KRAS Status Makes Significant Difference in Outcomes With Cetuximab in Colorectal Cancer: Presented at ASCO

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Title: KRAS Status Makes Significant Difference in Outcomes With Cetuximab in Colorectal Cancer: Presented at ASCO
URL: http://www.pslgroup.com/dg/222F42.htm
Doctor's Guide
June 4, 2008

By Ed Susman

CHICAGO -- June 4, 2008 -- When genetic status of patients is considered, the use of cetuximab with chemotherapy sharply improved outcomes among metastatic colorectal cancer patients, researchers said here at the American Society of Clinical Oncology (ASCO) 44th Annual Meeting.

The benefit for patients with the wild-type oncogene known as v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) was clearly significantly different -- with high significance," said Carsten Bokemeyer, MD, Universitatsklinikum Eppendorf, Hamburg, Germany.

In contrast, Dr. Bokemeyer said, when patients harboured a mutant KRAS gene, "it was somewhat the other way around."

Dr. Bokemeyer presented the results of his analysis on June 1 of the Oxaliplatin and Cetuximab in First-Line Treatment of Metastatic Colorectal Cancer study, which recruited 337 patients with metastatic colorectal cancer.

In the study, patients were treated with a combination of oxaliplatin 85 mg/m² per day every 2 weeks, leucovorin 200 mg/m² on days 1 and 2, and 5-fluorouracil 400 mg/m² bolus with 600 mg/m² infusion over 22 hours on days 1 and 2 (FOLFOX4). In addition, patients were divided into 2 groups: group A received cetuximab 400 mg/m² initial IV infusion on day 1 then 250 mg/m² weekly and group B did not receive cetuximab.

Initial efficacy analysis showed a trend favouring the cetuximab combination for response rate. Response rates were 45.6% in the cetuximab plus FOLFOX4 group and 35.7% among patients treated with FOLFOX4 alone (P = .064). Progression-free survival was 7.2 months in both treatment groups.

Dr. Bokemeyer said that KRAS gene mutations are found in 40% to 50% of patients with colorectal cancer and are generally associated with poor prognosis. A number of earlier clinical studies previously suggested that such mutations may be behind lack of response to endothelial growth factor receptor inhibitors such as cetuximab.

When he and his team analysed the data separately for patients with and without KRAS mutations, they found a significant advantage with cetuximab in patients who did not have the mutation.

In OPUS, 134 patients -- about 58% of the total in the trial who were evaluable -- expressed a wild-type KRAS gene; 99 patients with KRAS mutations were identified.

Dr. Bokemeyer found response rates in the KRAS wild-type patients to be 37% for FOLFOX4 and 61% for FOLFOX4 plus cetuximab (P = .011). For those with the KRAS mutation, there was no significant difference between treatments; about 49% of the FOLFOX4 patients responded compared with 33% of patients in the FOLFOX4 plus cetuximab group (P = .106).

The same pattern emerged for median progression-free survival with in patients with KRAS wild-type (7.2 months for FOLFOX vs 7.7 months for FOLFOX4 plus cetuximab, P = .016). Among those with the KRAS mutation median progression free survival was 8.6 and 5.5 months, respectively (P = .0192).

Dr. Bokemeyer noted that there were no differences between treatments in duration of treatment or relative dose intensity. Also, there were no differences in the most common grade 3 or 4 adverse events.

[Presentation title: KRAS Status and Efficacy of First-Line Treatment of Patients With Metastatic Colorectal Cancer With FOLFOX With or Without Cetuximab: The OPUS Experience. Abstract 4000]

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