PURPOSE: To evaluate the efficacy and safety of the pan-ErbB receptor tyrosine-kinase inhibitor CI-1033 in metastatic breast cancer (MBC). EXPERIMENTAL DESIGN:Patients with measurable, progressive, or recurrent MBC whose primary tumor expressed > or =1 ErbB receptor were randomized to the following CI-1033 regimens: 50 mg (arm A) or 150 mg (arm B) daily without rest period, or 450 mg/day x 14 days every 21 days (arm C). The primary endpoint was 1-year progression-free survival (PFS). RESULTS: Overall, 194 patients were treated. One-year PFS estimates were 3.8, 2.0, and 4.6%; median PFS was 61, 56, and 58 days; and investigator-assessed overall response rates were 1.5, 1.5, and 7.3%, in arms A, B, and C, respectively. Response duration was 110-419 days. In arm C, response (18.8 vs. 2.6%) and 1-year overall survival rates (86.7 vs. 47.5%) were greater in patients with HER2-positive versus HER2-negative tumors. The incidence of grade 3/4 adverse events (AEs) was dose-dependent, affecting 10.3, 48.6, and 80.4% of patients in arms A, B and C, respectively. The most common grade 3/4, treatment-related AEs were diarrhea, asthenia, and stomatitis. Arm C enrollment was prematurely discontinued due to a high frequency of grade 3/4 AEs. CONCLUSION: Single-agent CI-1033 did not show clinically meaningful activity in heavily pretreated patients with MBC expressing > or =1 ErbB receptor. Antitumor activity was observed in arm C patients with HER2-positive tumors. However, only the 50 mg dose was well tolerated, and the highest dose reached unacceptable levels of toxicity.
RCT Entities:
PURPOSE: To evaluate the efficacy and safety of the pan-ErbB receptor tyrosine-kinase inhibitor CI-1033 in metastatic breast cancer (MBC). EXPERIMENTAL DESIGN:Patients with measurable, progressive, or recurrent MBC whose primary tumor expressed > or =1 ErbB receptor were randomized to the following CI-1033 regimens: 50 mg (arm A) or 150 mg (arm B) daily without rest period, or 450 mg/day x 14 days every 21 days (arm C). The primary endpoint was 1-year progression-free survival (PFS). RESULTS: Overall, 194 patients were treated. One-year PFS estimates were 3.8, 2.0, and 4.6%; median PFS was 61, 56, and 58 days; and investigator-assessed overall response rates were 1.5, 1.5, and 7.3%, in arms A, B, and C, respectively. Response duration was 110-419 days. In arm C, response (18.8 vs. 2.6%) and 1-year overall survival rates (86.7 vs. 47.5%) were greater in patients with HER2-positive versus HER2-negative tumors. The incidence of grade 3/4 adverse events (AEs) was dose-dependent, affecting 10.3, 48.6, and 80.4% of patients in arms A, B and C, respectively. The most common grade 3/4, treatment-related AEs were diarrhea, asthenia, and stomatitis. Arm C enrollment was prematurely discontinued due to a high frequency of grade 3/4 AEs. CONCLUSION: Single-agent CI-1033 did not show clinically meaningful activity in heavily pretreated patients with MBC expressing > or =1 ErbB receptor. Antitumor activity was observed in arm C patients with HER2-positive tumors. However, only the 50 mg dose was well tolerated, and the highest dose reached unacceptable levels of toxicity.
Authors: George Iancu; Dragos Serban; Cristinel Dumitru Badiu; Ciprian Tanasescu; Mihai Silviu Tudosie; Corneliu Tudor; Daniel Ovidiu Costea; Anca Zgura; Raluca Iancu; Danut Vasile Journal: Exp Ther Med Date: 2021-12-03 Impact factor: 2.447
Authors: Greg M Thurber; Thomas Reiner; Katherine S Yang; Rainer H Kohler; Ralph Weissleder Journal: Mol Cancer Ther Date: 2014-02-19 Impact factor: 6.261
Authors: Phillip A Schwartz; Petr Kuzmic; James Solowiej; Simon Bergqvist; Ben Bolanos; Chau Almaden; Asako Nagata; Kevin Ryan; Junli Feng; Deepak Dalvie; John C Kath; Meirong Xu; Revati Wani; Brion William Murray Journal: Proc Natl Acad Sci U S A Date: 2013-12-17 Impact factor: 11.205
Authors: Daphne Gschwantler-Kaulich; Thomas W Grunt; Daniela Muhr; Renate Wagner; Heinz Kölbl; Christian F Singer Journal: PLoS One Date: 2016-01-06 Impact factor: 3.240