domingo, 29 de septiembre de 2013

Panitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer — NEJM

Panitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer — NEJM


Panitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer

Jean-Yves Douillard, M.D., Ph.D., Kelly S. Oliner, Ph.D., Salvatore Siena, M.D., Josep Tabernero, M.D., Ronald Burkes, M.D., Mario Barugel, M.D., Yves Humblet, M.D., Ph.D., Gyorgy Bodoky, M.D., Ph.D., David Cunningham, M.D., Jacek Jassem, M.D., Ph.D., Fernando Rivera, M.D., Ph.D., Ilona Kocákova, M.D., Ph.D., Paul Ruff, M.D., Maria Błasińska-Morawiec, M.D., Martin Šmakal, M.D., Jean Luc Canon, M.D., Mark Rother, M.D., Richard Williams, M.B., B.S., Ph.D., Alan Rong, Ph.D., Jeffrey Wiezorek, M.D., Roger Sidhu, M.D., and Scott D. Patterson, Ph.D.
N Engl J Med 2013; 369:1023-1034September 12, 2013DOI: 10.1056/NEJMoa1305275
Abstract
Article
References
Citing Articles (1)

Background

Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti–epidermal growth factor receptor (EGFR) therapy. Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy.

Methods

In this prospective–retrospective analysis, we assessed the efficacy and safety of panitumumab plus oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) as compared with FOLFOX4 alone, according to RAS (KRAS or NRAS) or BRAF mutation status. A total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2 had results for at least one of the following: KRAS exon 3 or 4; NRAS exon 2, 3, or 4; or BRAF exon 15. The overall rate of ascertainment of RAS status was 90%.

Results

Among 512 patients without RAS mutations, progression-free survival was 10.1 months with panitumumab–FOLFOX4 versus 7.9 months with FOLFOX4 alone (hazard ratio for progression or death with combination therapy, 0.72; 95% confidence interval [CI], 0.58 to 0.90; P=0.004). Overall survival was 26.0 months in the panitumumab–FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group (hazard ratio for death, 0.78; 95% CI, 0.62 to 0.99; P=0.04). A total of 108 patients (17%) with nonmutated KRAS exon 2 had other RAS mutations. These mutations were associated with inferior progression-free survival and overall survival with panitumumab–FOLFOX4 treatment, which was consistent with the findings in patients with KRAS mutations in exon 2. BRAF mutations were a negative prognostic factor. No new safety signals were identified.

Conclusions

Additional RAS mutations predicted a lack of response in patients who received panitumumab–FOLFOX4. In patients who had metastatic colorectal cancer without RAS mutations, improvements in overall survival were observed with panitumumab–FOLFOX4 therapy. (Funded by Amgen and others; PRIME ClinicalTrials.gov number, NCT00364013.)

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