DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

Food and Drug Administration

Center for Drug Evaluation and Research

 

 

 

Date:	May 1, 2007
From:	Division of Biologic Oncology Products Office of Oncology Drug Products/CDER/FDA
To:	Johanna Clifford Executive Secretary, Advisors and Consultants Staff
Subject:	Errata Sheet to FDA Briefing Document for May 10, 2007 ODAC meeting

 

 

Current

"In the three years since the May 2004 ODAC meeting, the primary study data have not been submitted for any of the ongoing studies identified by Johnson & Johnson orAmgen as intended to assess these risks.”

Replaced with:

"In the three years since the May 2004 ODAC meeting, the primary study data including both raw data and the derived data which are necessary for time to event analysis of overall survival and time-to-tumor progression endpoints have not been submitted for any of the ongoing studies identified by Johnson & Johnson orAmgen as intended to assess these risks.  Raw data in an electronic dataset were submitted for EPO CAN-17 on March 28, 2007.”

"

Page 9, 2nd paragraph, 7th sentence

Current:

"The goal of this study was to demonstrate that there was no clinically important increase in the rate of thrombotic events in patients receiving ESAs compared with those receiving standard transfusion supports."

Replaced with

"The goal of this study was to demonstrate that, in patients who were not prophylactically anticoagulated, there was no clinically important increase in the rate of thrombotic events in patients receiving ESAs compared with those receiving standard transfusion supports."

 

Page 11, 3^rd paragraph, 4^th sentence

Current:

"Procrit/placebo doses were adjusted to maintain hemoglobin of 13-15 g/dL."

Replaced with:

"Procrit/placebo was held when hemoglobin reached greater than 15 g/dL and was restarted when levels returned to less than 13 g/dL. There was no dose escalation permitted if the hemoglobin increased more than 1 g/dL from baseline by week 4 of Procrit/placebo administration."

 

Page 12, 2^nd paragraph, 1^st bullet under “Additional changes to the label…”

Current:

"New dosing regimen (40,000 Ukg weekly) for the treatment of anemia associated with cancer chemotherapy (June 2004)"

Replaced with:

"New dosing regimen (500 mcg every three weeks) for the treatment of anemia associated with cancer chemotherapy (March 2006)"

 

Page 15, 1^st paragraph, 4^th sentence

Current:

"Procrit was administered at a dose of 40,000 IU/kg weekly; doses were withheld for hemoglobin > 16 g/dL."

Replaced with:

"Procrit was administered at a dose of 150 IU/kg three times per week; doses were withheld for hemoglobin > 15 g/dL."

 

Page 21, 3^rd paragraph, 4^th bullet under “Studies that are ongoing…”

Current

Studies that are ongoing with no data provided to FDA:

· EPO ANE-3010 

· 20010145

· DE20020015 (ARA 03 study)

Replaced with

Studies that are ongoing with no data provided to FDA:

· EPO ANE-3010 

· 20010145

· DE20020015 (ARA 03 study)

· FR20033005 (LNH 03B study): [note: although study still accruing, summary data from analyses assessing for early safety signals have been submitted to FDA]

 

Page 21, 4^th paragraph, 8^th bullet under “Studies that are closed; summary data only…”

Current

Studies that are closed; summary results only provided to FDA

·    EPO-CAN-17 (limited dataset containing adverse event information)

Replaced with

Studies that are closed; summary results only provided to FDA

·    EPO-CAN-17 (raw data but not derived data provided in dataset submitted on March 28, 2007)

 

Page 24, Table 9, row 2, column 7

Current

“ORR (stage 4 pts only): 37% vs. 30%

Replaced with

“ORR (stage 4 pts only): 35% vs. 30%”

 

Page 24, Table 9, row 4, column 7

Current:

“TVE (ESA vs. no ESA): 3.0% vs. 1.7%)

Replaced with:

“TVE (ESA vs. no ESA): 3.0% vs. 1.7%) ^d

 

Page 25, Table 10, row 5, column 5

Current:

" titrate to maintain Hgb 14.5-15.0"

Replaced with:

"titrate to maintain Hgb 14-15.5".

