bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS wild-type metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3).
Authors: Heinemann Volker , Fischer von Weikersthal Ludwig , Decker Thomas , Kiani Alexander , Vehling-Kaiser Ursula , Al-Batran Salah-Eddin , Heintges Tobias , Lerchenmueller Juergen , Kahl Christoph , Seipelt Gernot , Kullmann Frank , Stauch Martina , Scheithauer Werner , Hielscher Joerg , Scholz Michael , Mueller Sebastian , Schaefer Britta , Modest Dominik Paul , Jung Andreas , Stintzing Sebastian 
Published: February 2017

LBA3506 Background: In patients (pts) with KRAS, wild-type metastatic colorectal cancer (mCRC) a head to head comparison of anti-EGFR- and anti-VEGF-directed first-line therapy has not been reported with regard to the FOLFIRI backbone. The AIO KRK-0306 study was therefore designed as a randomized multicenter trial to compare the efficacy of FOLFIRI plus cetuximab to FOLFIRI plus bevacizumab in mCRC pts not pretreated for metastatic disease. Methods: Pts were randomized to FOLFIRI (Tournigand regimen) every two wks plus cetuximab (400 mg/m² day 1, followed by 250 mg/m² wkly = arm A) or bevacizumab (5 mg/kg every two wks = arm B). The intent-to-treat (ITT) population comprised all pts who had at least completed one application of therapy. While recruitment initially was independent of KRAS status, an amendment confined inclusion to KRAS wildtype (WT) tumors. Recruitment was completed in October 2012. The primary study endpoint was objective response rate (ORR, investigators read). Results: Among 735 pts of the ITT-population, KRAS-WT was identified in 592. Of these, 297 pts were randomized to arm A and 295 to arm B. Median age was 64 years, 66% of pts were male, and ECOG PS 0-1 was observed in 98% of pts. Median duration of treatment was 4.7 mo vs 5.3 mo, respectively. While in the ITT analysis, ORR was comparable in arms A vs B (62% vs 57%, odds ratio 1.249), a significant superiority was found for assessable pts in arm A. Median PFS of the ITT population was nearly identical (10.3 vs 10.4 mo, HR 1.04, p=0.69), however, overall survival (OS) showed a significantly better outcome in arm A vs arm B (28.8 vs 25.0 mo, HR 0.77, p=0.0164, 95% CI: 0.620-0.953). Sixty-day mortality was low in both arms (1.01% vs 2.71%). Conclusions: ORR was comparable between arms in the ITT analysis, but favored arm A in assessable pts. Significantly superior OS was observed in KRAS-WT patients receiving cetuximab plus FOLFIRI as first-line treatment. Clinical trial information: NCT00433927.
SAMIT: A phase III randomized clinical trial of adjuvant paclitaxel followed by oral fluorinated pyrimidines for locally advanced gastric cancer.
