Adjuvant platinum-based chemotherapy fails to improve outcomes in breast cancer subset
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Platinum-based chemotherapy after neoadjuvant chemotherapy did not improve outcomes compared with capecitabine among patients with basal subtype triple-negative breast cancer and residual invasive disease, according to study results.
In addition, the results — published in Journal of Clinical Oncology — showed more severe toxicities occurred with platinum agents than with capecitabine.
“Patients with triple-negative breast cancer and residual invasive disease after completion of neoadjuvant chemotherapy have a high risk for recurrence, which is reduced by adjuvant capecitabine,” Ingrid A. Mayer, MD, MSCI, researcher at Vanderbilt University Medical Center, and colleagues wrote. “Preclinical models support the use of platinum agents in the triple-negative breast cancer basal subtype.”
The randomized phase 3 EA1131 trial included 410 patients with clinical stage II or stage III triple-negative breast cancer and at least 1 cm residual disease after neoadjuvant therapy. The primary analysis included 308 patients (median age, 52 years; 71.1% white; 19.1% Black; 3.2% Asian) with basal subtype disease who received either platinum-based carboplatin or cisplatin (n = 148) once every 3 weeks for four cycles or capecitabine (n = 160) for 14 out of 21 days every 3 weeks for six cycles.
Investigators chose a noninferiority study design with superiority alternative assuming a 4-year invasive DFS rate of 67% with capecitabine. Invasive DFS in patients with basal subtype triple-negative breast cancer served as the primary endpoint.
Median follow-up was 20 months, after which 120 invasive DFS events occurred among patients with basal subtype disease.
Results showed a 3-year invasive DFS rate of 42% (95% CI, 30-53) with platinum-based chemotherapy vs. 49% (95% CI, 39-59) with capecitabine.
Overall, researchers observed 93 distant recurrences, 15 locoregional recurrences, five invasive second primary cancers without recurrence and seven deaths without recurrence or a second primary cancer.
In addition, grade 3 to grade 4 toxicities, mainly anemia and leukopenia, occurred more often with platinum-based chemotherapy vs. capecitabine (26% vs. 15%). The trial was stopped early at the recommendation of the Data and Safety Monitoring Committee because it appeared unlikely that further follow-up would show noninferiority or superiority of platinum-based chemotherapy.
“Participants had a lower-than-expected 3-year invasive DFS regardless of study treatment, highlighting the need for better therapies in this high-risk population,” the researchers wrote. “These findings should discourage the adjuvant use of platinum agents in patients with residual triple-negative breast cancer after neoadjuvant chemotherapy outside of a trial. For now, the use of adjuvant platinum agents in unselected patients with triple-negative breast cancer remains investigational and capecitabine remains the standard therapy.”
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