| General information |
| Database: | DB00984 |
| Objective: | Epidermal growth factor receptor is overexpressed in metastatic triplenegative breast cancers (mTNBCs), an aggressive subtype of breast cancer. Our randomizedphase II study investigated cisplatin with or without cetuximab in this setting |
| Authors: | Baselga J, et al |
| Title: | Randomizedphase II study of the antiepidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triplenegative breast cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2013 |
| PMID: | 23733761 |
| Trial Design |
| Clinical Trial Id: | NCT00463788 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | advanced triplenegative breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | cetuximab with cisplatin |
| Study Type: | Randomizedphase II study |
| Key Patients Feature: | Patients who had received no more than one previous chemotherapy regimen |
| Biomarker: | triplenegative(human epidermal growth factor receptor 2, ER, PR) |
| Biomark Analysis: | NA |
| Control Group Info: | cetuximab with cisplatin versus cisplatin alone |
| Treatment Info: | patients were randomly assigned on a 2:1 schedule to receive no more than six cycles of cisplatin plus cetuximab or cisplatin alone. Patients receiving cisplatin alone could switch to cisplatin plus cetuximab or cetuximab alone on disease progression |
| Primary End Point: | overall response rate (ORR). |
| Secondary End Point: | progression free survival (PFS), overall survival (OS), and safety profiles. |
| Patients Number: | 115 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 20% (95% CI, 13 to 29) with cisplatin plus cetuximab and 10% (95% CI, 4 to 21) with cisplatin alone (odds ratio, 2.13; 95% CI, 0.81 to 5.59; P = .11). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Cisplatin plus cetuximab resulted in longer PFS compared with cisplatin alone (median, 3.7 v 1.5 months; hazard ratio [HR], 0.67; 95% CI, 0.47 to 0.97; P = .032). |
| Median OS A vs. C: | 12.9 versus 9.4 months (HR, 0.82; 95% CI, 0.56 to 1.20; P = .31). |
| Adverse Event(agent arm): | All 171 patients experienced at least one adverse event. Altogether, 69 (61%) of 114 patients in the cisplatin plus cetuximab group and 24 (42%) of 57 patients in the cisplatinalone group experienced at least one grade 3 or 4 adverse event. Grade 3 or 4 adverse events occurring in at least 5% of patients in the cisplatin plus cetuximab or cisplatinalone groups are listed in Table 3and included neutropenia (11 [10%] of 114 v three [5%] of 57), fatigue (10 [9%] of 114 v four [7%] of 57), dyspnea (seven [6%] of 114 v one [2%] of 57), and acnelike rash (17 [15%] of 114 v 0%). In the cisplatin plus cetuximab group, grade 3 or 4 dyspnea was associated with clinical deterioration and disease progression in all patients. Other grade 3/4 adverse events with cisplatin plus cetuximab and cisplatin alone were sepsis (two [2%] of 114 v 0%), hypertension (four [4%] of 114 v 0%), and hypomagnesemia (four [4%] of 114 v one [2%] of 57). Any grade and grade 3 infusionrelated reactions occurred in 15 (13%) of 114 and three (3%) of 114 patients in the cisplatin plus cetuximab group, respectively, and in no patients in the cisplatinalone group. There were no treatmentrelated adverse events leading to death. |
| Conclusions: | While the primary study end point was not met, adding cetuximab to cisplatin doubled the ORR and appeared to prolong PFS and OS, warranting further investigation in mTNBC |