Authors: Yoshida Kazuhiro , Tsuburaya Akira , Kobayashi Michiya , Yoshino Shigefumi , Takahashi Masazumi , Takiguchi Nobuhiro , Tanabe Kazuaki , Takahashi Naoto , Imamura Hiroshi , Tatsumoto Naokuni , Hara Akinori , Nishikawa Kazuhiro , Fukushima Ryoji , Kurita Akira , Kojima Hiroshi , Miyashita Yumi , Oba Koji , Buyse Marc E. , Morita Satoshi , Sakamoto Junichi 
Published: February 2017

LBA4002 Background: Adjuvant chemotherapy with tegafur/uracil (UFT) used to be a tentative Japanese standard treatment and has been replaced by S-1 according to the result of the ACTS-GC trial, although there has been no direct comparison. Paclitaxel (PTX) has been widely used as one of the key drugs for unresectable GC. A randomized phase III trial with a two-by-two factorial design was planned to assess the survival benefit of sequential use of PTX and oral fluorinated pyrimidines (FPs) in comparison with FPs alone, and to compare UFT and S-1. Methods: Patients with serosa-invading GC who underwent R0/1 resection with extended (D2) lymph node dissection were randomized to receive either UFT 267mg/m2 daily (arm A), S-1 80mg/m2 daily for 2 weeks every 3 weeks (B), weekly PTX 80 mg/m2 followed by UFT (C), or PTX followed by S-1 (D) for 24 weeks. The primary endpoint was disease-free survival (DFS). 708 patients per groups were necessary to detect a hazard ratio of 0.8 with 90% power for superiority of the sequential arms, C+D, vs. A+B (two-sided 5.0% significance level). The number of patients was set to 370 per arm (total 1480) with an 88% power for noninferiority (1.33 as the margin) of UFT vs. S-1. Results: Between August 2004 and October 2007, 1,495 patients from 232 centers were randomized with the full analysis set of 1,433. Demographics were well balanced among arm A (n=359), B (n=364), C (n=355), and D (n=355); mean age was 64, 86% were PS 0, 68% of tumors were 8 cm or greater and 85% were clinically node positive. Grade 3-4 neutropenia or anorexia occurred in 11% or 6%, 13% or 7%, 13% or 2%, and 23% or 5% for arm A, B, C, and D, respectively. Other % grade 3-4 toxicities were less than 5%. Median follow-up was 1,875 days and 728 events occurred. Difference in DFS between C+D and A+B were not statistically significant (HR=0.92, 95%CI 0.80-1.07, p= 0.273). HR of A+C vs. B+D was 1.23 (95%CI 1.07-1.43) and hence the null hypothesis was not rejected. Conclusions: There was a trend for better DFS for sequential use of PTX followed by FPs. Comparison between the FPs demonstrated that UFT was inferior to S-1. Sequential PTX/S-1 is safe and effective for locally advanced GC in an adjuvant setting. Clinical trial information: C000000082.
Phase III trial of a 3-weekly versus 5-weekly schedule of S-1 plus cisplatin (SP) combination chemotherapy for first-line treatment of advanced gastric cancer (AGC): SOS study.
Authors: Ryu Min-Hee , Baba Eishi , Lee Kyung Hee , Boku Narikazu , Park Young Iee , Hyodo Ichinosuke , Nam Byung-Ho , Esaki Taito , Ryoo Baek-Yeol , Song Eun-Kee , Cho Sanghee , Lee Sung Sook , Kang Won Ki , Yang Sung Hyun , Zang Dae Young , Shin Dong Bok , Park Sook Ryun , Shinozaki Katsunori , Takano Toshimi , Kang Yoon-Koo ,   on behalf of SOS Investigators
Published: February 2017

LBA4024 Background: 5-weekly S-1 plus cisplatin (SP5: S-1 80-120 mg/body/day on D1-21, cisplatin 60 mg/m2 on D8, every 5 weeks) has become a standard first-line chemotherapy for AGC in Japan based on the SPIRITS trial (Lancet Oncol. 2008;9:215). To strengthen the low-dose intensity of cisplatin in this SP5 for greater efficacy, a 3-weekly S-1 plus cisplatin (SP3: S-1 80 mg/m2/day on D1-14, cisplatin 60 mg/m2on D1, every 3 weeks) has been developed in Korea (Cancer Chemother Pharmacol. 2008;61:837). Methods: This SOS study was a multicenter, randomized, open-label, phase III study to evaluate whether SP3 was non-inferior/superior to SP5 in terms of progression-free survival (PFS) determined by a blinded central radiology review according to RECIST v1.1. Patients (pts) with metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma and with no prior chemotherapy were randomized 1:1 to receive either SP3 or SP5 until disease progression or unacceptable toxicities. Results: Between February 2009 and January 2012, a total of 625 pts were randomized from 42 sites in Korea and Japan. Median age was 59.6 years. 