PREMIUM: A French prospective multicenter observational study of factors impacting on efficacy and compliance to cetuximab treatment in first-line KRAS wild-type metastatic colorectal cancer

L Mineur, E François, C Plassot, J M Phelip, L Miglianico, L M Dourthe, N Bonichon, L Moreau, R Guimbaud, D Smith, E Achille, R Hervé, J M Bons, S Remy, R Faroux, A L Villing, A Mahamat, I Rabbia, P Soulié, I Baumgaertner, N Mathé, L Vazquez, R Boustany, L Mineur, E François, C Plassot, J M Phelip, L Miglianico, L M Dourthe, N Bonichon, L Moreau, R Guimbaud, D Smith, E Achille, R Hervé, J M Bons, S Remy, R Faroux, A L Villing, A Mahamat, I Rabbia, P Soulié, I Baumgaertner, N Mathé, L Vazquez, R Boustany

Abstract

Background: Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC.

Patients and methods: PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety.

Results: A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies.

Conclusions: ECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients.

Conflict of interest statement

The PREMIUM study was funded by Merck Serono, France., an affiliate of Merck KGaA Darmstadt, Germany. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors declare no financial, non-financial, professional or personal conflict of interest other than the funding of the study.

Figures

Fig 1. Trial profile.
Fig 1. Trial profile.
Fig 2. Kaplan-Meier plot for progression-free survival…
Fig 2. Kaplan-Meier plot for progression-free survival of mCRC patients on first-line cetuximab.

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