Panitumumab (Vectibix) proved noninferior to cetuximab (Erbitux) in overall survival (OS) in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC), according to the results of ASPECT (A Study of Panitumumab Efficacy and Safety Compared to Cetuximab). ASPECT is the first head-to-head, open-label, randomized, multicenter, international, phase 3 study designed to determine if the 2 epidermal growth factor receptor (EGFR)-targeted monoclonal antibodies provide a comparable survival benefit in patients with mCRC (Price TJ, et al. Lancet Oncol. 2014;15:569-579).
From February 2010 to July 2012, researchers enrolled patients aged ?18 years with chemotherapy-refractory mCRC, an Eastern Cooperative Oncology Group performance status of ?2, and wild-type KRAS exon 2 status. Of the 1010 patients enrolled, 999 began study treatment. Patients were randomized 1:1 to receive panitumumab (N = 499; 6 mg/kg intravenously once every 2 weeks) or cetuximab (N = 500; 400 mg/m2 intravenously followed by 250 mg/m2 weekly).
The primary end point was OS. Noninferiority was determined if panitumumab preserved ?50% of the cetuximab OS effect compared with best supportive care. The median duration of treatments was 14.3 weeks for panitumumab and 14.1 weeks for cetuximab.
At a median follow-up of >9 months, the findings showed that panitumumab was noninferior to cetuximab. The median OS was 10.4 months with panitumumab and 10 months with cetuximab (hazard ratio [HR], 0.97, 95% confidence interval [CI], 0.84-1.11; P = .007). The Z score was ?3.19, meeting the criteria of noninferiority of less than ?1.96. Median progression-free survival was also similar between panitumumab and cetuximab (4.1 months and 4.4 months, respectively; HR, 1; 95% CI, 0.88-1.14).
The incidence of adverse events of any grade was consistent across treatment groups. Serious adverse events were reported in 30% of the panitumumab group and 34% of the cetuximab group, with 35% and 36%, respectively, needing dose reductions because of adverse events. Grade 3 or 4 skin toxicity was more common with panitumumab than with cetuximab (13% vs 10%, respectively), as was hypomagnesemia (7% vs 3%, respectively). However, infusion reactions were more common with cetuximab than with panitumumab (2% vs <0.5%, respectively).
Considering the consistency of efficacy and toxicity that was observed, small but meaningful differences in the rate of grade 3 or 4 infusion reactions and the differences in dose scheduling can guide clinician choice of anti-EGFR therapy for this patient population, concluded the researchers.
