Data Submission Standards and Evidence Requirements

Presented are recommendations of the Data Submission Standards and Evidence Requirements panel from the Conference on Clinical Cancer Research along with the U.S. Food and Drug Administration's response to these recommendations

Challenges and Opportunities to Updating Prescribing Information for Longstanding Oncology Drugs.

A number of important drugs used to treat cancer-many of which serve as the backbone of modern chemotherapy regimens-have outdated prescribing information in their drug labeling. The Food and Drug Administration is undertaking a pilot project to develop a process and criteria for updating prescribing information for longstanding oncology drugs, based on the breadth of knowledge the cancer community has accumulated with the use of these drugs over time. This article highlights a number of considerations for labeling updates, including selecting priorities for updating; data sources and evidentiary criteria; as well as the risks, challenges, and opportunities for iterative review to ensure prescribing information for oncology drugs remains relevant to current clinical practice

Measuring Disease-Free Survival and Cancer Relapse Using Medicare Claims From CALGB Breast Cancer Trial Participants (Companion to 9344)

To determine the accuracy with which Medicare claims data measure disease-free survival in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We merged gold-standard clinical trial data of 45 elderly patients with node-positive breast cancer who were treated on the Cancer and Leukemia Group B (CAL-GB) adjuvant breast trial 9344 with Centers for Medicare and Medicaid Services (CMS) data files and compared the results of a CMS-based algorithm with the CALGB disease-free survival information to determine sensitivity and specificity. For 5-year disease-free survival, the sensitivity of the CMS-based algorithm was 100% (95% confidence interval [CI] = 81% to 100%), the specificity was 97% (95% CI = 83% to 100%), and the area under the receiver operator curve was 97% (95% CI = 90% to 100%). For 2-year disease-free survival, the test characteristics were less favorable: sensitivity was 83% (95% CI = 36% to 100%), specificity was 95% (95% CI = 83% to 100%), and area under the receiver operator curve was 84% (95% CI = 66% to 100%)

Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance)

PURPOSE: Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581. PATIENTS AND METHODS: C9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables. RESULTS: Fifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk. CONCLUSION: ColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis

Prevalence of hepatic iron overload and association with hepatocellular cancer in end-stage liver disease: results from the National Hemochromatosis Transplant Registry

Background : It is unclear whether mild to moderate iron overload in liver diseases other than hereditary haemochromatosis (HH) contributes to hepatocellular carcinoma. This study examined the association between hepatic iron grade and hepatocellular carcinoma in patients with end-stage liver disease of diverse aetiologies. Methods : The prevalence of hepatic iron overload and hepatocellular carcinoma was examined in 5224 patients undergoing liver transplantation. Explant pathology reports were reviewed for the underlying pathological diagnosis, presence of hepatocellular carcinoma and degree of iron staining. The distribution of categorical variables was studied using Χ 2 tests. Results : Both iron overload and hepatocellular carcinoma were the least common with biliary cirrhosis (1.8 and 2.8% respectively). Hepatocellular carcinoma was the most common in patients with hepatitis B (16.7%), followed by those with hepatitis C (15.1%) and HH (14.9%). In the overall cohort, any iron overload was significantly associated with hepatocellular carcinoma ( P =0.001), even after adjustment for the underlying aetiology of liver disease. The association between hepatic iron content and hepatocellular carcinoma was the strongest in patients with biliary cirrhosis ( P <0.001) and hepatitis C ( P <0.001). Conclusions : Iron overload is associated with hepatocellular carcinoma in patients with end-stage liver disease, suggesting a possible carcinogenic or cocarcinogenic role for iron in chronic liver disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75573/1/j.1478-3231.2007.01596.x.pd

Generalizability of Trial Results to Elderly Medicare Patients With Advanced Solid Tumors (Alliance 70802)

In the United States, patients who enroll in chemotherapy trials seldom reflect the attributes of the general population with cancer, as they are often younger, more functional, and have less comorbidity. We compared survival following three chemotherapy regimens according to the setting in which care was delivered (ie, clinical trial vs usual care) to determine the generalizability of clinical trial results to unselected elderly Medicare patients

Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial

Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown

Gemcitabine Plus Bevacizumab Compared With Gemcitabine Plus Placebo in Patients With Advanced Pancreatic Cancer: Phase III Trial of the Cancer and Leukemia Group B (CALGB 80303)

The combination of gemcitabine plus bevacizumab produced a 21% response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer. These encouraging data led Cancer and Leukemia Group B (CALGB) to conduct a double-blind, placebo-controlled, randomized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients

A Genome-Wide Association Study of Overall Survival in Pancreatic Cancer Patients Treated with Gemcitabine in CALGB 80303

CALGB 80303 was a randomized, phase III study in advanced pancreatic cancer patients treated with gemcitabine plus either bevacizumab or placebo. We prospectively collected germline DNA and conducted a genome-wide association study (GWAS) using overall survival (OS) as the endpoint