For the treatment of wild-type KRAS metastatic colorectal cancer in previously treated patients, a head-to-head comparison of the two antibodies—cetuximab (Erbitux) and panitumumab (Vectibix)—that target the epidermal growth factor receptor (EGFR) concluded that they convey similar overall survival advantages. The results of the international phase III ASPECCT trial were presented at the 2013 European Cancer Congress by Timothy Price, MD, of the Queen Elizabeth Hospital in Adelaide, Australia.1
Prior to ASPECCT, cetuximab had prospectively demonstrated an overall survival benefit, but panitumumab had not, presumably because of heavy crossover in the pivotal panitumumab trials, Dr. Price explained.
“The crossover potentially diluted the overall survival benefit, and this has often been a discussion point regarding the two drugs,” he noted.
ASPECCT, therefore, was designed as a noninferiority trial to determine if one of these agents might be preferred over the other. The study enrolled 999 patients with KRAS wild-type metastatic colorectal cancer who had previously received irinotecan-, oxaliplatin-, and fluorouracil-based treatment (or bevacizumab [Avastin]) for metastatic disease, but no prior anti-EGFR regimens.
Patients were randomized to receive panitumumab at 6 mg/kg every 2 weeks or cetuximab at 400 mg/m2 followed by 250 mg/m2 weekly. Crossover between the arms was not allowed in the protocol, though a small and equal proportion of patients in each arm did so. For the primary endpoint, overall survival, noninferiority was determined if panitumumab preserved at least 50% of the cetuximab overall survival effect, compared with best supportive care, found in the prior NCIC CTG C0.17 trial.
Panitumumab Noninferior to Cetuximab
At a median follow-up of 9 months, panitumumab proved noninferior to cetuximab, yielding a median overall survival time of 10.4 months vs 10.0 months with cetuximab (hazard ratio [HR] = 0.97; P = .0007). The Z score of –3.19 satisfied the criteria of noninferiority (< –1.96), Dr. Price reported.
Median progression-free survival was also similar—4.1 months with panitumumab and 4.4 months with cetuximab—as were response rates: 22.0% and 19.8%, respectively.
For both agents, the safety profiles were consistent with previously reported studies. Serious adverse events were observed in 30.4% of the panitumumab arm and 33.6% of the cetuximab arm, with 13.9% and 12.1%, respectively, discontinuing the drug. Grade 3 or 4 skin toxicity (12.5% vs 9.5%) as well as hypomagnesemia (7.2% vs 2.6%) were more common with panitumumab, but infusion reactions (0.2% vs 1.8) were more common with cetuximab. There was no difference in the rate of diarrhea. ■
Disclosure: Dr. Price reported no potential conflicts of interest.
1. Price T, Peeters M, Kim TW, et al: ASPECCT: A randomized, multicenter, open-label, phase 3 study of panitumumab vs cetuximab for previously treated wild-type KRAS metastatic colorectal cancer. 2013 European Cancer Congress. Abstract LBA18. Presented September 28, 2013.
At the European Cancer Congress (ECC), Josep Tabernero, MD, PhD, Head of the Medical Oncology Department at Vall d’Hebron University in Barcelona, Spain, noted that the ASPECCT study asks a “reasonable question about the efficacy and safety of the two clinically approved anti-EGFR antibodies” and...