| Abstract: |
Epidermal growth factor receptor is overexpressed in metastatic triple-negative breast cancers (mTNBCs), an aggressive subtype of breast cancer. Our randomized phase II study investigated cisplatin with or without cetuximab in this setting. Patients who had received no more than one previous chemotherapy regimen 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. The primary end point was overall response rate (ORR). Secondary end points studied included progression-free survival (PFS), overall survival (OS), and safety profiles. Analyses included a significance level of α = .10 with no adjustments for multiplicity. The full analysis set comprised 115 patients receiving cisplatin plus cetuximab and 58 receiving cisplatin alone; 31 patients whose disease progressed on cisplatin alone switched to cetuximab-containing therapy. The ORR was 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). 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). Corresponding median OS was 12.9 versus 9.4 months (HR, 0.82; 95% CI, 0.56 to 1.20; P = .31). Common grade 3/4 adverse events included acne-like rash, neutropenia, and fatigue. 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. |
| Keywords: |
survival; adult; controlled study; treatment outcome; aged; disease-free survival; middle aged; survival analysis; mortality; cisplatin; dose response; comparative study; disease free survival; cancer staging; antineoplastic agent; neoplasm staging; metabolism; controlled clinical trial; phase 2 clinical trial; randomized controlled trial; antineoplastic combined chemotherapy protocols; proportional hazards models; drug administration schedule; epidermal growth factor receptor; receptor, epidermal growth factor; drug effect; pathology; dose-response relationship, drug; breast neoplasms; cetuximab; risk assessment; monoclonal antibody; confidence interval; confidence intervals; proportional hazards model; multicenter study; breast tumor; receptors, estrogen; receptors, progesterone; multivariate analysis; neoplasm invasiveness; maximum tolerated dose; drug administration; estrogen receptor; progesterone receptor; tumor invasion; antibodies, monoclonal, humanized
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