 

Page 26 Table 10, row 4, column 5

Current:

“Titrate to maintain Hgb >15 (M), >14 (F)

Replaced with

“Increase dose to 4.5 µg/kg if hgb increases < 1 g/dL at week 5.  Hold for Hgb >15 (males) or >14 (women) and resume at 50% dose reduction when Hgb ≤13.0.”

 

Page 27, 2^nd paragraph, 1^st sentence

Current:

"The 20010161 study was conducted in patients with lymphoproliferative diseases; randomization was stratified for relevant prognostic factors."

Replaced with

"The 20000161 study was conducted in patients with lymphoproliferative diseases; randomization was stratified for relevant prognostic factors."

 

Page 30, 4^th paragraph, 1st sentence

Current:

"Randomization stratified by: Hb level (<10 g/dl versus ≥10 g/dl), Geographic region (Central and East Europe versus Test of the World), RBC transfusion  history (yes versus no), tumor type/treatment categories (CLL or low grade lymphoma versus all other eligible patients), and ECOG status (0,1 versus 2)."

Replaced with

"Randomization was stratified by screening hemoglobin concentration (<10 g/dL or ≥10 g/dL), geographic region (Europe vs. Rest of World), an red blood cell transfusion given in the previous 12 weeks prior to study (yes or no), tumor type/treatment categories (have chronic lymphocytic leukemia or low grade lymphoma, receiving hormonal or antibody, all other eligible patients) and ECOG strata (0- 1, 2)."

 

Page 31, 8^th paragraph, 1st sentence

Current

"Study drug treatment: target Hgb < 15 for men and <14 for women"

Replace with

"Study drug treatment: target Hgb 13-15 for men and 13-14 for women.”

 

Page 36, 1^st paragraph, 1^st two sentences

Current:

"Study drug treatment: The target hemoglobin in the study was 13.5-16 g/dL in males and 12.5-14 g/dL in females. Eprex was given over the course of RT. The dose of Eprex was adjusted throughout the study based on the subject's hemoglobin"

Replaced with:

“Study drug treatment: The target hemoglobin in the study was 13.5-16 g/dL in males and 12.5- 1 4 g/dL in females. Procrit was given over the course of RT. The dose of Procrit was adjusted throughout the study based on the subject's hemoglobin.

 

Page 41 4^th paragraph, 3^rd sentence

Current:

"Despite study closure in March 2001, a primary efficacy and safety dataset has not been submitted to FDA as of 4/07."

Replaced with:

“Despite study closure in April 30, 2003, a primary efficacy and safety dataset has not been submitted to FDA as of 4/07.

 

Page 42, 5^th paragraph, 2^nd sentence

Current

"...; Aranesp withheld when Hgb > 15 g/dl"

Replace with

"...; Aranesp withheld when Hgb > 15.5 g/dl"

 

Page 43, 6^th paragraph, 2^nd sentence

Current:

"Despite study closure in May 2003, a primary efficacy and safety dataset has not been submitted to FDA as of April 2007."

Replace with

"The study closed in May 2003. A seven volume clinical study report and raw data were provided in an electronic dataset received on March 29, 2007. The dataset does not contain derived variables for analysis of overall survival or time to- event endpoints for tumor progression.

 

Page 44, 4^th paragraph, 2^nd bullet

Current

"Limitations to assessment of impact on tumor outcomes, OS, or TVE: Primary datasets containing information on tumor outcomes and survival not submitted"

Replace with

"Limitations to assessment of impact on tumor outcomes, OS, or TVE: Primary datasets containing raw data only. Due to lack of derived data, FDA was unable to conduct analyses on tumor outcomes and survival. FDA further notes that the analysis of OS, which includes patients with both metastatic and locally advanced disease, is not appropriate.