Amgen has reported detailed results from the phase III ASPECCT ('763) trial comparing Vectibix (panitumumab) to Erbitux (cetuximab) for the treatment of wild-type KRAS metastatic colorectal cancer in patients who have not responded to chemotherapy. The study met its primary endpoint, demonstrating that panitumumab was non-inferior to cetuximab for overall survival.

These results were presented at the 17th ECCO - 38th ESMO - 32nd ESTRO European Cancer Congress in Amsterdam.

The prospective study showed that the median overall survival for patients treated with panitumumab was 10.4 months (range 9.4 months to 11.6 months) compared to 10 months (range 9.3 months to 11.0 months) for patients treated with cetuximab (95 percent CI, 0.84-1.11, p=0.0007).

"ASPECCT was a well-conducted and robust phase III trial involving nearly 1,000 patients globally with metastatic colorectal cancer," said Sean E Harper, MD, executive vice president of Research and Development at Amgen. "Colorectal cancer is a devastating disease and these results provide physicians with important new information about the role Vectibix can play as they evaluate treatment options."

In the study, progression-free survival was a median of 4.1 months in patients treated with panitumumab versus 4.4 months in patients treated with cetuximab (HR=1.00, 95 per cent CI, 0.88, 1.14). Objective response rate, which is the percentage of patients who experienced tumour size reduction, was 22 per cent for patients treated with panitumumab compared to 19.8 per cent for patients in the cetuximab arm (Odds Ratio 1.15, 95 per cent CI, 0.83, 1.58).

In the safety analysis, the profiles of both treatments were consistent with previously reported studies. Adverse events (AEs) included known events such as rash, low levels of magnesium in the blood and infusion reactions.

In Europe, the ASPECCT trial is a Specific Obligation for Vectibix as part of the European Medicine Agency's (EMA) conditional marketing authorization.

ASPECCT is a global, randomized, multi-centre, open-label, phase III non-inferiority trial designed to compare the effect of panitumumab versus cetuximab on overall survival for monotherapy treatment of chemorefractory metastatic colorectal cancer (mCRC) in 999 patients with wild-type KRAS tumors (primary endpoint). Secondary endpoints included safety, patient reported outcomes, progression-free survival, time to response, time to treatment failure and duration of response.

Patients were randomized in a 1:1 ratio to receive 6 mg/kg of intravenous panitumumab every 14 days or 400 mg/m2 of an initial dose of intravenous cetuximab, followed by 250 mg/m2 of intravenous cetuximab every seven days.

Results from studies performed over the last 30 years indicate that KRAS plays an important role in cell growth regulation. In mCRC, EGFR transmits signals through a set of intracellular proteins. Upon reaching the nucleus, these signals instruct the cancer cell to reproduce and metastasize, leading to cancer progression. Anti-EGFR antibody therapies work by inhibiting the activation of EGFR, thereby inhibiting downstream events that lead to malignant signaling. However, in patients whose tumors harbor a mutated KRAS gene, the KRAS protein is always turned "on," regardless of whether the EGFR has been activated or therapeutically inhibited. Common KRAS mutations occurring in exon 2 (codons 12/13) are present in approximately 40 to 50 per cent of mCRC patients.

Vectibix is the first fully human anti-EGFR antibody approved by the United States Food and Drug Administration (FDA) for the treatment of mCRC. Vectibix was approved in the US as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.

The effectiveness of Vectibix as a single agent for the treatment of EGFR-expressing mCRC is based on progression-free survival. Currently no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Vectibix.

Retrospective subset analyses of mCRC trials have not shown a treatment benefit for Vectibix in patients whose tumours had RAS mutations. In the EU, the use of Vectibix is not recommended for the treatment of colorectal cancer with these mutations.

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