J Cancer 2019; 10(24):5926-5934. doi:10.7150/jca.34550

Research Paper

Impact of primary tumor location in patients with RAS wild-type metastatic colon cancer treated with first-line chemotherapy plus anti-EGFR or anti-VEGF monoclonal antibodies: a retrospective multicenter study

Antonino Grassadonia1✉, Pietro Di Marino2, Corrado Ficorella3, Alessio Cortellini3, Katia Cannita3, Alessandro Parisi3, Teresa Gamucci4, Federica Zoratto5, Patrizia Vici6, Maddalena Barba6, Ettore Porreca2, Matteo Neri7, Angelo Veronese7, Clara Natoli1, Michele De Tursi2, Nicola Tinari1

1. Department of Medical, Oral & Biotechnological Sciences and CeSI-MeT, G. D'Annunzio University, Chieti-Pescara, Italy
2. Department of Medical, Oral & Biotechnological Sciences, G. D'Annunzio University, Chieti-Pescara, Italy
3. Medical Oncology Unit, St Salvatore Hospital, Department of Biotechnological & Applied Clinical Sciences, University of L'Aquila, Via Vetoio, 67100, L'Aquila, Italy.
4. Medical Oncology Unit, Sandro Pertini Hospital, Rome, Italy.
5. Medical Oncology Unit, F. Spaziani Hospital, Frosinone, Italy.
6. Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
7. Department of Medicine and Ageing Sciences and CeSI-MeT, G. D'Annunzio University, Chieti, Italy.

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Citation:
Grassadonia A, Di Marino P, Ficorella C, Cortellini A, Cannita K, Parisi A, Gamucci T, Zoratto F, Vici P, Barba M, Porreca E, Neri M, Veronese A, Natoli C, De Tursi M, Tinari N. Impact of primary tumor location in patients with RAS wild-type metastatic colon cancer treated with first-line chemotherapy plus anti-EGFR or anti-VEGF monoclonal antibodies: a retrospective multicenter study. J Cancer 2019; 10(24):5926-5934. doi:10.7150/jca.34550. Available from http://www.jcancer.org/v10p5926.htm

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Abstract

Emerging evidence supports a prognostic role of primary tumor location in metastatic colon cancer (mCC). We conducted a retrospective analysis to evaluate the effect of tumor location on prognosis and efficacy of biological agents (anti-EGFR, Cetuximab and Panitumumab, or anti-VEGF, Bevacizumab) added to first-line chemotherapy in patients with RAS wild-type (wt) mCC. Patients with newly diagnosed RAS wt mCC candidates to first-line chemotherapy with anti-EGFRs or Bevacizumab were selected. Clinical outcomes were assessed and stratified by tumor location and type of treatment. Overall, 351 patients met the inclusion criteria. Primary colon cancer was right-sided (RCC) in 105 (29.9%) patients and left-sided (LCC) in 246 (70.1%). Patients with LCC had a better OS compared to those with RCC (33.6 vs 23.5 months, HR 0.74; 95% CI, 0.55 to 0.99; p=0.049). In the overall study population, OS was not significantly different for patients treated with Cetuximab or Panitumumab as compared to those receiving Bevacizumab. However, when comparing treatment outcome according to tumor sidedness, patients with LCC treated with Cetuximab or Panitumumab had a significantly longer PFS (12.4 vs 10.7 months; HR: 0.69; 95% CI, 0.51 to 0.93; p= 0.015) and OS (40.7 vs 28.6 months; HR: 0.67; 95% CI 0.47 to 0.95; p= 0.026). No relevant differences were observed in patients with RCC.

We found evidence in support of the impact of tumor location in RAS wt mCC treated with first-line chemotherapy in association with targeted therapy. More favorable outcomes were observed in LCC patients, but not in RCC patients, treated with anti-EGFR agents compared with those who received Bevacizumab. Further, prospective and adequately sized studies are warranted to confirm our findings.

Keywords: Metastatic colorectal cancer (mCRC), RAS wt, Tumor location, Cetuximab, Panitumumab, Bevacizumab