were recruited from 7 UK Cancer centres. Subjects received standardised group sessions of oral care (OC) education and 8 sessions of weekly group acupuncture (A) in a randomised crossover design with a 4 week washout (Group One OC/A and Group Two A/OC). Acupuncture was standardised to a technique previously piloted (3 auricular points and two distal points bilaterally). Patients completed the EORTC QLQ H&N questionnaire at baseline and weeks 5, 9, 13, 17 and 21 in addition to rating 4 key dry mouth symptoms. The primary outcome was patient reported improvement in dry mouth symptoms. The statistical analysis was longitudinal based on logistic regression models and adjustment for potential carry over. Stimulated and unstimulated saliva was measured. Results: An improvement for 5/7 symptoms was noted following acupuncture. In Group One 24% showed improvement 8 weeks following A (19% after OC). In Group Two 26% reported improvement in severe dry mouth after A (14% after OC). The estimated OR of improved dry mouth 5 weeks after A compared to OC was 2.0 (p=0.031), after adjusting for effects of time, potential carry-over, centre and patient characteristics. The estimated odds ratios of improvement in severity of symptoms for A compared to OC were (OR=1.67, p=0.048) for sticky saliva, (OR=2.08, p=0.011) for needing to sip to swallow food and (OR=1.71, p=0.013) for waking up at night needing to drink. Mean attendance rate for A was 89% and 80% for OC. There was no significant change in saliva production over time or by intervention. Mean global QoL score did not change significantly over time either within or between groups. No adverse events were seen. Conclusions: Eight sessions of weekly group acupuncture provides significantly better relief of radiation induced xerostomia than group oral care education.
Cost-effectiveness of zoledronic acid (ZOL) in postmenopausal women with early breast cancer receiving adjuvant letrozole.
Authors: Xue Mei , Fishman Peter , Botteman Marc 
Published: March 2020

553 Background: In the ZO-FAST trial, postmenopausal women with early breast cancer and a bone mineral density (BMD) T-score ≥ –2 and receiving adjuvant letrozole (2.5 mg/day) were randomized to either immediate ZOL (4 mg/6 months) treatment (upfront ZOL) or to the same therapy but only when BMD T-score decreased to < –2 or fracture occurrence (delayed ZOL). After 60 months, upfront ZOL increased both BMD and disease-free survival (P < .05) relative to delayed ZOL. The present analysis assessed, from a US payer perspective, the cost effectiveness of upfront ZOL vs delayed ZOL in this population. Methods: A Markov state-transition model was developed to estimate the lifetime costs and quality-adjusted life-years (QALYs) for a hypothetical cohort of postmenopausal women with early breast cancer receiving letrozole with upfront or delayed ZOL. Consistent with ZO-FAST, patients were 57 years of age and breast cancer recurrence-free at baseline. Patients could progress over time to Local Recurrence, Contra-lateral Tumor, Distant Recurrence, or Death. Transition probabilities were derived from ZO-FAST, supplemented with literature. Costs and utilities were literature based. All outcomes were discounted 3% per year. Results: Compared to delayed ZOL, upfront ZOL resulted in better overall survival, disease-free survival, and QALYs, but at a higher cost (Table). In the base case, the incremental cost/QALY gained with upfront vs delayed ZOL was $7,967. In > 95% of 1,000 probabilistic sensitivity analysis runs, upfront ZOL costs less than $38,376/QALY gained. Conclusions: Upfront ZOL may increase survival and QALY and, at a cost per QALY well under the $50,000/QALY threshold, is very cost-effective in this population. [Table: see text]