In the phase II Neo-N trial reported in The Lancet Oncology, Zdenkowski et al found no apparent advantage of lead-in nivolumab in neoadjuvant therapy comprised of nivolumab/carboplatin/paclitaxel for patients with early triple-negative breast cancer.
Study Details
In the investigator-initiated, noncomparative, open-label trial, 108 patients (modified intention-to-treat population) from sites in Australia, New Zealand, and Italy were randomly assigned between July 2020 and April 2022 to receive either:
- Nivolumab at 240 mg followed 2 weeks later by nivolumab at 360 mg and carboplatin at area under the curve (AUC) = 5 every 3 weeks with concurrent paclitaxel at 80 mg/m² once per week for 12 weeks (nivolumab lead-in group, n = 53)
- Concurrent nivolumab at 360 mg and carboplatin at AUC = 5 every 3 weeks with once-per-week paclitaxel at 80 mg/m² for 12 weeks, then 240 mg of nivolumab 2 weeks later (concurrent group, n = 55).
The primary endpoint was pathological complete response at time of surgery.
Key Findings
Pathologic complete response was observed in 27 of 53 patients (51%, 95% confidence interval [CI] = 39%–63%) in the nivolumab lead-in group and in 30 of 55 (55%, 95% CI = 43%–66%) in the concurrent group.
Treatment-related grade 3 or 4 adverse events occurred in 60% of the lead-in group and 69% of the concurrent group; the most common were decreased neutrophil count (47% vs 53%), anemia (11% vs 19%), and increased alanine aminotransferase (6% vs 6%). Treatment-related serious adverse events occurred in 13% vs 36% of patients. No treatment-related deaths were observed.
The investigators concluded, “While this study did not support the hypothesis that lead-in nivolumab before chemotherapy was associated with a pathological complete response advantage, high pathological complete response rates were reached, supporting shorter-duration, non-anthracycline regimens in patients with newly diagnosed triple-negative breast cancer. Future trials are warranted to compare this regimen with the current standards of care.”
Sherene Loi, MD, PhD, of Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Breast Cancer Trials and Bristol Myers Squibb. For full disclosures of the study authors, visit thelancet.com.
