Time filter

Source Type

Midtown, CO, United States

Cohn A.L.,Rocky Mountain Cancer Center | Tabernero J.,Autonomous University of Barcelona | Maurel J.,Hospital Clinic de Barcelona | Nowara E.,Center of Oncology of Poland | And 15 more authors.
Annals of Oncology | Year: 2013

Background: Targeted agents presently available for mutant KRAS metastatic colorectal cancer (mCRC) are bevacizumab and aflibercept. We evaluated the efficacy and safety of conatumumab (an agonistic monoclonal antibody against human death receptor 5) and ganitumab (a monoclonal antibody against the type 1 insulin-like growth factor receptor) combined with standard FOLFIRI chemotherapy as a second-line treatment in patients with mutant KRAS mCRC. Patients and methods: Patients with mutant KRAS metastatic adenocarcinoma of the colon or rectum refractory to fluoropyrimidine- and oxaliplatin-based chemotherapy were randomized 1: 1: 1 to receive intravenous FOLFIRI plus conatumumab 10 mg/kg (Arm A), ganitumab 12 mg/kg (Arm B), or placebo (Arm C) Q2W. The primary end point was progression-free survival (PFS). Results: In total, 155 patients were randomized. Median PFS in Arms A, B, and C was 6.5 months (HR, 0.69; P = 0.147), 4.5 months (HR, 1.01; P = 0.998), and 4.6 months, respectively; median overall survival was 12.3 months (HR, 0.89; P = 0.650), 12.4 months (HR, 1.27; P = 0.357), and 12.0 months; and objective response rate was 14%, 8%, and 2%. The most common grade ≥3 adverse events in Arms A/B/C included neutropenia (30%/25%/18%) and diarrhea (18%/2%/10%). Conclusions: Conatumumab, but not ganitumab, plus FOLFIRI was associated with a trend toward improved PFS. Both combinations had acceptable toxicity. ©The Author 2013.Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

Bendell J.C.,Sarah Cannon Research Institute | Bekaii-Saab T.S.,Ohio State University | Cohn A.L.,Rocky Mountain Cancer Center | Hurwitz H.I.,Duke University | And 8 more authors.
Oncologist | Year: 2012

Background. The Avastin® Registry: Investigation of Effectiveness and Safety (ARIES) study is a prospective, community- based observational cohort study that evaluated the effectiveness and safety of first-line treatment patterns, assessing the impact of chemotherapy choice and treatment duration. Methods. The ARIES study enrolled patients with metastatic colorectal cancer (mCRC) receiving first-line chemotherapy with bevacizumab and followed them longitudinally. The protocol did not specify treatment regimens or assessments. Analyses included all patients who initiated bevacizumab in combination with either first-line oxaliplatin with infusional 5-fluorouracil and leucovorin (FOLFOX) or irinotecan with infusional 5-fluorouracil and leucovorin (FOLFIRI). Progression-free survival (PFS) and overall survival (OS) times were estimated using Kaplan-Meier methods. Hazard ratios (HRs) were estimated with multivariate Cox regression analysis, adjusting for potential confounding factors. Results. In total, 1,550 patients with first-line mCRC were enrolled (median follow-up, 21 months) and most received FOLFOX-bevacizumab (n = 968) or FOLFIRI- bevacizumab (n = 243) as first-line therapy. The baseline characteristics and median treatment duration were generally similar between subgroups. There were no significant differences in the median PFS (10.3 months vs. 10.2 months) or OS (23.7 months vs. 25.5 months) time between the FOLFOX-bevacizumab and FOLFIRI-bevacizumab subgroups, respectively, by unadjusted analyses. Multivariate analyses showed FOLFIRI-bevacizumab resulted in a similar PFS (HR, 1.03; 95% confidence interval [CI], 0.88 -1.21) and OS (HR, 0.95; 95% CI, 0.78 -1.16) outcome as with FOLFOX-bevacizumab. The incidence proportions of bevacizumab-associated adverse events were similar for FOLFOX- and FOLFIRI-based therapies. Conclusions. In first-linemCRCpatients, the FOLFOX- bevacizumab and FOLFIRI-bevacizumab regimens were associated with similar treatment patterns and clinical outcomes. © AlphaMed Press. Source

Chen C.,Rocky Mountain Cancer Center | Dhanda R.,Rocky Mountain Cancer Center | Tseng W.-Y.,Rocky Mountain Cancer Center | Forsyth M.,Rocky Mountain Cancer Center | Patt D.A.,McKesson
Journal of Oncology Practice | Year: 2013

