TY - JOUR
T1 - An individual patient data (IPD) meta-analysis of the impact of thrombocytosis (?plts) on overall survival (OS) whilst using an intermittent chemotherapy (iCTx) strategy in advanced colorectal cancer (aCRC).
AU - Adams, Richard A
AU - Goey, Kaitlyn
AU - Chibaudel, Benoist
AU - Koopman, Miriam
AU - Punt, Cornelis J A
AU - Arnold, Dirk
AU - Hinke, Axel
AU - Hegewisch-Becker, Susanna
AU - De Gramont, Aimery
AU - Labianca, Roberto
AU - Tveit, Kjell Magne
AU - Wasan, Harpreet Singh
AU - Diaz-Rubio, Eduardo
AU - Kaplan, Richard S.
AU - Maughan, Tim
AU - Brown, Louise C.
AU - Fisher, David
PY - 2017/5/20
Y1 - 2017/5/20
N2 - Background: iCTx in pts with aCRC offers potential for improvement in QoL. The COIN trial is the largest study to compare iCTx v. continuous strategies in aCRC, a pre-specified subgroup analysis of 16 baseline factors was undertaken among pts with stable or responding disease after 3 mths of first-line therapy to see if the relative treatment effect differed by subgroup. Baseline ⇡plts alone identified a group of pts with significantly worse OS when an iCTx strategy was applied. Here we seek to validate this finding in other intermittent strategy trials. Methods: Published RCTs of iCTx in aCRC were identified via literature review. Eligible trials could allow one or more re-introductions of “full” initial regimen either upon progression or after a set period of time. Outcome and platelet data were requested and collated into a central database. The COIN trial was declared the discovery dataset and other eligible trials the validating datasets. Two co-primary hypotheses were agreed based upon the COIN trial results: Hypothesis 1: In pts with baseline ⇡plts, any planned complete stop of all therapyis detrimental to OS when compared to any maintenance strategy. Hypothesis 2: In pts with baseline ⇡plts, any planned stop of oxaliplatin(Ox) therapy is detrimental to OS when compared to any equivalent strategy where Ox is maintained. Unadjusted IPD meta-analysis was performed according to a pre-specified statistical plan. Results: All trials had broadly similar inclusion criteria . Incidence of ⇡plts range 17-32%. ⇡plts was a poor prognostic marker. Combining IPD from all trials, iCTx was not detrimental to OS. Hypothesis 1 included AIO-0207, CAIRO3, COIN B, OPTIMOX 2 and GISCAD with 1622 pts, HR for interaction of ⇡plts with treatment strategy 0.97 (0.66-1.40), p = 0.78. Hypothesis 2 included TTD MACRO, NORDIC VII and OPTIMOX I, with 1268 pts, HR for interaction 1.36 (0.71-2.62), p = 0.18. Conclusions: These IPD meta-analyses do not validate COIN trial findings that showed reduced OS in pts with baseline ⇡plts who are given a planned treatment break. Sensitivity analyses will be presented, including impact of RAS mut status.
AB - Background: iCTx in pts with aCRC offers potential for improvement in QoL. The COIN trial is the largest study to compare iCTx v. continuous strategies in aCRC, a pre-specified subgroup analysis of 16 baseline factors was undertaken among pts with stable or responding disease after 3 mths of first-line therapy to see if the relative treatment effect differed by subgroup. Baseline ⇡plts alone identified a group of pts with significantly worse OS when an iCTx strategy was applied. Here we seek to validate this finding in other intermittent strategy trials. Methods: Published RCTs of iCTx in aCRC were identified via literature review. Eligible trials could allow one or more re-introductions of “full” initial regimen either upon progression or after a set period of time. Outcome and platelet data were requested and collated into a central database. The COIN trial was declared the discovery dataset and other eligible trials the validating datasets. Two co-primary hypotheses were agreed based upon the COIN trial results: Hypothesis 1: In pts with baseline ⇡plts, any planned complete stop of all therapyis detrimental to OS when compared to any maintenance strategy. Hypothesis 2: In pts with baseline ⇡plts, any planned stop of oxaliplatin(Ox) therapy is detrimental to OS when compared to any equivalent strategy where Ox is maintained. Unadjusted IPD meta-analysis was performed according to a pre-specified statistical plan. Results: All trials had broadly similar inclusion criteria . Incidence of ⇡plts range 17-32%. ⇡plts was a poor prognostic marker. Combining IPD from all trials, iCTx was not detrimental to OS. Hypothesis 1 included AIO-0207, CAIRO3, COIN B, OPTIMOX 2 and GISCAD with 1622 pts, HR for interaction of ⇡plts with treatment strategy 0.97 (0.66-1.40), p = 0.78. Hypothesis 2 included TTD MACRO, NORDIC VII and OPTIMOX I, with 1268 pts, HR for interaction 1.36 (0.71-2.62), p = 0.18. Conclusions: These IPD meta-analyses do not validate COIN trial findings that showed reduced OS in pts with baseline ⇡plts who are given a planned treatment break. Sensitivity analyses will be presented, including impact of RAS mut status.
U2 - 10.1200/JCO.2017.35.15_suppl.e15044
DO - 10.1200/JCO.2017.35.15_suppl.e15044
M3 - Meeting Abstract
SN - 0732-183X
VL - 35
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
M1 - e15044
ER -