Metastatic colorectal cancer first-line treatment with bevacizumab: the impact of K-ras mutation

Luigi Rossi,^1,2 Enzo Veltri,³ Angelo Zullo,⁴ Federica Zoratto,¹ Maria Colonna,⁵ Flavia Longo,⁶ Marcella Mottolese,⁷ Diana Giannarelli,⁸ Luigi Ruco,⁹ Paolo Marchetti,¹⁰ Adriana Romiti,¹⁰ Viola Barucca,¹⁰ Giuseppe Giannini,¹¹ Loredana Bianchi,¹ Silverio Tomao<sup>1

1</sup>Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy; ²Oncology Unit, ICOT Hospital, Latina, Italy; ³Oncology Unit, SM Goretti Hospital, Latina, Italy; ⁴Gastroenterology and Digestive Endoscopy Unit, Nuovo Regina Margherita Hospital, Rome, Italy; ⁵Oncology Unit, Don Luigi di Liegro Hospital, Gaeta, Italy; ⁶Oncology Unit, Umberto I Policlinico di Roma Hospital, Sapienza University of Rome, Rome, Italy; ⁷Department of Pathology, ⁸Biostatistics and Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy; ⁹Department of Pathology, ¹⁰Oncology Unit, Sant'Andrea Hospital, ¹¹Department of Pathology, Umberto I Policlinico di Roma Hospital, Sapienza University of Rome, Rome, Italy

Background: Bevacizumab plus chemotherapy prolongs progression-free survival (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC). Although there is strong evidence to suggest that the mutational status of the K-ras oncogene has a role as a predictive factor for activity in patients treated with cetuximab and panitumumab, few data have been obtained in patients treated with bevacizumab. We conducted an additional retrospective analysis to investigate the prognostic value of K-ras mutation relative to mCRC first-line treatment with bevacizumab.
Materials and methods: A total of 108 patients were retrospectively reviewed. K-ras status was assessed in the overall population by sequencing. Statistical association for PFS and OS was analyzed using the Kaplan–Meier method, and the prognostic role of K-ras was determined using the logrank test.
Results: Median PFS was 10 months both for patients with wild-type (WT) K-ras and mutated (MT) K-ras (hazard ratio [HR] 0.94, P=0.75); neither difference in median OS was significant (27 months WT K-ras versus 26 months MT K-ras, HR 0.92; P=0.70). A further analysis was carried out in the two groups according to metastatic sites. No statistically significant difference in terms of PFS and OS was demonstrated between WT K-ras and MT K-ras with liver metastases only and in those with extrahepatic disease.
Conclusion: Although further study is required, our results seem to confirm that K-ras mutation does not have a prognostic role in mCRC patients receiving first-line treatment with bevacizumab.

Keywords: K-ras, bevacizumab, prognostic factor, metastatic colorectal cancer, liver metastases, extrahepatic disease