Amgen announces PRIME '203' and '181' Phase 3 trial results

Amgen (Nasdaq: AMGN) today announced that results from the PRIME '203' and '181' pivotal Phase 3 trials evaluating Vectibix® (panitumumab) in combination with chemotherapy (FOLFOX or FOLFIRI) as a first and second-line treatment for metastatic colorectal cancer (mCRC), respectively, were published online in the Journal of Clinical Oncology.

"Both studies demonstrated that Vectibix administered with chemotherapy significantly improved progression-free survival in patients with wild-type KRAS mCRC," said Marc Peeters, M.D., Ph.D., Professor of Oncology, Antwerp University Hospital and '181' trial lead investigator and study author. "The adverse event profiles in both trials were as expected for an anti-EGFR antibody treatment used in combination with these types of chemotherapy regimens. Additionally, these data reinforce that KRAS status should be known when choosing treatment strategies."

PRIME '203' Results in First-Line mCRC Demonstrate Vectibix Combined with Chemotherapy (FOLFOX) Helped Patients with Wild-type KRAS mCRC Live Longer Without their Disease Worsening (Progression-Free Survival or PFS)

• The addition of Vectibix to FOLFOX (an oxaliplatin-based chemotherapy) significantly improved PFS (median 9.6 months for Vectibix plus FOLFOX versus 8.0 months for patients treated with FOLFOX alone, hazard ratio 0.80; 95 percent CI: 0.66-0.97;>KRAS mCRC.  
• Although numerically greater (23.9 months versus 19.7 months, hazard ratio 0.83; 95 percent CI: 0.67-1.02), the improvement in overall survival (OS) (secondary endpoint) in the Vectibix arm did not achieve statistical significance>
• Importantly, in patients with tumors harboring activating KRAS mutations, PFS was significantly inferior in the Vectibix arm. For patients with mutant KRAS tumors, median PFS was 7.3 months with Vectibix in combination with FOLFOX versus 8.8 months with FOLFOX alone (hazard ratio 1.29; 95 percent CI: 1.04-1.62;>
• These data confirm previous findings when oxaliplatin-based chemotherapy and an anti-EGFR antibody were combined in patients bearing tumors with activating KRAS mutations.
• The response rate of Vectibix plus chemotherapy was higher than chemotherapy alone in the wild-type KRAS patient population as measured by blinded central review (55 percent versus 48 percent in the FOLFOX only arm).
• Tumor KRAS status was ascertained in 93 percent of the 1,183 patients enrolled in the PRIME '203' trial, the highest number ever prospectively reported for a first-line trial.

"The outcome of this high quality trial demonstrated that Vectibix, which was administered every two weeks, improved progression-free survival as a first-line metastatic colorectal cancer treatment in a selected patient population," said Jean Yves-Douillard, M.D., Ph.D., director Clinical and Translational Research, Medical Oncology Branch, Centre R Gauducheau, France and PRIME '203' trial lead investigator and study author.

'181' Results in Second-Line mCRC Demonstrate Vectibix Combined with Chemotherapy (FOLFIRI) Helped Patients with Wild-type KRAS mCRC Live Longer Without their Disease Worsening (PFS)

• Results of the '181' trial showed that the addition of Vectibix to FOLFIRI (an irinotecan-based chemotherapy) significantly improved PFS (co-primary endpoint) (median 5.9 months for Vectibix plus FOLFIRI versus 3.9 months for patients treated with FOLFIRI alone, hazard ratio 0.73; 95 percent CI: 0.59-0.90;>KRAS mCRC.
• Although numerically greater (median 14.5 months versus 12.5 months; hazard ratio 0.85; 95 percent CI: 0.70-1.04), the improvement in overall survival (co-primary endpoint) in the Vectibix arm did not achieve statistical significance>
• The addition of Vectibix to chemotherapy in the '181' trial resulted in greater than a three-fold improvement (35 percent versus 10 percent) in response rate in the wild-type KRAS patient population, as measured by a blinded central review.
• Tumor KRAS status was ascertained in 91 percent of the 1,186 patients enrolled in the '181' trial, the highest number ever prospectively reported for a second-line trial.
• In this study, the addition of Vectibix had no positive or negative effect on PFS or OS in patients with tumors harboring activating KRAS mutations.

"The response rate seen in the '181' trial is among the highest ever reported in the second-line metastatic colorectal cancer setting," said Emily Chan, M.D., Ph.D., Assistant Professor of Medicine, Vanderbilt-Ingram Cancer Center and '181' study investigator and author. "Additionally, the tissue acquisition from both the '181' and '203' studies has yielded a large repository of informative data regarding the KRAS biomarker, and holds the potential of providing even more information in the future."

In general, adverse events rates were comparable across arms in both studies, with the exception of known toxicities associated with anti-EGFR therapy, such as rash, diarrhea, and hypomagnesemia. Vectibix-related grade 3/4 infusion reactions were reported in less than one percent of patients.

Originally designed to compare the treatment effect in the overall mCRC patient population, both studies were amended to analyze outcomes with respect to the presence or absence of activating mutations in KRAS in the tumor itself. These are the first Phase 3 studies to prospectively analyze the effect of an EGFR inhibitor based on KRAS status in patients with previously treated mCRC.

Results from both trials were previously presented at Europe's largest cancer conference, ECCO 15 – ESMO 34, in September 2009, at the 2010 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in January, and at the 2010 American Society of Clinical Oncology (ASCO) Annual Meeting in June.