Randomized Phase II Study of the Anti–Epidermal Growth Factor Receptor Monoclonal Antibody Cetuximab With Cisplatin Versus Cisplatin Alone in Patients With Metastatic Triple-Negative Breast Cancer

• DOI: 10.1200/jco.2012.46.2408
• Publication Date: 2013-06-04T05:10:59Z
• 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 Goem...; Marie-Pascale Graas; M. John Kennedy; Eva Maria Ciruelo...; Andreas Schneeweiss; Angela Zubel; Jutta Groos; Helena Melezínková; Ahmad Awada
• Keywords: Antineoplastic Combined Chemotherapy Protocols -- administration & dosage -- adverse effects; Adult; Maximum Tolerated Dose; Cetuximab; Breast Neoplasms; Breast Neoplasms -- drug therapy -- metabolism -- mortality -- pathology; Antibodies, Monoclonal, Humanized; Risk Assessment; Antibodies; Disease-Free Survival; Drug Administration Schedule; Dose-Response Relationship; 03 medical and health sciences; 0302 clinical medicine; Monoclonal; Cisplatin -- administration & dosage -- adverse effects; Receptors; Antineoplastic Combined Chemotherapy Protocols; Confidence Intervals; Humans; Neoplasm Invasiveness; Proportional Hazards Models; Aged; Neoplasm Staging; Epidermal Growth Factor -- drug effects -- metabolism; Dose-Response Relationship, Drug; Sciences bio-médicales et agricoles; Middle Aged; Prognosis; Survival Analysis; Humanized -- administration & dosage -- adverse effects; 3. Good health; ErbB Receptors; Neoplasm Invasiveness -- pathology; Treatment Outcome; Progesterone -- drug effects -- metabolism; Multivariate Analysis; Female; Drug; Cisplatin; Estrogen -- drug effects -- metabolism; Receptor

Purpose 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 and Methods 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. Results 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. Conclusion 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.