1. Cetuximab monotherapy and cetuximab plus capecitabine as first-line treatment in older patients with RAS- and BRAF wild-type metastatic colorectal cancer. Results of the multicenter phase II trial SAKK 41/10
- Author
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Juerg Bernhard, Daniela Baertschi, Roger von Moos, Piercarlo Saletti, Alessandro Lugli, Christiane Andrieu, Luca Quagliata, Dieter Koeberle, Daniel Dietrich, Andreas Wicki, Sara Bastian, D. Helbling, Marc Kueng, Ralph Winterhalder, Dirk L. Kienle, Karin Ribi, and Daniel Horber
- Subjects
Male ,Proto-Oncogene Proteins B-raf ,Oncology ,medicine.medical_specialty ,Bevacizumab ,Colorectal cancer ,Cetuximab ,GTP Phosphohydrolases ,law.invention ,Proto-Oncogene Proteins p21(ras) ,Capecitabine ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,030212 general & internal medicine ,Progression-free survival ,Neoplasm Metastasis ,610 Medicine & health ,Aged ,Aged, 80 and over ,business.industry ,Patient Selection ,Incidence (epidemiology) ,Carcinoma ,Liver Neoplasms ,Membrane Proteins ,medicine.disease ,Progression-Free Survival ,Clinical trial ,030220 oncology & carcinogenesis ,Early Termination of Clinical Trials ,570 Life sciences ,biology ,Female ,Geriatrics and Gerontology ,Colorectal Neoplasms ,business ,medicine.drug - Abstract
Introduction While the anti-VEGF antibody bevacizumab was studied repeatedly as part of low-intensity regimens in less fit elderly patients with metastatic colorectal cancer (mCRC), anti-EGFR antibodies as upfront treatment modality have been scarcely investigated. Material and Methods In SAKK 41/10, the benefit of cetuximab, either alone or in combination with capecitabine, was evaluated in vulnerable elderly patients with RAS/BRAF-wild-type mCRC. Results and Discussion The trial was stopped prematurely due to slow accrual after the inclusion of 24 patients (11 in the monotherapy arm, 13 in the combination arm). Median patient age was 80 years (range 71–89), median CIRS-G score 7 (range 2–13), and median IADL score 7 (range 3–8). At week 12, 6 of 11 patients (55%) were progression-free in the cetuximab monotherapy arm and 9 of 13 patients (69%) in the combination arm. Response rate was 9% in the monotherapy arm and 38% combination arm. The 6 patients with right-sided primary tumors were not responsive to cetuximab. NGS revealed additional mutations affecting the RAS/RAF/MAP kinase pathway in 5 patients; 4 of these patients showed early disease progression. Cetuximab was generally well tolerated and a trend toward an improvement of symptom-related QoL was observed. In the combination arm, a higher incidence of toxicities and treatment stoppings was observed. In conclusion, trial recruitment – requiring both geriatric as well as molecular eligibility criteria – proved more difficult than expected. Bearing in mind the very small sample size, upfront cetuximab treatment appeared tolerable and showed promising activity in left-sided tumors in both treatment arms.
- Published
- 2019
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