Panitumumab proved noninferior to cetuximab in extending overall survival in patients with chemorefractory KRAS wild-type metastatic colorectal cancer.
Timothy Price, MD
Panitumumab (Vectibix) proved noninferior to cetuximab (Erbitux) in extending overall survival (OS) in patients with chemorefractory KRAS wild-type metastatic colorectal cancer (mCRC), according to the results of the international ASPECCT trial.
ASPECCT is the first head-to-head, randomized phase III study evaluating the two EGFR-targeted monoclonal antibodies in patients with mCRC. The results were presented at the 2013 European Cancer Congress by Timothy Price, MD, of the Queen Elizabeth Hospital in Adelaide, Australia.
At the time that ASPECCT was initiated, cetuximab had prospectively demonstrated an OS benefit, while single-agent panitumumab had not. Price explained that, in a pivotal trial, the lack of OS benefit with panitumumab may have been due to a 70% cross-over rate from the control arm to the panitumumab arm.
“The crossover potentially diluted the overall survival benefit, and this has often been a discussion point between the two drugs,” he noted.
ASPECCT, therefore, was designed as a noninferiority trial to determine if the two anti-EGFR agents provide a comparable survival benefit. The study enrolled 999 KRAS wild-type mCRC patients who had previously received irinotecan-, oxaliplatin-, and fluorouracil-based treatment for metastatic disease, but no prior anti-EGFR regimens; about 25% of patietns had received prior bevacizumab.
Patients were randomized 1:1 to receive panitumumab (6 mg/kg every 2 weeks) or cetuximab (400 mg/m2 followed by 250 mg/m2 weekly). Although crossover between the arms was not allowed, a small proportion of patients did cross over, but it was well balanced between the arms.
The primary endpoint was OS. Noninferiority was determined if panitumumab preserved at least 50% of the cetuximab OS effect compared with best supportive care, as found in the NCIC CTG C0.17 trial.
At a median follow-up of >9 months, panitumumab proved noninferior to cetuximab. Median OS was 10.4 months with panitumumab and 10.0 months with cetuximab (hazard ratio [HR] = 0.97; 95% CI, 0.84-1.11; P = .0007). The Z score was -3.19, satisfying the criteria of noninferiority (< -1.96), Price reported.
“It is quite evident that the primary outcome—the overall survival curves—essentially mirror each other, with no obvious differences,” Price noted.
Median progression-free survival was also similar: 4.1 months with panitumumab and 4.4 months with cetuximab (HR = 1.00; 95% CI, 0.88-1.14). The objective response rates were 22.0% and 19.8%, respectively.
The safety profiles between the two arms were consistent with previously reported studies for both agents. 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. Skin toxicity grade 3 or 4 was more common with panitumumab (12.5% vs. 9.5%), as was hypomagnesemia (7.2% vs. 2.6%), but infusion reactions were more common with cetuximab (1.8% vs 0.2%).
“No new toxicities or safety signals were identified for panitumumab,” Price said.
Josep Tabernero, MD, PhD
Josep Tabernero, MD, PhD, Head of Gastrointestinal Tumors at Vall d’Hebron University in Barcelona, Spain, formally discussed the ASPECCT trial. He said the study was designed to answer a “reasonable question,” ie, whether panitumumab was as active as cetuximab, which had previously shown an OS advantage.
“This large study provides a very provocative amount of information…and showed that the results are completely equal in terms of response rate, progression-free survival, and overall survival in the chemorefractory setting.”
Tabernero added that the results cannot be applied to other treatment settings or other tumors.
Price T, Peeters M, Kim TW, et al. ASPECCT: a randomized, multicenter, open-label, phase 3 study of panitumumab (pmab) vs cetuximab (cmab) for previously treated wild-type (WT) KRAS metastatic colorectal cancer (mCRC). Presented at: European Cancer Congress 2013; September 27-October 1, 2013; Amsterdam, The Netherlands. Abstract LBA18.