Jennifer A Crozier1, Pooja P Advani1, Betsy LaPlant2, Timothy Hobday3, Anthony J Jaslowski4, Alvaro Moreno-Aspitia1, Edith A Perez5. 1. Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL. 2. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN. 3. Division of Medical Oncology, Mayo Clinic, Rochester, MN. 4. Department of Hematology, Green Bay Oncology, Green Bay, WI. 5. Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL. Electronic address: perez.edith@mayo.edu.
Abstract
BACKGROUND: Irinotecan has a 20% to 25% response rate (RR) in patients with previously treated metastatic breast cancer (MBC). Epidermal growth factor receptor (EGFR) is overexpressed in some MBC, especially in triple-negative breast cancer (TNBC). Cetuximab is a monoclonal antibody against EGFR with additive preclinical activity with irinotecan. PATIENTS AND METHODS: We report a 1-stage phase II study on MBC, measurable disease, and previous anthracycline and/or taxane therapy. Patients received cetuximab 400 mg/m(2) on day 1 cycle 1 then 250 mg/m(2) weekly thereafter and irinotecan 80 mg/m(2) on days 1 and 8 of each 21-day cycle. The primary end point was overall RR (ORR) according to Response Evaluation Criteria in Solid Tumors criteria (version 1.1). RESULTS: Of 19 eligible patients enrolled from February to September 2006, 14 patients (74%) had visceral disease, seven patients (37%) were hormone receptor-positive, two patients (11%) HER2-positive, and 11 patients (58%) were triple-negative. Patients received a median of 2 cycles (range, 1-37). Confirmed ORR was 11% (95% confidence interval [CI], 1%-33%), with 1 partial response and 1 complete response. One patient had stable disease for 8 months. RR for TNBC versus non-TNBC was 18% versus 0% (P = .49). Median time to progression was 1.4 months (95% CI, 1.0-2.2) and median overall survival was 9.4 months (95% CI, 2.8-16.1). Twelve patients had disease progression within 2 cycles during therapy. Because of a low RR and rapid disease progression, the study leadership decided to close the trial early. CONCLUSION: The tolerability of the combination of cetuximab and irinotecan is acceptable but demonstrated low overall activity. Potentially promising results were noted in patients with TNBC and further studies of these patients might be considered.
BACKGROUND:Irinotecan has a 20% to 25% response rate (RR) in patients with previously treated metastatic breast cancer (MBC). Epidermal growth factor receptor (EGFR) is overexpressed in some MBC, especially in triple-negative breast cancer (TNBC). Cetuximab is a monoclonal antibody against EGFR with additive preclinical activity with irinotecan. PATIENTS AND METHODS: We report a 1-stage phase II study on MBC, measurable disease, and previous anthracycline and/or taxane therapy. Patients received cetuximab 400 mg/m(2) on day 1 cycle 1 then 250 mg/m(2) weekly thereafter and irinotecan 80 mg/m(2) on days 1 and 8 of each 21-day cycle. The primary end point was overall RR (ORR) according to Response Evaluation Criteria in Solid Tumors criteria (version 1.1). RESULTS: Of 19 eligible patients enrolled from February to September 2006, 14 patients (74%) had visceral disease, seven patients (37%) were hormone receptor-positive, two patients (11%) HER2-positive, and 11 patients (58%) were triple-negative. Patients received a median of 2 cycles (range, 1-37). Confirmed ORR was 11% (95% confidence interval [CI], 1%-33%), with 1 partial response and 1 complete response. One patient had stable disease for 8 months. RR for TNBC versus non-TNBC was 18% versus 0% (P = .49). Median time to progression was 1.4 months (95% CI, 1.0-2.2) and median overall survival was 9.4 months (95% CI, 2.8-16.1). Twelve patients had disease progression within 2 cycles during therapy. Because of a low RR and rapid disease progression, the study leadership decided to close the trial early. CONCLUSION: The tolerability of the combination of cetuximab and irinotecan is acceptable but demonstrated low overall activity. Potentially promising results were noted in patients with TNBC and further studies of these patients might be considered.
Authors: Brian D Lehmann; Joshua A Bauer; Xi Chen; Melinda E Sanders; A Bapsi Chakravarthy; Yu Shyr; Jennifer A Pietenpol Journal: J Clin Invest Date: 2011-07 Impact factor: 14.808
Authors: Nicola Normanno; Antonella De Luca; Caterina Bianco; Luigi Strizzi; Mario Mancino; Monica R Maiello; Adele Carotenuto; Gianfranco De Feo; Francesco Caponigro; David S Salomon Journal: Gene Date: 2005-12-27 Impact factor: 3.688
Authors: Rohit Bhargava; William L Gerald; Allan R Li; Qiulu Pan; Priti Lal; Marc Ladanyi; Beiyun Chen Journal: Mod Pathol Date: 2005-08 Impact factor: 7.842
Authors: Pedro J Real; Adalberto Benito; Jorge Cuevas; Maria T Berciano; Ana de Juan; Paul Coffer; Javier Gomez-Roman; Miguel Lafarga; Jose M Lopez-Vega; Jose L Fernandez-Luna Journal: Cancer Res Date: 2005-09-15 Impact factor: 12.701
Authors: Torsten O Nielsen; Forrest D Hsu; Kristin Jensen; Maggie Cheang; Gamze Karaca; Zhiyuan Hu; Tina Hernandez-Boussard; Chad Livasy; Dave Cowan; Lynn Dressler; Lars A Akslen; Joseph Ragaz; Allen M Gown; C Blake Gilks; Matt van de Rijn; Charles M Perou Journal: Clin Cancer Res Date: 2004-08-15 Impact factor: 12.531
Authors: Giuseppe Viale; Nicole Rotmensz; Patrick Maisonneuve; Luca Bottiglieri; Emilia Montagna; Alberto Luini; Paolo Veronesi; Mattia Intra; Rosalba Torrisi; Anna Cardillo; Elisabetta Campagnoli; Aron Goldhirsch; Marco Colleoni Journal: Breast Cancer Res Treat Date: 2008-10-07 Impact factor: 4.872
Authors: José Baselga; Patricia Gómez; Richard Greil; Sofia Braga; Miguel A Climent; Andrew M Wardley; Bella Kaufman; Salomon M Stemmer; António Pêgo; Arlene Chan; Jean-Charles Goeminne; Marie-Pascale Graas; M John Kennedy; Eva Maria Ciruelos Gil; Andreas Schneeweiss; Angela Zubel; Jutta Groos; Helena Melezínková; Ahmad Awada Journal: J Clin Oncol Date: 2013-06-03 Impact factor: 44.544