Dirk L Kienle1, Daniel Dietrich2, Karin Ribi3, Andreas Wicki4, Luca Quagliata4, Ralph C Winterhalder5, Dieter Koeberle6, Daniel Horber7, Sara Bastian8, Marc Kueng9, Piercarlo Saletti10, Daniel Helbling11, Daniela Baertschi2, Alessandro Lugli12, Juerg Bernhard13, Christiane Andrieu2, Roger von Moos8. 1. Kantonsspital Graubünden, Chur, und Universitätsklinikum Ulm, Switzerland. Electronic address: DirkLars.Kienle@ksgr.ch. 2. Swiss Group for Clinical Cancer Research, Coordinating Center, Bern, Switzerland. 3. International Breast Cancer Study Group, Bern, Switzerland. 4. Universitätsspital Basel, Basel, Switzerland. 5. Kantonsspital Luzern, Luzern, Switzerland. 6. Claraspital Basel, Basel, Switzerland. 7. Kantonsspital, St. Gallen, Switzerland. 8. Kantonsspital Graubünden, Chur, und Universitätsklinikum Ulm, Switzerland. 9. Hôpital Fribourgeois, Fribourg, Switzerland. 10. Instituto Oncologia della Svizzera Italiana, Bellinzona, Switzerland. 11. Onkozentrum AG, Zuerich, Zürich, Switzerland. 12. Inselspital, Bern University Hospital, Bern, Switzerland. 13. International Breast Cancer Study Group, Bern, Switzerland; Inselspital, Bern University Hospital, Bern, Switzerland.
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.
RCT Entities:
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.
Authors: Lauren C Bylsma; Rebecca Dean; Kimberly Lowe; Laura Sangaré; Dominik D Alexander; Jon P Fryzek Journal: Cancer Med Date: 2019-08-03 Impact factor: 4.452