Adding cetuximab (Erbitux) to cisplatin doubled the overall response rate and appeared to prolong progression-free and overall survival in a randomized phase II study among patients with metastatic triple-negative breast cancer. Although the trial did not meet its primary endpoint of overall response rate, the authors of the study, published in the Journal of Clinical Oncology, concluded that the results warranted further investigation of the combination in treating metastatic triple-negative breast cancer.
Triple-negative breast cancer, defined as estrogen receptor–negative, progesterone receptor–negative, and human epidermal growth factor receptor 2 (HER2)-negative disease, has been shown to overexpress epidermal growth factor receptor (EGFR). In addition, the authors noted that triple-negative breast cancer cell lines that overexpress EGFR are inhibited by the anti-EGFR monoclonal antibody cetuximab, which has also been shown to enhance the antitumor activity of cisplatin and carboplatin.
In this study, patients who had received no more than one previous chemotherapy regimen were randomly assigned on a 2:1 schedule to receive up to six cycles of cisplatin plus cetuximab or cisplatin alone. “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 investigators stated. The study was conducted in Europe, Israel, and Australia.
“The study groups were well balanced for performance status, line of treatment, and median time to metastasis,” the authors noted. Overall, 86% of patients had infiltrating ductal carcinoma and the median age was 52 years.
Study Outcomes
The best overall response rate was 20% (95% confidence interval [CI] = 13–29; 23 of 115) and 10% (95% CI = 4–21; 6 of 58) in the cisplatin plus cetuximab and cisplatin-alone groups, respectively (odds ratio = 2.13; 95% CI = 0.81–5.59; P = .11). “Thus, the primary endpoint was not met,” and the researchers stated, and it was a negative trial.
“However, it is possible that this may not accurately represent the true activity of this combination regimen as, unlike other randomized phase II studies, the primary endpoint was based on two null hypotheses; on the one hand, superiority of the cetuximab arm and, on the other, an [overall response rate] of greater than 20%,” the authors noted. “Therefore, the observed doubling of the overall response rate with the addition of cetuximab to cisplatin should not be ignored when considering the potential of anti-EGFR agents in [metastatic triple-negative breast cancer].”
Median progression-free survival was significantly longer among patients receiving cisplatin plus cetuximab than among patients receiving cisplatin alone (3.7 vs 1.5 months; hazard ratio [HR] = 0.67; 95% CI = 0.47–0.97; P = .032). Median overall survival among patients receiving cisplatin plus cetuximab was 12.9 vs 9.4 months among those receiving cisplatin alone (HR = 0.82; 95% CI = 0.56–1.20; P = .31).
“All 171 patients experienced at least one adverse event,” the researchers reported, with 61% of patients in the cisplatin plus cetuximab group and 42% of the patients in the cisplatin-alone group experiencing at least one grade 3 or 4 adverse event. “The more frequent grade 3 or 4 adverse events in the cisplatin plus cetuximab compared with the cisplatin-alone group are mainly owing to grade 3 acne-like rash associated with cetuximab, which was generally manageable. In addition, patients in the cisplatin plus cetuximab group had a slightly higher incidence of grade 3 or 4 neutropenia than patients in the cisplatin-alone group as well as some grade 3/4 infusion-related reactions.” ■
Baselga J, et al: J Clin Oncol 31:2586-2592, 2013.
