Amgen Highlights Phase 2 Results Of Vectibix® (panitumumab) Versus bevacizumab In Combination With FOLFOX In Patients With Wild-Type RAS (KRAS And NRAS) Metastatic Colorectal Cancer

THOUSAND OAKS, Calif., May 31, 2014 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced results from the Phase 2 PEAK study that reinforce the improved overall survival (OS) benefit of panitumumab (Vectibix^®) when used in combination with FOLFOX, an oxaliplatin-based chemotherapy regimen, compared to bevacizumab (Avastin^®) plus FOLFOX as first-line treatment in patients with wild-type RAS metastatic colorectal cancer (mCRC). The data was presented today at the 50^th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago (Abstract No. 3629).

The data presented at ASCO was an extended analysis of the PEAK study that supports the use of panitumumab in combination with FOLFOX for patients with wild-type RAS (absence of exons 2, 3, or 4 KRAS or NRAS mutations) mCRC.

In this exploratory analysis, patients who received panitumumab plus FOLFOX and were then treated with a VEGF inhibitor-based treatment (including bevacizumab) had a median OS improvement of 41.3 months. By comparison, patients who received bevacizumab plus FOLFOX and were then treated with an anti-EGFR inhibitor-based treatment (including panitumumab/cetuximab), had a median OS improvement of 29.0 months. For both arms, outcomes were similar to those observed in the overall treated population with wild-type RAS mCRC.

"The initial PEAK data reinforce the potential importance of panitumumab for select patients, but we wanted to evaluate whether this benefit was dependent on administration with FOLFOX and if other subsequent treatments might impact survival outcomes," said Fernando Rivera, M.D., Medical Oncology Department, Hospital Universitario Marques de Valdecilla, Santander, Spain, and a lead investigator in the study. "These data suggest that a front-line treatment strategy with panitumumab in combination with FOLFOX may offer clinical benefit in patients with wild-type RAS metastatic colorectal cancer compared to bevacizumab-based regimens in this treatment setting."

"The PEAK study not only shows the survival benefit of panitumumab in patients who have metastatic colorectal cancer with wild-type KRAS tumors, but also gets us another step closer to understanding how unique genetic markers may change the way we treat cancers," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Every study we conduct as part of our comprehensive panitumumab development program adds to a growing understanding of how to personalize care for cancer patients."

Colorectal cancer is the third most common cancer in the U.S., and is the second leading cause of cancer deaths.^1,2 Approximately 1.2 million cases of colorectal cancer are expected to occur globally.³

About Vectibix^® (panitumumab)
Vectibix is the first fully human anti-EGFR antibody approved by the U.S. Food and Drug Administration (FDA) for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first and only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC.

Important U.S. Product Information
Vectibix is indicated for the treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) mCRC as determined by an FDA-approved test for this use:

• As first-line therapy in combination with FOLFOX
• As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy

Vectibix is not indicated for the treatment of patients with KRAS-mutant mCRC or for whom KRAS mutation status is unknown.

WARNING: DERMATOLOGIC TOXICITY
Dermatologic Toxicity: Dermatologic toxicities occurred in 90 percent of patients and were severe (NCI-CTC grade 3 or higher) in 15 percent of patients receiving Vectibix monotherapy. [See Dosage and Administration (2.1), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].

Determination of KRAS mutational status in colorectal tumors using an FDA-approved test indicated for this use is necessary for selection of patients for treatment with Vectibix.  Patients with KRAS-mutant mCRC tumors receiving Vectibix in combination with FOLFOX experienced shorter OS compared to FOLFOX alone.

Progressively decreasing serum magnesium levels leading to severe (Grade 3-4) hypomagnesemia occurred in up to 7% of patients across clinical trials.  Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix treatment, periodically during Vectibix treatment, and for up to 8 weeks after the completion of treatment.

In a clinical trial, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4).

Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix in combination with chemotherapy.

Fatal and non-fatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix.  Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix.  In the event of acute onset or worsening of pulmonary symptoms, interrupt Vectibix therapy.  Discontinue Vectibix therapy if ILD is confirmed.

The most common adverse reactions of Vectibix are skin rash with variable presentations, paronychia, fatigue, nausea and diarrhea. The most frequently reported serious, adverse reactions of Vectibix are general physical health deterioration, and intestinal obstruction.

The most commonly reported adverse reactions (> 20%) in patients with wild-type KRAS mCRC receiving Vectibix (6 mg/kg every 2 weeks) and FOLFOX therapy (N = 322) in Study 3 were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin.  Serious adverse reactions (≥ 2% difference between treatment arms) in Vectibix-treated patients with wild-type KRAS mCRC were diarrhea and dehydration. 

To see the full Vectibix Safety Information, visit www.vectibix.com.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be the world's largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

Forward-Looking Statements
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Avastin^® is a registered trademark of Genentech, a member of the Roche Group.

CONTACT: Amgen
Cuyler Mayer, 310-353-6199 (media)
Arvind Sood, 805-447-1060 (investors)

References

¹ Colorectal Cancer Facts and Figures. American Cancer Society website.     http://www.cancer.org/cancer/colonandrectumcancer/detailedguide/colorectal-cancer-key-statistics. Accessed March  25, 2013.
²    Colorectal Cancer Prevention (PDQ^®). National Cancer Institute. Accessed March 25, 2013.     http://www.cancer.gov/cancertopics/pdq/prevention/colorectal/HealthProfessional/page3.
³   Jemal. Global Cancer Statistics. CA Cancer J Clin. 2011;61:69-90.

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SOURCE Amgen