To: Johanna Clifford, RN, MSN
Health
Science Administrator for the Oncology Drugs Advisory Committee
Advisors and Consultants Staff
From: Ann
T. Farrell, MD
Clinical
Team Leader
Division of Oncology Drug Products
Re: Errata in FDA
Genasense Briefing Document
Date:
The following errata have
been discovered and need to be corrected in the FDA Genasense Briefing
Document.
Page 14, Paragraph 4, line 3
There is a typo. The
following sentence is incorrect:
One hundred
and should read:
One hundred
Page 18: 2^{nd}
line from the bottom
Original: … 65 cm
versus 75 cm …
Revised: … 65 mm
versus 75 mm …
Page 20, Table 6
There is a typo. In the row
labeled “Death” in the cell under the column labeled “DTIC alone” the number
should be 15 instead of 1.
Pages 31 and 33: Dotted curves in Figures 6 and 7
are not visible in the original document.
Enlarged figures are provided as below.
Figure 6: KaplanMeier Curves of Time from Randomization to 1st, 2nd, and 3rd Lesion Assessments
(Reviewer’s Figures)
[Note:
Assessments conducted after the date of documented disease progression
or death were excluded.]
Figure 1: KaplanMeier Curves of Time from Treatment Start to
1st, 2nd, and 3rd Lesion Assessment (Reviewer’s
Figures)
[Note: Assessments after documented
disease progression or death were excluded from the analysis.]
Pages 3637: Tables
1719 in the original document are to be replaced by the following three
tables. Numbers referred in the text
should be changed accordingly.
Table 17: Summary of Number of Patients with Missing
Lesion Measurements Prior to Documented Disease Progression or Death
Among Those Who Had Disease Progression or Death
(Reviewer’s Table) 


Missing at
Least One Lesion Measurement 
Missing More
Than 50% of Lesion Measurements 

Lesions 
G3139 +
DTIC [N =
263]^{†} 
DTIC [N =
260]^{†} 
G3139 +
DTIC [N =
263]^{†} 
DTIC [N =
260]^{†} 
Target 
16
(6.1%) 
13
(5.0%) 
6 (2.3%) 
2 (0.8%) 
Nontarget 
90
(34.2%) 
69
(26.5%) 
46 (17.5%) 
37 (14.2%) 
Target or nontarget 
91
(34.6%) 
69
(26.5%) 
46^{‡} (17.5%) 
37^{‡} (14.2%) 
^{†} Number of patients who had
disease progression or death in each treatment group. ^{‡ }Number
of patients who had more than 50% of missing target lesion measurements or
more than 50% of missing nontarget lesion measurements. 
Table 18:
Summary of Number of Patients with Missing Lesion Measurements First
Occurred at The Same Time of Documented Disease Progression or Death
Among Those Who Had Disease Progression or Death
(Reviewer’s Table) 


Missing at
Least One Lesion Measurement 
Missing More
Than 50% of Lesion Measurements 

Lesions 
G3139 +
DTIC [N =
263]^{†} 
DTIC [N =
260]^{†} 
G3139 +
DTIC [N =
263]^{†} 
DTIC [N =
260]^{†} 
Target 
30
(11.4%) 
25 (9.6%) 
6 (2.3%) 
6 (2.3%) 
Nontarget 
126
(47.9%) 
137
(52.7%) 
43
(16.3%) 
49
(18.8%) 
Target or nontarget 
131
(49.8%) 
145
(55.8%) 
47^{‡}
(17.9%) 
53^{‡}
(20.4%) 
^{†} Number of patients who had
disease progression or death in each treatment group. ^{‡ }Number
of patients who had more than 50% of missing target lesion measurements or
more than 50% of missing nontarget lesion measurements. 
Table 19:
Summary of Number of Patients with Missing Lesion Measurements Among
Those Who Were Censored and Had Baseline and Post Baseline Target Lesion
Measurements (Reviewer’s Table) 


Missing at
Least One Lesion Measurement 
Missing More Than 50% of Lesion Measurements 

