1790 - Impact of prophylactic systemic antibiotics (SA) on outcome of patients (pts) with RAS-wildtype (RAS-wt) metastatic colorectal carcinoma (mCRC) treated with cetuximab-based first-line therapy. Subgroup analysis of the german non-interventional study ERBITAG

Background

SA are widely used and recommended to ameliorate skin reactions induced by EGFR inhibition. Randomised studies have shown a positive impact of SA on severity of skin reactions, but the influence on outcome are widely unknown. Recent data suggests that antibiotics negatively influence the efficacy of checkpoint-inhibitor therapies. Therefore, an evaluation of the impact of SA on the outcome of RAS-wt mCRC pts treated with cetuximab-based therapy is highly needed.

Methods

Pts with RAS-wt mCRC treated with a cetuximab-based first-line combination and written informed consent were eligible for this prospective, non-interventional study. According to a thorough questionnaire about prophylactic treatments for skin management, pts were categorized in 2 groups: SA and no SA. Outcome endpoints like objective remission rate (ORR), progression free survival (PFS), overall survival (OS), and time to treatment failure (TTF) were compared between the two subgroups.

Results

Data from 583 of 875 enrolled pts were evaluable at the data cut-off (SA: n = 183; no SA: n = 400). Pts were not included for the following reasons: no cetuximab therapy (34), not fully documented (131), no first-line therapy (95), no RAS-wt (2), and no skin questionnaire (30). Pts in the SA group showed compared to the no SA group a significantly increased median PFS with 12.30 vs 9.51 months (p = 0.033) and OS with 28.22 vs. 20.79 months (p = 0.0063). Number of cetuximab infusions were numerically higher in the SA group (mean: 30.6 vs 27.4, p = 0.0581), as well as ORR with 63.9% and 56.5% (p = 0.09) and TTF with 5.46 vs 4.61 months (p = 0.0746), but all three endpoints did not reach significance. In a multivariate analysis the impact of SA was an independent significant factor on OS (p < 0.05), but not on PFS (p = 0.09).

Conclusions

Data of this large non-interventional trial suggests that SA have a positive impact on the OS outcome of RAS-wt mCRC pts treated with a cetuximab-based first-line therapy. Hence, the data supports the recommendations for SA in the treatment management of EGFR inhibitors in mCRC.

Clinical trial identification

Editorial acknowledgement

Felix Eilenberger, Alcedis GmbH, Gießen, Germany.

Legal entity responsible for the study

Merck Serono GmbH, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany.

Funding

Merck Serono GmbH, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany.

Disclosure

S.W. Sahm: Shareholder / Stockholder / Stock options: Merck KGaA; Honoraria (self): Fresenius Kabi; Research grant / Funding (institution): Merck Serono GmbH. M. Zahn: Honoraria (self): Merck Serono GmbH. J. Janssen: Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Research grant / Funding (institution): PharmaMar; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Onyx; Research grant / Funding (institution): Baxter; Research grant / Funding (institution): Biotest; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Janssen Cilag Ltd; Research grant / Funding (institution): Kedrion Biopharma; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Merck Serono GmbH; Research grant / Funding (institution): Octapharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Puma Biotechnology; Research grant / Funding (institution): Teva Pharmaceutical; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Servier. C. Hering-Schubert: Honoraria (self): Novartis; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self): Sanofi. I. Zander: Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self): Pfizer; Honoraria (self): Mundipharma; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Ribosepharm; Travel / Accommodation / Expenses: Merck Serono GmbH. K.G. Stenzel: Full / Part-time employment: Merck Serono GmbH; Shareholder / Stockholder / Stock options: Merck KGaA. F. Overkamp: Leadership role, Full / Part-time employment: OncoConsult. Hamburg GmbH; Leadership role, Full / Part-time employment: onkowissen.de GmbH; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self): AstraZeneca; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Cellex; Advisory / Consultancy: ClinSol; Honoraria (self), Advisory / Consultancy: Gilead; Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: Iomedico; Honoraria (self), Advisory / Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Riemser; Advisory / Consultancy: Roche; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Teva; Honoraria (self): Chugai; Honoraria (self): Celgene; Honoraria (self): Eisai; Honoraria (self): Ipsen; Honoraria (self): Janssen-Cilag; Honoraria (self): Merck Serono GmbH; Honoraria (self): Novo Nordisc; Honoraria (self): Servier; Honoraria (self): Shire. All other authors have declared no conflicts of interest.