The addition of the targeted therapy Vectibix® (panitumumab) to chemotherapy improves progression-free survival in patients with newly diagnosed or previously treated metastatic colorectal cancer. The benefit only applies to the subset of patients whose cancer does not contain a mutation in the KRAS gene. The results of these Phase III clinical trials were published in the Journal of Clinical Oncology.

Colorectal cancer remains the second leading cause of cancer-related death in the United States. Metastatic colorectal cancer refers to cancer that has spread from the colon to distant sites in the body.

Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target,” targeted therapies may slow cancer cell growth or increase cancer cell death.

Vectibix inhibits cancer cell growth and survival by targeting a protein known as the epidermal growth factor receptor (EGFR). Vectibix has been approved for the treatment of EGFR-expressing metastatic colorectal cancer that has progressed on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Vectibix appears to benefit only those patients whose cancers do not contain a mutation in a gene known as KRAS. KRAS mutations occur in an estimated 40-50% of metastatic colorectal cancers and can be identified by testing a sample of tumor tissue.

Two recently published Phase III clinical trials reported on the safety and efficacy of Vectibix in combination with chemotherapy for metastatic colorectal cancer. One of the trials evaluated Vectibix in the first-line (initial) treatment of metastatic colorectal cancer, and the other evaluated Vectibix in the second-line treatment of metastatic colorectal cancer.

The study that evaluated Vectibix in newly diagnosed, metastatic colorectal cancer was known was PRIME (Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy).[1] The study enrolled 1,183 patients. Study participants were assigned to receive treatment with FOLFOX4 chemotherapy alone or FOLFOX4 plus Vectibix.

• Among patients without KRAS mutations, the addition of Vectibix delayed cancer progression. Progression-free survival was 9.6 months among patients treated with chemotherapy plus Vectibix compared with 8.0 months among patients treated with chemotherapy alone. Overall survival was 23.9 months among patients treated with chemotherapy plus Vectibix versus 19.7 months among patients treated with chemotherapy alone, but this result did not meet the criteria for statistical significance, suggesting that it could have occurred by chance alone.
• Among patients with KRAS mutations, the addition of Vectibix worsened outcomes. Progression-free survival was 7.3 months among patients treated with chemotherapy plus Vectibix compared with 8.8 months among patients treated with chemotherapy alone.

To evaluate the effectiveness of Vectibix in the second-line treatment of metastatic colorectal cancer, researchers conducted a Phase III clinical trial among 1,186 previously treated patients.[2] Study participants were assigned to receive treatment with FOLFIRI chemotherapy alone or FOLFIRI plus Vectibix.

• Among patients without KRAS mutations, progression-free survival was 5.9 months among patients treated with chemotherapy plus Vectibix compared with 3.9 months among patients treated with chemotherapy alone. Overall survival was 14.5 months among patients treated with chemotherapy plus Vectibix versus 12.5 months among patients treated with chemotherapy alone, but this result did not meet the criteria for statistical significance, suggesting that it could have occurred by chance alone.
• Among patients with KRAS mutations, the addition of Vectibix did not improve progression-free or overall survival.

In both studies, side effects of Vectibix included skin rash, low magnesium levels, and diarrhea.

These studies indicate that the addition of Vectibix to chemotherapy delays cancer progression among patients with either newly diagnosed or previously treated metastatic colorectal cancer. Because the benefit only applies to patients whose cancer does not contain a KRAS mutation, these studies also highlight the importance of KRAS testing prior to treatment with this type of targeted therapy.

References:

[1] Douillard J-Y, Siena S, Cassidy J et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. Journal of Clinical Oncology [early online publication]. October 4, 2010.

[2] Peeters M, Price TJ, Cervantes A et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. Journal of Clinical Oncology [early online publication]. October 4, 2010.

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