An analysis of the treatment effect of panitumumab on overall survival from a phase 3, randomized, controlled, multicenter trial (20020408) in patients with chemotherapy refractory metastatic colorectal cancer

Melanie Poulin-Costello, Laurent Azoulay, Eric Van Cutsem, Marc Peeters, Salvatore Siena, Michael Wolf, Melanie Poulin-Costello, Laurent Azoulay, Eric Van Cutsem, Marc Peeters, Salvatore Siena, Michael Wolf

Abstract

Panitumumab is a fully human monoclonal antibody that targets the epidermal growth factor receptor. Results from the primary analysis of a phase 3, randomized, controlled study showed a statistically significant improvement in progression-free survival for patients receiving panitumumab; however, overall survival was confounded by best supportive care (BSC) patients that crossed over to panitumumab therapy after disease progression. Three post hoc analyses are presented that approximate the panitumumab overall survival treatment effect in both the all-randomized and wild-type (WT) KRAS populations by using the BSC patients with mutant (MT) KRAS as the comparator group to discount the effect of crossover from BSC to panitumumab. The primary post hoc analysis showed a median overall survival of 6.4 months for all KRAS-evaluable patients randomized to panitumumab versus 4.4 months for patients with MT KRAS tumors randomized to BSC, yielding an adjusted hazard ratio (95 % CI) of 0.764 (0.598-0.977). Similar results were observed for the two secondary post hoc analyses. These analyses suggest a positive treatment effect of panitumumab in both the overall and WT KRAS patient populations consistent with an improvement in overall survival relative to BSC.

Trial registration: ClinicalTrials.gov NCT00113763.

Figures

Fig. 1
Fig. 1
a 20020408 Study Schema, b CONSORT diagram, c groups included in the primary post hoc analysis that compared patients with MT KRAS (n = 84) and WT KRAS (n = 124) tumors who received panitumumab versus patients with MT KRAS (n = 100) tumors who received BSC alone. d Groups included in the second post hoc analysis that compared patients with WT KRAS (n = 124) tumors who received panitumumab versus patients with MT KRAS (n = 100) tumors who received BSC alone. e Groups included in the third post hoc analysis that compared patients with WT KRAS tumors who received panitumumab (n = 124) and BSC alone (n = 119) versus patients with MT KRAS tumors who received panitumumab (n = 84) and BSC alone (n = 100)
Fig. 1
Fig. 1
a 20020408 Study Schema, b CONSORT diagram, c groups included in the primary post hoc analysis that compared patients with MT KRAS (n = 84) and WT KRAS (n = 124) tumors who received panitumumab versus patients with MT KRAS (n = 100) tumors who received BSC alone. d Groups included in the second post hoc analysis that compared patients with WT KRAS (n = 124) tumors who received panitumumab versus patients with MT KRAS (n = 100) tumors who received BSC alone. e Groups included in the third post hoc analysis that compared patients with WT KRAS tumors who received panitumumab (n = 124) and BSC alone (n = 119) versus patients with MT KRAS tumors who received panitumumab (n = 84) and BSC alone (n = 100)
Fig. 2
Fig. 2
Kaplan–Meier estimate of overall survival for KRAS-evaluable patients randomized to panitumumab versus patients randomized to BSC with KRAS mutant tumors
Fig. 3
Fig. 3
Kaplan–Meier estimate of overall survival for patients randomized to panitumumab with KRAS wild-type tumors versus patients randomized to BSC patients with KRAS mutant tumor
Fig. 4
Fig. 4
Kaplan–Meier estimate of overall survival for patients with KRAS wild-type versus KRAS mutant tumors
Fig. 5
Fig. 5
Kaplan–Meier estimate of overall survival by KRAS status among BSC patients that did not crossover to panitumumab
Fig. 6
Fig. 6
Array approach for confounding bias

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