99% of pts had ECOG performance status 0-1. 16% of pts had prior gastrectomy. 62% of pts had measurable lesions. With a median follow-up of 34.7 months (range, 14.2-48.8) in surviving pts, SP3 was significantly noninferior and superior to SP5 in PFS (median 5.5 months vs. 4.9 months; HR 0.82, 95% CI 0.68-0.99, p=0.0418). Overall response rate (ORR) was also better with SP3 than with SP5 (60% vs. 50%, p=0.029). However, OS of both groups was equivalent (median 14.1 vs. 13.9 months; HR 0.99, 95% CI 0.81-1.21, p=0.9068). Treatment was well tolerated in both arms, while SP3 was associated with more frequent G3/4 anemia (19% vs. 9%) and neutropenia (39% vs. 9%). Dose intensity was higher in SP3 than in SP5 for both agents (median 331 vs. 317 mg/m2/week for S-1, p<0.001; median 18 vs. 12 mg/m2/week for cisplatin, p<0.001). Conclusions: SP3 was noninferior and superior to SP5 in terms of PFS and ORR. However, considering the small benefit in PFS and no difference in OS, both SP3 and SP5 can be recommended for the first-line treatment of AGC. Clinical trial information: NCT00915382.
The breast cancer lifestyle intervention study.
Authors: Chun Jennifer , Friedman Erica Brooke , Schnabel Freya Ruth , Eddy Martha , Schwartz Shira , Kern Elizabeth , Kiely Deirdre , Guth Amber , Axelrod Deborah M. 
Published: February 2017

112 Background: Maintaining a healthy weight after breast cancer diagnosis has been associated with improved survival outcomes. Lifestyle interventions are particularly important in overweight women who are at an increased risk of overall and breast-cancer specific death compared to non-overweight women. The purpose of this study is to examine the barriers and acceptance of a lifestyle intervention program among overweight women with newly diagnosed breast cancer. Methods: The Breast Cancer Database of NYU Langone Medical Center was queried for women who were newly diagnosed with breast cancer and who had a body mass index (BMI) ≥25kg/m2. Eligible patients participated in the Moving for Life (MFL) exercise program for 16 sessions. Questionnaires were administered at baseline and at the end of the intervention. Descriptive statistics were used to summarize patient characteristics and paired t-tests were used to see if there were any significant differences before and after the intervention. Results: A total of 40 women were eligible to participate in the MFL exercise program. A total of 20 women declined to participate due to location, transportation limitations, and conflicts in schedule. Of the 18 women who enrolled in the MFL program, 13 (72%) were regular attendees and completed the study. The median age was 61 years (range: 38-76) and the average baseline BMI was 31kg/m2(range: 25-42). After completing the MFL intervention, there was a significant decrease in weight and BMI (p=0.04). The average weight loss was 10lbs. Participants also reported a greater enjoyment of exercise (p=0.02), as well as a decrease in pain related to treatment (p=0.05). Conclusions: Moving for Life is a unique exercise program for breast cancer patients and had a high rate of acceptance and completion in a cohort of overweight breast cancer patients. This study resulted in a statistically significant average weight loss of 10lbs, as well as a greater enjoyment of exercise and decrease in treatment-related pain which may impact long-term lifestyle changes. Longitudinal follow-up at 6- and 12-months will allow assessment of secondary endpoints, including exercise frequency and attitudes about exercise, allowing us to examine sustainability and changes in behaviors and attitudes over time.
Who gets treated at commission on cancer-approved programs and does it make a difference in survival?
