Abstract 1790
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.
Resources from the same session
3180 - Genomic analysis of hepatobiliary lithiasis associated cholangiocarcinoma revealed a distinct subtype feature.
Presenter: Lunda Gu
Session: Poster Display session 2
Resources:
Abstract
4891 - Comparison of the impact of stereotactic body radiation therapy vs. radiofrequency ablation on liver function in patients with single hepatocellular carcinoma: A propensity score matching analysis
Presenter: Masayuki Ueno
Session: Poster Display session 2
Resources:
Abstract
3203 - Exploratory analysis based on tumor location and early metabolic tumor response of REACHIN, a randomized double-blinded placebo-controlled phase II trial of regorafenib after failure of gemcitabine/platinum-based chemotherapy for advanced and metastatic biliary tract tumors.
Presenter: Anne Demols
Session: Poster Display session 2
Resources:
Abstract
1602 - Predictive Value of Neutrophil-Lymphocyte Ratio (NLR) And Platelet-Lymphocyte Ratio (PLR) In Hepatocellular Carcinoma (HCC) Patients Treated with Nivolumab (N)
Presenter: Sirish Dharmapuri
Session: Poster Display session 2
Resources:
Abstract
2848 - Preliminary Safety and Pharmacokinetics of a New Lysosomotropic Oral Agent, GNS561, in a First-in-Human Study in Advanced Primary Liver Cancer Patients
Presenter: Ahmad Awada
Session: Poster Display session 2
Resources:
Abstract
1396 - A phase 1b trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC): updated results
Presenter: Josep Llovet
Session: Poster Display session 2
Resources:
Abstract
1139 - Multicentric prospective study of validation of angiogenesis-related gene polymorphisms in HCC patients treated with sorafenib: Final results of INNOVATE study
Presenter: Andrea Casadei-gardini
Session: Poster Display session 2
Resources:
Abstract
4688 - Prognostic and predictive factors from the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (aHCC)
Presenter: Tim Meyer
Session: Poster Display session 2
Resources:
Abstract
1492 - A phase Ib study of pembrolizumab following trans-arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): PETAL.
Presenter: David Pinato
Session: Poster Display session 2
Resources:
Abstract
3159 - Anlotinib for advanced hepatocellular carcinoma: interim results from the phase II ALTER0802 study
Presenter: AiPing Zhou
Session: Poster Display session 2
Resources:
Abstract