Efficacy and safety of CetuGEX in recurrent/metastatic squamous cell carcinoma of the head and neck (RM-HNSCC): Results from the randomized phase II RESGEX study
| Autor: | Bozena Kukielka-Budny, Alina Turcu, Philippe Debourdeau, Sylvie Rottey, Alfredo Zurlo, Cristina-Marinela Oprean, Andrzej Kawecki, Ulrich Keilholz, B. Zurawski, Javier Lavernia, Anca C. Mihailov, Bruno Dietrich, Jérôme Fayette, Ilaria Imarisio, Andreas Dietz, Simona Mihutiu, Gunnar Folprecht, Michael Schenker, Philippe Schafhausen, Sebastian Ochenduszko |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Antibody-dependent cell-mediated cytotoxicity Cisplatin Cancer Research medicine.medical_specialty Cetuximab biology business.industry Standard treatment medicine.disease Primary tumor 03 medical and health sciences 030104 developmental biology Internal medicine Clinical endpoint medicine biology.protein Epidermal growth factor receptor Antibody business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 36:59-59 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 59 Background: Standard treatment for RM-HNSCC is a combination of cisplatin (P), 5-FU (F), and the epidermal growth factor receptor (EGFR) blocking monoclonal antibody cetuximab. CetuGEX is a new monoclonal antibody sharing the identical EGFR-binding domain with cetuximab, but a modified Fc part by a proprietary glycosylation method to optimize antibody dependent cellular cytotoxicity (ADCC). Methods: Patients with RM-HNSCC without relevant comorbidities were randomized to receive up to 6 cycles of P 100 mg/m2, F 4 x 1000 mg/m2/24hrs and CetuGEX vs. cetuximab. Initial dose of cetuximab was 400mg/m2, followed by weekly 250 mg/m2. CetuGEX was given as 990 mg, followed by weekly 720 mg. After end of combination treatment, patients received single agent antibody maintenance until disease progression or intolerable toxicity. Stratification factors included FcγRIIIa status, primary tumor site, EGFR pretreatment vs. naïve, and recurrent vs. metastatic disease. Primary endpoint was progression-free survival (PFS) by immune related response criteria (irRC). Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR) and overall survival (OS) as well as safety and QoL. Results: During Jan 2014 and Feb 2016, 240 patients were accrued in 34 European centers, of which 123 received cetuximab and 117 CetuGEX. The median follow-up was 15 month until May 2017. No difference was observed for the primary endpoint of PFS by irRC [median 27.7 (CetuGEX) and 26.4 (cetuximab) weeks; HR 1.003; 95%-CI 0.738 – 1.363; p = 0.98]. No advantage of CetuGEX over cetuximab was observed for all other secondary efficacy endpoints and subgroup analyses by stratification factors. Infusion related reactions (IRR) were higher for CetuGEX (38.8%) than for cetuximab (5.7%) (Pearson chi2= 37.08; p < 0.0001), but without sequelae. Conclusions: The RESGEX study is the first head-to-head comparison of an ADCC-optimized to a conventional EGFR-directed antibody. The study failed to show superior efficacy of CetuGEX over cetuximab. Both compounds appear to have the same efficacy and a similar safety profile. Glycosylation changes in the Fc part induced more IRRs. Clinical trial information: NCT02052960. |
| Databáze: | OpenAIRE |
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