A phase II, randomized, open-labeled study to evaluate low-dose pembrolizumab in addition to neoadjuvant chemotherapy for triple-negative breast cancer (TNBC).

Abstract

Background: Breast cancer is the most common malignancy diagnosed in women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive subtype, accounting for nearly one third of all breast cancers in India. The addition of pembrolizumab to neoadjuvant chemotherapy improved the pathological response and event free survival in patients with TNBC. However, for most patients in low- and middle-income countries, immunotherapy remains inaccessible due to its high cost. Pharmacological and early clinical data suggest that a lower dose of pembrolizumab may be effective. However, there are no prospective clinical trials in patients with TNBC.

Methods: This is a single-site phase II, randomized, open-labeled, parallel-group trial. Eligible patients will be randomized (1:1) to either of the two treatment groups. Patients in the control arm will be administered standard of care chemotherapy [4 cycles of dose-dense doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²), followed by 4 cycles of dose-dense paclitaxel (175 mg/m²)]. Patients in the experimental arm will receive 3 doses of pembrolizumab 50 mg every 6 weeks along with neoadjuvant dose-dense chemotherapy. The primary objective of the study is to compare the pathological complete response with the addition of low-dose pembrolizumab to neoadjuvant chemotherapy in patients with TNBC. Secondary objectives include invasive disease-free survival and quality of life assessment.

Discussion: The PLANeT trial aims to establish the efficacy of low-dose pembrolizumab in addition to neoadjuvant chemotherapy in patients with triple-negative breast cancer patients. This strategy, if found effective, will help improve the outcomes of women with TNBC who currently have limited access to pembrolizumab.

Trial registration: Clinical Trials Registry of India-CTRI/2024/01/062088.