Authors: Caggiano Vincent , Parise Carol 
Published: February 2017

114 Background: Commission on Cancer (CoC) approval has promoted improvements in cancer care in the United States. The purpose of this study is to determine if there are differences in who is treated at CoC approved versus non-approved sites and if CoC approval is associated with survival. Methods: We examined 130,655 cases of stages I-IV first primary female invasive breast cancer from the California Cancer Registry diagnosed between 2000-2010. Odds ratios (95% CI) adjusted for stage, age, grade, year of diagnosis, and ER/PR/HER2 were computed to determine if there were differences by race: white, black, Hispanic, Asian/Pacific Islander (API) and American Indian (AI); SES (low, intermediate, high) or location (urban versus rural) in the likelihood of treatment at CoC sites. Cox regression was used to assess the risk of cancer specific mortality at CoC approved versus non-approved sites. Results: CoC-approved hospitals were more likely to be urban (89%) than rural (11.2%). Race and SES were associated with being treated at CoC sites. In the lowest SES group, blacks (OR=0.82; 95% CI=0.77, 0.89) and Hispanics (OR=0.90; 95%CI=0.86, 0.95) were less likely than whites to be treated at CoC sites. Similar ORs were seen in the intermediate SES group for blacks and Hispanics. In the highest SES stratum, blacks (OR=0.67; 95%CI=0.62, 0.74), Hispanics (OR=0.76; 95%CI=0.72,0.81), and APIs (OR=0.79; 95%CI=0.75,0.83) were less likely to be treated at CoC sites. Unadjusted survival was better for CoC sites (87% vs 85%). For Stage I, only whites treated at CoC approved sites had decreased risk of mortality (HR=0.86; 95%CI=0.79, 0.95). For Stage 2, whites (HR=0.87; 95%CI=0.82, 0.93) and APIs (HR=0.71; 95%CI=0.59, 0.86) had decreased risk of mortality. Blacks (HR=0.82; 95%CI=0.70,0.99) had slightly decreased risk of mortality. For stages III and IV, no difference in risk of mortality was apparent for any race at CoC-approved sites. Conclusions: Patients treated at CoC approved sites vary by race/ethnicity and SES. While the risk of mortality is reduced for some race/ethnicities in Stages 1 and 2 when treated at CoC-approved sites, for stages III and IV patients, CoC-approval does not make a difference in risk of mortality.
Radiation exposure in patients (pts) with newly diagnosed breast cancer (BC) within first year (yr) from diagnostic procedures (DP).
Authors: Chaudhary Lubna , Knapp Sarah , Hester Samuel , Wen Sijin , Xiao Jie , Marano Gary , Kurian Sobha , Hazard Hannah , Layne Ginger , Jacobson Geraldine Meerbott , Abraham Jame 
Published: February 2017

123 Background: Radiation exposure is associated with an increased risk of secondary cancers. Few studies have examined radiation exposure from DP in BC. Methods: We retrospectively analyzed the cumulative radiation doses (millisievert [mSv]) of routine DP done in 305 pts during the 1st yr following BC diagnosis between Jan 2008-Oct 2010. Data regarding the frequency of DP including mammograms, sentinel lymph node biopsies, X-rays, computed tomographic (CT) and/or positron emission tomographic (PET) scans, MUGA scans and bone scans were collected. Mean radiation doses of DP were obtained from Departments of Nuclear Medicine and Radiation at our institution. Kruskal-Wallis test and post-hoc pairwise comparisons were used to assess the influence of various factors including age, histology, ER/PR (Estrogen/Progesterone) status and stage on the amount of radiation exposure. Results: Mean radiation exposure relative to various factors is shown in the Table. Pts < 40yrs had a significantly higher radiation dose as compared to pts > 60yrs (35.9mSv vs. 19.2mSv; p = 0.009). Pts with DCIS (ductal carcinoma in situ) had a significantly less radiation exposure as compared to IDC (infiltrating ductal carcinoma) and ILC (invasive lobular carcinoma) (8.5mSv vs. 26.7mSv and 22.4mSv respectively; p< 0.0001). Stage ≥ IIB disease was associated with a significantly higher radiation exposure (p< 0.0001). Stage ≥ IIIA was the only factor associated with a higher radiation dose from PET/CTs (p< 0.0001). Conclusions: Radiation exposure from DP is significant in the 1st yr of BC diagnosis, especially for younger and advanced stage pts. Risk is small but relevant, especially in younger pts. [Table: see text]
Impact of physician and center case volume on the adequacy of cardiac monitoring during adjuvant trastuzumab in breast cancer.
