MILAN – Targeting the epidermal growth factor receptor with cetuximab increased the overall response rate and time to disease progression in women with metastatic triple-negative breast cancer in the randomized phase II BALI-1 trial.
“This is the first randomized trial suggesting that cetuximab may be a potential addition to the treatment of patients with triple-negative breast cancer, and we believe this study makes a strong argument for studying EGFR targeting in this subgroup of breast cancer patients,” principal investigator Dr. José Baselga said during the Presidential Symposium at the annual congress of the European Society for Medical Oncology.
Eric P. Winer
Cetuximab (Erbitux), a monoclonal antibody targets the epidermal growth factor receptor (EGFR), which is expressed in more than half of triple-negative disease, a difficult to treat subset that accounts for about 15% of all breast cancers but a disproportionate number of deaths.
Among the 173 evaluable patients, the overall response rate by investigator was 10.3% with cisplatin alone vs. 20% with cetuximab plus cisplatin (P = .11).
Progression-free survival more than doubled from a median of 1.5 months with cisplatin alone to 3.7 months with cetuximab plus cisplatin (hazard ratio 0.67, P = .03).
The study did not, however, meet its primary objective of an overall response rate would exceeding 20% in the experimental arm, said Dr. Baselga, chief of the division of hematology/oncology and associate director of the Massachusetts General Hospital Cancer Center, Boston. Although there is no standard treatment for triple-negative breast cancer, there were concerns in the design of the study about the suitability of cisplatin as a comparator, he explained.
Still, Dr. Baselga remained positive about the results, noting that the chance for response was twice as high for patients receiving cetuximab plus cisplatin (odds ratio 2.12).
Overall survival data are not yet available, but will be presented at a later date, he said.
Dr. Eric Winer, who was invited to discuss the findings, said the approach is worthy of pursuit, but that the modest differences between arms could be due to chance or that the unblinded nature of the trial could have affected progression-free survival and the overall response rate.
“The results are consistent with prior studies suggesting some limited activity of cetuximab in patients with triple-negative disease in combination with chemotherapy,” said Dr. Winer, director of the Breast Oncology Center at the Dana-Farber Cancer Institute in Boston.
He suggested that future trials could pair cetuximab with other chemotherapy partners or determine which tumor types benefit from cetuximab. “This regimen is not ready for use outside of a trial,” he said. “There appears to be a small subset that may derive benefit from the addition of cetuximab in additional trials, with extensive correlative, translational trials needed to identify patients more likely to respond.”
Subgroup analyses performed by the BALI-1 investigators found no significant differences in overall response rate with cetuximab plus cisplatin based on age, performance status, menopausal status, or lines of treatment, Dr. Baselga said.
Less than one-third of women in both arms were 60 years of age or older, two-thirds had an ECOG performance status of 0, and 27% had received second-line treatment. The median time from diagnosis to metastasis was short at 15 months, with lung metastases present in 55.7% of the experimental arm and 44.8% in the cisplatin-alone arm.
Centers in 11 countries randomly assigned 58 women to cisplatin 75 mg/m2 IV on day 1 for up to six 3-week cycles and 115 women to the same regimen plus cetuximab 400 mg/m2 for the initial dose then 250 mg/m2 weekly until progressive disease or unacceptable toxicity.
No new safety signals were observed in the study, Dr. Baselga said. Grade 3/4 adverse events that occurred in 5% or more of patients in either the experimental or cisplatin-only arms included neutropenia (9.6% vs. 5.3%), fatigue (8.8% vs. 7%), dyspnea (6.1% vs. 1.8%), and acne-like rash (14% vs. 0%).
Merck KGaA sponsored the study. Dr. Baselga disclosed no relevant conflicts of interest, but two of his coinvestigators are employees of Merck KGaA.