Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer
2004 · paper · Clinical trials
A randomized trial in 813 patients with previously untreated metastatic colorectal cancer, adding bevacizumab or placebo to irinotecan, fluorouracil and leucovorin. Bevacizumab extended median survival from 15.6 to 20.3 months, with more grade 3 hypertension.
1 finding
Reference or label Table 4 headers 'IFL plus Placebo (N=397)' and 'IFL plus Bevacizumab (N=393)': several printed percentages (e.g. 84.9, 44.9, 11.0, 37.0, 32.4, 2.6 for N=393; 74.0, 39.6, 31.1, 16.2, 5.1 for N=397) cannot be obtained from any whole-number count over these denominators.
- p. 6 Table 4 column headers
(N=397)
- p. 6 Table 4 column headers
(N=393)
- p. 6 Table 4, Any grade 3 or 4 adverse event
84.9†
- p. 6 Table 4, Hypertension Grade 3
11.0†
Only the authors can say what is right here.
Judge's note: Checked on the page 6 image and recomputed. With N=393, 333 and 334 patients give 84.73% and 84.99%, so no count gives 84.9; 43 and 44 give 10.94% and 11.20%, so none gives 11.0. With N=397, 293 and 294 give 73.80% and 74.06%, so none gives 74.0; 123 and 124 give 30.98% and 31.23%, so none gives 31.1. Denominators of 396 and 392 reproduce these values. The table footnote describes a single safety population, so row-specific denominators are not stated anywhere. The authors would need to confirm whether the Ns or the percentages are right.
Second check: another model agreed
Report a problem with this finding
5 minor (typos and the like; most checked by the judge only)
Wording Discussion: 'the addition of bevacizumab to IFL or to fluorouracil alone6,19'. Both cited studies (ref 6: 'bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone'; ref 19: '5-FU/LV/BV') used fluorouracil plus leucovorin.
- p. 7 Discussion, right column
tion of bevacizumab to IFL or to fluorouracil alone
- p. 2 Introduction
the addition of bevacizumab to fluoro-uracil plus leucovorin
- p. 7 Discussion, right column, paragraph on oxaliplatin
tion of bevacizumab to IFL or to fluorouracil alone6,19
- p. 8 References 6 and 19
bevacizumab plus fluorouracil (FU)/leu-covorin (LV) with FU/LV alone
Judge's note: Checked on the images of pages 7 and 2, and against reference entries 6 and 19 in the text. The introduction and Table 1 also describe the regimen as fluorouracil plus leucovorin, so the Discussion drops leucovorin. 'Alone' probably means 'without irinotecan', so this is a wording slip.
Second check: another model agreed
Report a problem with this finding
Wording Assessments defines NCI CTC grade 3 as "a grade of 3 serious adverse events". Grade 3 means severe, and the same paragraph lists "all serious adverse events" as a separate safety measure.
- p. 3 Assessments, left column
a grade of 3 serious ad-verse events
Judge's note: Checked on the page 3 image. The wording is printed as quoted. In the same paragraph, 'serious adverse events' is used as a distinct prespecified category, so calling grade 3 'serious' runs two concepts together. This is a wording issue only; no data are affected.
Second check: another model agreed
Report a problem with this finding
Wording Table 3 labels the duration-of-response hazard ratio 0.62 'Hazard ratio for relapse', while the abstract and the Efficacy text call it 'hazard ratio for progression, 0.62; P=0.001'.
- p. 4 Table 3, last row
Hazard ratio for relapse
- p. 5 Efficacy paragraph
hazard ratio for progression, 0.62; P=0.001
Judge's note: Checked on the images of pages 4 and 5. Both labels are printed as described and refer to the same 0.62 value. For responders, relapse and progression mean the same event, so this is a terminology inconsistency rather than a data error.
Second check: another model agreed
Report a problem with this finding
Wording Table 2 shows ECOG performance status 2 in '<1' percent of each group, but the eligibility criteria require 'an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1'.
- p. 4
* There were no significant differences between groups. IFL denotes irinotecan,
Only the authors can say what is right here.
Judge's note: Checked Table 2 on the page 4 image and the eligibility text on page 2. The randomization strata are also only 0 vs 1. The paper gives no explanation for the status-2 patients (for example a protocol deviation or a change in status between screening and baseline). The numbers are very small, so only the authors can clarify.
Second check: another model agreed
Report a problem with this finding
Typo The monitoring body has three names: 'data-monitoring committee' (study design and statistical analysis), 'data-safety monitoring committee' (page 3) and 'Data and Safety Monitoring Board' (acknowledgments, page 7).
- p. 3 Assessments
data-safety monitoring committee
- p. 7 Acknowledgments
Data and Safety Monitoring Board
Judge's note: Checked on the images of pages 3, 4 and 7, and by searching the text. The paper never says these are different bodies, so this is most likely inconsistent naming of one committee. Either name could be correct.
Second check: none (judge only)