Authors: Kumachev Alexander , Chin-Yee Nicolas J. , Yan Andrew , Tomlinson George A. , Earle Craig , Trudeau Maureen E. , Ko Dennis , Krzyzanowska Monika K. , Pal Raveen , Brezden Christine B. , Gavura Scott , Lien Kelly , Chan Kelvin K. 
Published: February 2017

128 Background: A recent study suggests that cardiotoxicity from adjuvant trastuzumab (T-mab) is associated with inadequate cardiac monitoring (Ng et al. SABCS 2012). Few studies have examined the impact of centre or physician (MD) case volume (vol) on the quality of care in systemic therapy, including the adequacy of cardiac monitoring during T-mab treatment. Methods: All breast cancer patients treated with adjuvant T-mab in Ontario between 2003-2009 were identified through a provincial drug funding program. Patient demographics, hospitalizations, cardiac risk factors, cardiac imaging, comorbidities, treatment centres and MDs were ascertained. Annual case vol was calculated as the number of patients treated per year with adjuvant T-mab by each MD and centre. Cumulative case vol was calculated as the total number of patients treated with adjuvant T-mab. Centre and MD vol were divided into terciles (T1, T2 and T3) by the year of diagnosis. Inadequate cardiac monitoring was defined as per recent guidelines and per Ng et al. Hierarchical multivariable logistic regression models were constructed to examine factors associated with inadequate cardiac monitoring. Results: Our cohort consisted of 3,777 patients, 214 MDs and 68 centres. Of the total patients, 16.5% were over age 65; 30.3%, 9.4%, and 1.2% had previous diagnoses of hypertension, diabetes, and heart failure (HF), respectively; 24.3% did not receive adequate cardiac monitoring. Inadequate cardiac monitoring was associated with lower cumulative MD vol (T1: 27.9%, T2: 23.3%, T3: 20.8%, p < 0.0001) and lower annual centre vol (T1: 32.5%, T2: 19.7%, T3: 20.7%, p < 0.0001) in univariate analyses, and remained significant after adjusting for age, comorbidities, previous HF, socioeconomic status based on income, rural residence and calendar period. After adjusting for patient clustering at the MD, centre, and regional levels, lower cumulative MD vol (p=0.012), but not annual centre vol, remained a significant predictor for inadequate cardiac monitoring. Conclusions: Our findings suggest improved cardiac monitoring with greater MD experience, supporting the notion of centralization of systemic therapy to high vol MDs to optimize outcomes.
Differences between taxanes in time on therapy and associated discontinuation events in metastatic breast cancer: Results from a U.S. claims analysis.