Lesions 
G3139 +
DTIC [N = 58]^{†} 
DTIC [N = 51]^{†} 
G3139 +
DTIC [N = 58]^{†} 
DTIC [N = 51]^{†} 
Target 
7
(12.1%) 
7
(13.7%) 
3 (5.2%) 
3 (5.9%) 
Nontarget 
55
(94.8%) 
45
(88.2%) 
37
(63.8%) 
25
(49.0%) 
Target or nontarget 
55
(94.8%) 
45
(88.2%) 
37^{‡}
(63.8%) 
25^{‡}
(49.0%) 
^{†} Number of censored patients who
had baseline and post baseline lesion measurements in each treatment group. ^{‡ }Number of
patients who had more than 50% of missing target lesion measurements or more
than 50% of missing nontarget lesion measurements. 
Page 38
There is a typo. The
following sentence is incorrect:
Especially, when taking into
account missing nontarget lesion measurements (Approaches 3 and 4) there is no
statistically significant difference in progressionfree survival between
treatment groups at the significance level of 0.05.
and
should read:
Especially, when taking into
account missing nontarget lesion measurements (Approach 4) there is no
statistically significant difference in progressionfree survival between
treatment groups at the significance level of 0.05.
Page 39:
Table 21 in the original
document is to be replaced by the following table.
Table 21:
Results of Generalized Logrank Test with IntervalCensored Data
(Reviewer’s Table) 


Estimated
Median (days) 
P value
from twosided generalized logrank test 

Approach 
G3139 +
DTIC 
DTIC 

1 
22 
2 
0.016 
2 
10 
2 
0.026 
3 
10 
2 
0.031 
4 
10 
2 
0.141 
Note: Pvalue was
from generalized logrank test comparing the entire curves between the two
treatment groups. 
Page 40, Table 23
There is a typo. The pvalue
for the difference in proportions should read 0.052 not 0.52.
Page 45, Table 30
There is a typo. In the row
labeled “NonUS Median Survival Time” in the cell under the column labeled “DTIC
alone” the number should be 213 instead of 123.
Page 46, Table 33
There is a typo. In the row
labeled “Median” in the cell under the column labeled “DTIC alone” the number
should be 2008.1 instead of 2009.1.
Pages 5354:
Tables 3839 in the original
document are to be replaced by the following two tables.
Table 38:
Assessment Schedules in Simulation Studies
(Reviewer’s Table) 

Configuration 
Control Group 
Experimental Group 
1A 
Days 42, 84, 126, 168, 210, 252 
(delayed by 2 days) Days 44, 86, 128, 170, 212, 254 
1B 
Same as above 
(assessment interval 2 days longer) Days 44, 88, 132, 176, 220, 264 



2A 
Days 21, 42, 63, 84, 105, 126, 147, 168, 189, 210, 231,
252 
(delayed by 2 days) Days 23, 44, 65, 86, 107, 128, 149, 170, 191, 212, 233,
254 
2B 
Same as above 
(assessment interval 2 days longer) Days 23, 46, 69, 92, 115, 138, 161, 184, 207, 230, 253,
276 
Table
39: Simulation Results under Equal
ProgressionFree Survival Distributions (Reviewer’s Table) ( 

Configuration 
Sample
size per treatment group 
Median (days) 
Probability of false inference^{†} 
Logrank
Pvalue^{‡} 

G3139 + DTIC 
DTIC 

1A 
100 
86 
84 
0.66 
0.094 

300 
86 
84 
0.98 
0.004 
1B 
100 
88 
84 
0.60 
0.114 

300 
88 
84 
0.97 
0.007 
2A 
100 
65 
63 
0.18 
0.358 

300 
65 
63 
0.41 
0.198 
2B 
100 
69 
63 
0.10 
0.427 

300 
69 
63 
0.21 
0.330 
^{†} The probability of false
inference was estimated by the proportion of the 5000 replications where the
null hypothesis was rejected. This
represented the probability of falsely inferring a difference in
progressionfree survival between the two treatment groups. ^{‡} This was the average of 5000
pvalues. Each simulation produced a
pvalue. These pvalues were from
twosided logrank test comparing progressionfree survival between treatment
groups. 