Purpose: Oncotype Dx 21-gene assay recurrence score (RS) predicts recurrence of early-stage breast cancer (ESBC). We investigated whether patient, tumor, or practice characteristics drive its use and explored Oncotype DX RS and chemotherapy use in subgroups. Methods: Patients with ESBC with documented estrogen receptor-positive, lymph node-negative, human epidermal growth factor receptor 2-negative tumors registered within McKesson Specialty Health's iKnowMed electronic health record were included. Patient and practice characteristics by region and size were analyzed. The association between Oncotype DX RS value and use of chemotherapy were assessed. Results: The study included 6,229 patients. Of these, 1,822 (29%) had an Oncotype DX RS result. Test use was 36%, 38%, 34%, 25%, and 6%, respectively, in patients age ≤ 45, 46-55, 56-65, 66-75, and ≥ 76 years; 33%, 25%, and 9% in patients with Eastern Cooperative Oncology Group performance status of 0, 1, and ≥ 2; 7%, 9%, 25%, 38%, 27%, and 10% in T1mic, T1a, T1b, T1c, T2, and T3 tumors; and 26%, 32%, and 33% for grades 1, 2, and 3 tumors. Of the 1,822 patients with available Oncotype DX RS, adjuvant chemotherapy use was 6%, 42%, and 84% in the low-, intermediate-, and high-risk groups. Conclusion: Patients who were younger, had better ECOG performance status, or had higher grade tumors were more likely to undergo RS testing. It appears that the RS test may have influenced the decision about whether to administer adjuvant chemotherapy: a low RS score was associated with lower chemotherapy use and a high RS score was associated with higher chemotherapy use. Copyright © 2013 by American Society of Clinical Oncology. Source

Fuchs C.S.,Dana-Farber Cancer Institute | Fakih M.,Roswell Park Cancer Institute | Schwartzberg L.,West Clinic | Cohn A.L.,Rocky Mountain Cancer Center | And 10 more authors.
Cancer | Year: 2013

BACKGROUND In patients with previously untreated metastatic colorectal cancer (mCRC), we conducted a phase 1b/randomized phase 2 trial to define the safety, tolerability, and efficacy of mFOLFOX6 plus bevacizumab (mFOLFOX6/bev) with conatumumab, an investigational, fully human monoclonal IgG1 antibody that specifically activates death receptor 5 (DR5). METHODS Twelve patients were enrolled in a phase 1b open-label dose-escalation trial of conatumumab with mFOLFOX6/bev; thereafter, 190 patients were randomized 1:1:1 to receive mFOLFOX6/bev in combination with 2 mg/kg conatumumab, 10 mg/kg conatumumab, or placebo. Therapy cycles were repeated every 2 weeks until disease progression or the occurrence of unacceptable toxicity. RESULTS In phase 1b, conatumumab with mFOLFOX6/bev was tolerated without apparent added toxicity over mFOLFOX6/bev alone. In phase 2, conatumumab with mFOLFOX6/bev did not confer a benefit in progression-free survival when compared with placebo with mFOLFOX6/bev. Toxicity was similar in all treatment arms. Following treatment, similar increases in circulating caspase-3 levels were observed in all arms. CONCLUSIONS Conatumumab with mFOLFOX6/bev did not offer improved efficacy over the same chemotherapy with placebo in first-line treatment of patients with mCRC. These data do not support further development of conatumumab in advanced CRC. Source

Grothey A.,Mayo Medical School | Flick E.D.,Genentech | Cohn A.L.,Rocky Mountain Cancer Center | Bekaii-Saab T.S.,Ohio State University | And 6 more authors.
Pharmacoepidemiology and Drug Safety | Year: 2014

Purpose: This analysis from Avastin® Registries: Investigation of Effectiveness and Safety (ARIES) examined the association between exposure to bevacizumab after disease progression (PD) and postprogression survival (PPS) in bevacizumab-exposed metastatic colorectal cancer (mCRC) through the application of time-dependent and time-fixed analytical methods. Methods: Patients with mCRC who were treated with first-line bevacizumab and who survived first PD (PD1) were included. A time-dependent Cox regression model was fitted to assess the effect of cumulative bevacizumab exposure on PPS, while controlling for potential confounders. In addition to support findings from previous studies, a modified intent-to-treat (mITT) analysis compared PPS in patients who received bevacizumab beyond disease progression (BBP) with those who did not (No-BBP). Results: Of 1550 patients, 1199 survived PD1 and had a median PPS of 13.4months. Cumulative bevacizumab exposure was associated with improved PPS (p=0.0040). After adjusting for confounders, the hazard ratios (HRs) for PPS decreased, on average, by 1.2% (range, 1.1-1.3%) with each additional dose of bevacizumab. In the mITT analysis, the median PPS for BBP (n=438) was 14.4months vs 10.6months with for No-BBP (n=667). BBP was found to be independently associated with longer PPS in a multivariable Cox regression analysis (HR, 0.84; 95% confidence interval, 0.73-0.97). Protocol-specified adverse events suspected to be associated with bevacizumab occurred in 13.0% of patients with BBP. Conclusion: This analysis supports the observation that bevacizumab exposure after PD1 is associated with longer PPS in mCRC. © 2014 John Wiley & Sons, Ltd. Source

Discover hidden collaborations