Amgen will continue ongoing studies of Vectibix (panitumumab) after halting a study that tested the effectiveness of the EGFR inhibitor in combination with Genentech's VEGF inhibitor Avastin (bevacizumab) plus chemotherapy, the company said March 22.

"The key distinction between those ongoing trials and the PACCE trial is that PACCE was really looking at what happens when you use dual biologics together with chemotherapy, and our registrational studies are looking just at Vectibix with chemotherapy" for metastatic colorectal cancer, Amgen told "The Pink Sheet" DAILY.

The Panitumumab Advanced Colorectal Cancer Evaluation study in first-line treatment of mCRC was halted after an interim efficacy analysis conducted after the first 231 events (death or disease progression) revealed a statistically significant benefit in progression-free survival, the primary endpoint of the study, in favor of the control arm, Amgen said.

Interim 12-week data from PACCE released in January showed responses in the first 500 patients were similar in both treatment arms (¹ Also see "Vectibix Vs. Erbitux: The Race For A First-Line Colorectal Cancer Indication" - Pink Sheet, 26 January, 2007.).

In addition, the analysis signaled an apparent increase in toxicity from the dual biologics combination.

Amgen also pointed out in January that the interim analysis showed an increased incidence of grade 3 severe events of diarrhea, dehydration and infections in the Vectibix-treated patients, as well as an increased incidence of pulmonary embolism (one of them fatal) in patients who received panitumumab (4 percent) compared with those who did not (2 percent).

The open-label randomized PACCE trial enrolled 1,054 patients at 240 U.S. trial sites between the first quarter of 2005 and the third quarter of 2006.

Vectibix was approved in September 2006 for treatment of EGFR-expressing mCRC following chemotherapy based on the surrogate endpoint of progression-free survival (² Also see "Amgen Vectibix Approved For Metastatic Colorectal Cancer" - Pink Sheet, 27 September, 2006.).

Approval was based on a 463-patient randomized study that yielded a mean time-to-disease progression or death at 96 days with Vectibix versus 60 days in patients receiving standard supportive care. Review documents reveal that FDA reviewers were puzzled that the study did not show clearly that an effect on PFS resulted in an effect on overall survival and that medical and statistical reviewers differed in their opinions why (³ Also see "FDA Vectibix Review Posits Study Design Issues That Could Have Led To Lack Of Survival Benefit" - Pink Sheet, 19 March, 2007.).

Amgen's postmarketing commitment for Vectibix includes a Phase III study to verify the therapy's clinical benefit through demonstration of an effect on overall survival. That confirmatory trial evaluating Vectibix plus chemotherapy in second-line mCRC is enrolling 1,100 patients globally.

Another trial evaluating Vectibix with chemotherapy as a first-line mCRC therapy is enrolling 900 patients globally.

In January, Bristol-Myers Squibb/ImClone, developers of Amgen's competitor in the mCRC space, Erbitux (cetuximab), announced positive Phase III results for the EGFR agent in combination with chemotherapy in the first-line treatment of the disease (⁴ Also see "ImClone Reports Promising Erbitux First-Line Colorectal Cancer Results" - Pink Sheet, 10 January, 2007.). Avastin already has a first-line colorectal cancer indication.

ImClone also is testing its therapy in combination with Avastin. Data from a Phase III study are expected early this year.

- Shirley Haley (s.haley@elsevier.com)

Amgen’s Colorectal Cancer Program Proceeding Despite Vectibix PACCE Failure

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