ASPECCT: A Randomised, Multicentre, Open-Label, Phase 3 Study of Panitumumab Vs Cetuximab for Previously-Treated Wild-Type (WT) KRAS Metastatic Colorectal Cancer (mCRC) (#44)
Background: Epidermal growth factor receptor (EGFR)-targeting monoclonal antibodies have demonstrated efficacy for the treatment of WT KRAS mCRC. ASPECCT is a non-inferiority trial comparing the efficacy and safety of panitumumab with cetuximab in chemorefractory WT KRAS mCRC.
Methods: Adult patients (ECOG PS 0-2, prior irinotecan, oxaliplatin and fluorouracil-based treatment for mCRC and no prior anti-EGFR treatment) were stratified by geographic region and ECOG PS and randomised 1:1 to receive panitumumab 6mg/kg q2w or cetuximab (400mg/m2 then 250mg/m2 qw) until disease progression (PD), intolerability, consent withdrawal or death. Treatment crossover was not allowed. The primary endpoint was overall survival (OS). Non-inferiority was concluded if panitumumab preserved at least 50% of the cetuximab OS effect versus best supportive care using a synthesis method. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Global enrolment has been completed.
Results: 999 patients were randomised and treated: 499 panitumumab, 500 cetuximab. Demographics were balanced between arms. Non-inferiority of OS with panitumumab versus cetuximab was met. Median OS in the panitumumab and cetuximab arms was 10.4 and 10.0 months, respectively, hazard ratio (HR) (95% CI) (panitumumab:cetuximab): 0.97 (0.84–1.11); p=0.0007. OS retention rate (95% CI) was 1.06 (0.82–1.3). Median PFS was 4.1 and 4.4 months, respectively, HR (95% CI): 1.00 (0.88–1.14). ORRs were 22% and 19.8%, respectively. Worst grade 3, 4, and 5 adverse events (AEs) for panitumumab/cetuximab, respectively, were 36.3%/31.6%, 7.5%/5.4%, and 5.8%/9.9% (69% of all grade 5 AEs related to PD). Grade 3 and 4 (panitumumab/cetuximab, respectively) AEs of interest were skin toxicity 12.5%/9.5%, hypomagnesaemia 7.3%/2.6% and infusion reactions 0.2%/1.8%.
Conclusions: The phase 3 ASPECCT study met the primary endpoint of non-inferiority of OS of panitumumab versus cetuximab in chemorefractory WT KRAS mCRC. Observed safety profiles between the treatment arms were consistent with previously-reported studies for both agents.