title: 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.
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.
authors.affiliation: Amgen Canada Inc, 6775 Financial Drive, Suite 100, Mississauga, ON, L5N 0A4, Canada. melaniep@amgen.com
authors.forename: Melanie
authors.initials: M
authors.lastname: Poulin-Costello
authors.forename: Laurent
authors.initials: L
authors.lastname: Azoulay
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
authors.forename: Michael
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy*; D018592:Cross-Over Studies; D018572:Disease-Free Survival; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010166:Palliative Care / Q000379:methods*; D000077544:Panitumumab; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077544:Panitumumab