Amgen today announced that the Phase 3 PRIME "203" trial evaluating Vectibix(panitumumab) administered in combination with FOLFOX (an oxaliplatin-basedchemotherapy) as a first-line treatment of metastatic colorectal cancer (mCRC)failed to meet a secondary endpoint of overall survival. Earlier this year,it was announced that the trial met its primary endpoint by significantlyprolonging progression-free survival (PFS) in the first-line treatment ofpatients with KRAS wild-type mCRC.
The prospective analysis of the 203 study showed that Vectibix, when addedto a FOLFOX chemotherapy regimen in patients with KRAS wild-type mCRC,resulted in a median overall survival of 23.9 months compared to 19.7 monthsfor patients treated with FOLFOX alone. The median overall survival differenceof 4.2 months in the Vectibix arm did not reach statistical significance.
"As we previously announced, the 203 study met its primary endpoint ofprogression-free survival in the first-line treatment of patients with KRASwild-type metastatic colorectal cancer," said Roger M. Perlmutter, M.D.,Ph.D., executive vice president of Research and Development at Amgen. "Whilenot statistically significant, we are also encouraged by the positive trend ofthe data for overall survival for these patients treated with Vectibix."Overall survival appeared to be reduced in patients with KRAS mutanttumors receiving Vectibix. Although not statistically significant, thisresult emphasizes the importance, as described in product labeling, ofensuring that patients receiving Vectibix do not bear tumors containing KRASmutations.
Overall, the adverse event profile was as anticipated for an anti-EGFRantibody in combination with oxaliplatin-based chemotherapy, including knownevents such as rash, diarrhea and hypomagnesemia. Vectibix-related grade 3infusion reactions were reported for two patients (less than 1 percent).Originally designed to compare the treatment effect in the overallpopulation, the study was amended to analyze outcomes with respect to thepresence or absence of activating mutations in KRAS in the tumor itself. TumorKRAS status was ascertained in more than 90 percent of the 1,183 patientsenrolled in the trial.
Available results from the trial were presented earlier this year at the2009 ECCO 15 - ESMO 34 European Multidisciplinary Congress in Berlin, Germanyshowing that Vectibix significantly improved median progression-free survivalby 1.6 months (9.6 versus 8.0 months for patients treated with FOLFOX alone,in patients with KRAS wild-type mCRC (primary endpoint). Further, the additionof Vectibix to chemotherapy also improved response rate in the KRAS wild-typepatient population as measured by blinded central review (55 percent versus 48percent in the FOLFOX only arm).
The data for the 203 study has been submitted for consideration ofpresentation at the American Society of Clinical Oncology - TheGastrointestinal Cancers Symposium Meeting for 2010.Study Design
Patients enrolled in the "203" or PRIME trial (Panitumumab Randomizedtrial in combination with chemotherapy for Metastatic colorectal cancer todetermine Efficacy) were randomized to receive either 6.0 mg/kg of Vectibixand FOLFOX4 once every two weeks (Q2W) or FOLFOX4 alone Q2W. The primaryendpoint of the study is progression-free survival by KRAS status andsecondary endpoints include overall survival, objective response rate, time toprogression, duration of response and safety.