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An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204).

ABSTRACT: OBJECTIVES:Evaluate toxicity of two treatment arms, A (cetuximab) and B (bevacizumab), when combined with gemcitabine, and chemoradiation in patients with completely resected pancreatic carcinoma. Secondary objectives included overall survival (OS) and disease-free survival (DFS). METHODS:Patients with R0/R1 resection were randomized 1:1 to cetuximab or bevacizumab administered in combination with gemcitabine for two treatment cycles. Next three cycles included concurrent cetuximab/bevacizumab plus chemoradiation, followed by one cycle of cetuximab/bevacizumab. Cycles 7-12 included cetuximab/bevacizumab with gemcitabine. Cycles were 2 weeks. Frequency of specific toxicities was summarized for each treatment arm at two times during the study, after chemotherapy but prior to chemoradiation and after all therapy. RESULTS:A total of 127 patients were randomized (A, n = 65; B, n = 62). Prior to chemoradiation, the overall rate for toxicities of interest was 10% for arm A and 2% for arm B. After all therapy, the overall rates for toxicities of interest were 30 and 25% for arms A and B, respectively. Overall median OS and DFS were 17 and 11 months, respectively, which is not a significant improvement over expected survival rates for historical controls. CONCLUSIONS:Both treatments were tolerable with manageable toxicities, and were safe enough for a phase III trial had this been indicated.

SUBMITTER: Berlin JD

PROVIDER: S-EPMC5828967 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204).

Berlin Jordan D JD Feng Yang Y Catalano Paul P Abbruzzese James L JL Philip Philip A PA McWilliams Robert R RR Lowy Andrew M AM Benson Al B AB Blackstock A William AW

Oncology 20171018 1

<h4>Objectives</h4>Evaluate toxicity of two treatment arms, A (cetuximab) and B (bevacizumab), when combined with gemcitabine, and chemoradiation in patients with completely resected pancreatic carcinoma. Secondary objectives included overall survival (OS) and disease-free survival (DFS).<h4>Methods</h4>Patients with R0/R1 resection were randomized 1:1 to cetuximab or bevacizumab administered in combination with gemcitabine for two treatment cycles. Next three cycles included concurrent cetuxima ...[more]

PMID: 29040974

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Project description:BACKGROUND:The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum. SUBJECTS, MATERIALS, AND METHODS:Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2?weeks for 12 cycles. RESULTS:E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ??3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p = .029).The most common grade 3-4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue. CONCLUSION:At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer. IMPLICATIONS FOR PRACTICE:At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed.

Project description:IntroductionECOG-ACRIN E1505 was a phase 3 randomized trial of adjuvant chemotherapy with or without bevacizumab for patients with stages IB (>4 cm) to IIIA NSCLC. We sought to estimate the incidence and risk factors for brain recurrence as compared with extracranial recurrences (ECRs).MethodsECOG-ACRIN E1505 noted that bevacizumab failed to improve overall survival (OS) (OS hazard ratio [HR] = 0.99 [0·82-1·19], p = 0.90) or recurrence-free survival when added to chemotherapy in the adjuvant setting. The cumulative incidence of brain/ECR was estimated after adjusting for recurrence at other sites and death as competing events. A multivariable regression model was fitted using competing risk analysis to evaluate the effect of covariates on brain recurrence incidence.ResultsMedian follow-up was 50.4 months. Among the 1501 patients enrolled, 472 developed ECR. There were 122 patients who had recurrence in the brain with or without simultaneous ECR as the first recurrence site (all-brain recurrences [ABRs]), and 84 of those with ABRs had recurrence in the brain only (isolated-brain recurrence [IBR]). The incidence of ABR, IBR, and ECR at 6 years was 9.9%, 5.9%, and 38.8%, respectively. Chemotherapy plus bevacizumab was associated with a decreased incidence of ABR (HR = 0.64, p = 0.02) and IBR (HR = 0.62, p = 0.032), but there was no significant trend for an OS decrement in the bevacizumab arm versus the control arm for both ABR and IBR. Median survivals associated with IBR, ABR, and ECR were 9.5, 9.5, and 14.1 months, respectively. Nonsquamous histology (HR = 1.87, p = 0.003) was also associated with ABR. ECR was associated with nonsquamous NSCLC histology (HR = 1.79, p < 0.01) and stage/N2 involvement (HR = 1.13/1.37, both p < 0.01).ConclusionsThe addition of bevacizumab to chemotherapy was associated with reduction in brain recurrences, but not ECR. Brain metastases whether isolated or not are associated with a lower median survival than ECR and unlike ECR are not associated with traditional staging variables.

Project description:BackgroundUncertainty regarding the reproducibility of the apparent diffusion coefficient (ADC) hampers the use of quantitative diffusion-weighted imaging (DWI) in evaluation of the prostate with magnetic resonance imaging MRI. The quantitative imaging biomarkers alliance (QIBA) profile for quantitative DWI claims a within-subject coefficient of variation (wCV) for prostate lesion ADC of 0.17. Improved understanding of ADC reproducibility would aid the use of quantitative diffusion in prostate MRI evaluation.PurposeEvaluation of the repeatability (same-day) and reproducibility (multi-day) of whole-prostate and focal-lesion ADC assessment in a multi-site setting.Study typeProspective multi-institutional.SubjectsTwenty-nine males, ages 53 to 80 (median 63) years, following diagnosis of prostate cancer, 10 with focal lesions.Field strength/sequence3T, single-shot spin-echo diffusion-weighted echo-planar sequence with four b-values.AssessmentSites qualified for the study using an ice-water phantom with known ADC. Readers performed DWI analyses at visit 1 ("V1") and visit 2 ("V2," 2-14 days after V1), where V2 comprised scans before ("V2pre") and after ("V2post") a "coffee-break" interval with subject removal and repositioning. A single reader segmented the whole prostate. Two readers separately placed region-of-interests for focal lesions.Statistical testsReproducibility and repeatability coefficients for whole prostate and focal lesions derived from median pixel ADC. We estimated the wCV and 95% confidence interval using a variance stabilizing transformation and assessed interreader reliability of focal lesion ADC using the intraclass correlation coefficient (ICC).ResultsThe ADC biases from b0 -b600 and b0 -b800 phantom scans averaged 1.32% and 1.44%, respectively; mean b-value dependence was 0.188%. Repeatability and reproducibility of whole prostate median pixel ADC both yielded wCVs of 0.033 (N = 29). In 10 subjects with an evaluable focal lesion, the individual reader wCVs were 0.148 and 0.074 (repeatability) and 0.137 and 0.078 (reproducibility). All time points demonstrated good to excellent interreader reliability for focal lesion ADC (ICCV1 = 0.89; ICCV2pre = 0.76; ICCV2post = 0.94).Data conclusionThis study met the QIBA claim for prostate ADC. Test-retest repeatability and multi-day reproducibility were largely equivalent. Interreader reliability for focal lesion ADC was high across time points.Level of evidence1 TECHNICAL EFFICACY: Stage 2 TOC CATEGORY: Pelvis.

Dataset Information

An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204).

Publications

An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204).

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