Authors: Force Rex W. , Pugmire Brooke A. , Binder Gary , Duval Cindy , Corzo Deya , Gluck Stefan 
Published: February 2017

158 Background: Taxanes in metastatic breast cancer (mBC) have demonstrated clinical benefits but have different toxicity profiles. This study evaluated differences in time to discontinuation (D/C) between taxanes overall and by specific events associated with D/C (i.e., death, adverse events (AE), subsequent therapy). Methods: Women receiving >1 dose of either paclitaxel (P), docetaxel (D), or nab-paclitaxel (nab-P) between 2006-2009 were identified by ICD-9 codes indicative of mBC from a commercial payer claims database. Logistic regression and Cox-proportional hazards models were used to compare rates of D/C and time to D/C, respectively. Control variables were age, use of prior or concurrent chemo, and comorbidity score. Drug D/C was defined as no taxane administration for 35 days. AE within 35-days after D/C were considered taxane-associated. Death or disenrollment from the insurance plan within 90 days and initiation of subsequent therapy within 60 days after D/C were considered temporally associated with D/C. Results: 4,503 pts with mBC were included (2,599 received D; 1,643 received P, and 261 received nab-P). The most common reason for D/C in all pts was AEs (37.8%), initiation of subsequent therapy (34.4%), and death or disenrollment (8.4%). A higher proportion of pts on D (29.4%) and P (17.5%) had D/C due to neutropenia vs nab-P (6.9%, p<0.001 for both comparisons). A higher proportion of pts on nab-P (12.3%) continued on therapy until death/disenrollment vs D (8.9%, p 0.046) or P (7.1%, p 0.023). Similarly, a higher proportion of pts on nab-P (51.2%) initiated subsequent therapy at D/C of taxane vs D (31%) or P (37.3%; p<0.01 for both comparisons). Median time to D/C was 85 days for each of D and P, and 127 days for nab-P (p<0.05). Median time to D/C associated with AEs, neutropenia, death/disenrollment or subsequent therapy were significantly longer for nab-P compared with D or P (p<0.05). Conclusions: Women treated for mBC stayed on nab-P therapy 50% longer than with other taxanes. This time on therapy advantage also indicated that pts on nab-P were less likely to D/C due to AEs, more likely to stay on therapy, and more likely to be candidates for subsequent therapies.
Incidence, management, and resolution of stomatitis and noninfectious pneumonitis in BOLERO-2.
Authors: Perez Alejandra T. 
Published: February 2017

159 Background: Although the mTOR inhibitor everolimus (EVE) was generally well tolerated in combination with exemestane (EXE) in patients (pts) with HR+/HER2– advanced breast cancer, stomatitis and noninfectious pneumonitis (NIP) are the most clinically relevant and potentially dose-limiting toxicities. The incidence, grade, and clinical course of stomatitis and NIP among pts participating in the BOLERO-2 study are described. Methods: Pts were randomized 2:1 to receive EVE + EXE or placebo (PBO) + EXE. Incidence and severity of stomatitis and NIP, consequent dose interruptions/adjustments, study drug discontinuations, and time to resolution were recorded. Results: Stomatitis (any grade) occurred more frequently with EVE + EXE than with PBO + EXE (59% vs 12%, respectively). Grade 3 stomatitis occurred in 8% vs 1% of EVE + EXE vs PBO + EXE pts, respectively; no grade 4 events were reported. Onset of grade ≥ 2 stomatitis after treatment initiation was earlier for EVE + EXE arm vs PBO + EXE: median time was 15 d vs 24 d, respectively. For the EVE + EXE arm, 97% of pts with grade 3 stomatitis (n = 38) improved to ≤1 after a median of 13 d. Complete resolution was observed in 82% of pts after a median of 38 d. For the PBO + EXE arm, all pts with grade 3 stomatitis (n = 2) improved to ≤1 after a median of 18 d. Complete resolution was observed after a median of 29 d. 24% of pts on EVE + EXE required dose interruptions/adjustments vs 1% of pts on PBO + EXE, and 3% of pts (n = 13) discontinued EVE + EXE vs <1% of pts (n = 1) discontinuing PBO + EXE, all related to stomatitis. Overall, 16% in the EVE + EXE vs 0% in the PBO + EXE groups had a diagnosis consistent with NIP. For EVE + EXE, grade 1, 2, and 3 NIP occurred in 7%, 6%, and 3% of pts, respectively; no grade 4 events were reported. Complete resolution of NIP to grade ≤1 was recorded for all but 4 pts for whom NIP was still observed at last follow-up before study discontinuation. Overall, in the EVE + EXE arm, NIP was reason for dose interruption and treatment discontinuation in 7.5% and 5.6% of pts, respectively. Conclusions: In the BOLERO-2 study, stomatitis and NIP were of mild to moderate intensity and were generally reversible. Most incidents were successfully managed with palliative interventions and temporary dose modifications. Clinical trial information: NCT00863655.