Amgen halts clinical trial combining chemotherapy with Avastin and Vectibix

Amgen has discontinued the PACCE clinical trial which was evaluating adding Vectibix® (panitumumab) to standard first-line treatment for metastatic colorectal cancer.  The PACCE trial randomly assigned patients to receive chemotherapy and Avastin®(bevacizumab) or chemotherapy plus both Avastin® and Vectibix®.

An early analysis built into the trial showed that patients in the standard therapy control arm had better progression-free survival that those in the experimental arm that included Vectibix.  Further analysis also showed better overall survival for the control arm.  Additional study of the trial is underway, and Amgen plans to present the information at an upcoming scientific meeting.

Amgen has let research physicians whose patients are enrolled in the PACCE trial know that Vectibix should be discontinued for those in the experimental arm of the study.  Patients will have the option of continuing the study on chemotherapy and Avastin alone.

In January 2007, Amgen reported an interim safety analysis of the trial that showed increased diarrhea, dehydration, and infection for those patients whose treatment plan included Vectibix.  There were also more cases of blood clots in the lungs (pulmonary embolism) in the Vectibix arm — 4 percent versus 2 percent.  One patient receiving Vectibix died of pulmonary embolism.

Roger M. Perlmutter, M.D. Ph.D., executive vice president of Research and Development at Amgen said,

Patient safety is Amgen’s top priority. For this reason, we have decided to discontinue Vectibix treatment in the PACCE trial while we complete additional analyses of these preliminary results. We had hoped that adding Vectibix to the current U.S. standard-of-care for patients newly-diagnosed with metastatic colorectal cancer would improve outcomes without excessive added toxicity. Unfortunately, it appears that adding Vectibix to Avastin, when used in combination with oxaliplatin- or irinotecan-based chemotherapy, increased toxicity, without improving efficacy.

Vectibix is a monoclonal antibody which blocks the epidermal growth factor.  It is currently approved by the FDA to treat patients whose colon or rectal cancer has progressed on standard treatments.  Compared to the best supportive therapy, Vectibix, as a single drug, increased the time that cancer did not progress.

Amgen will continue enrolling patients in trials where Vectibix is the only monoclonal antibody added to chemotherapy including:

• Phase III study to compare FOLFIRI with Vectibix to FOLFIRI alone for second-line treatment of metastatic colorectal cancer.
• PRIME: Phase III study comparing FOLFOX with Vectibix to FOLFOX alone for first-line treatment of metastatic colorectal cancer.

WHAT THIS MEANS FOR PATIENTS

Combining chemotherapy and Avastin with Vectibix led to poorer outcomes for patients having their first treatment for stage IV or recurrent colon or rectal cancer (metastatic colorectal cancer.)

Patients on who received Vectibix in addition to chemo with Avastin had their cancer get worse more quickly (progression-free survival) and also had shorter survival time (overall survival).

Earlier analysis of side effects found that including Vectibix increased serious diarrhea, dehydration, infection, and blood clots in the lungs.

Overall, adding Vectibix to standard chemotherapy with FOLFOX or FOLFIRI plus Avastin resulted in more toxicity and less effectiveness.

Patients who are part of the PACCE trial should stop using Vectibix if they are on the experimental arm of the trial.  They can continue the trial with chemotherapy and Avastin alone.

Vectibix is not labeled for use with Avastin and chemotherapy.  It is labeled to be used alone (as monotherapy) for refractory patients who have progressed on standard therapy. Its use for treatments other than those that are currently FDA-labeled should be limited to clinical trials.

We have no information from this trial about whether a similar EGFR inhibitor, Erbitux® (cetuximab), would have similar outcomes.

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