Low-dose immune checkpoint inhibitors have shown promise in improving outcomes in various cancers. However, the effect of adding low-dose pembrolizumab (LDPm) to neoadjuvant chemotherapy (NACT), the standard of care for triple-negative breast cancer (TNBC), on efficacy outcomes remains uncertain. The PLANeT trial was a phase 2, open-label, randomized controlled trial that evaluated the efficacy of LDPm combined with NACT in patients with untreated stage II to III TNBC without access to standard-dose pembrolizumab (SDPm). The study was conducted at a tertiary cancer center in New Delhi, India. Patients were randomized 1:1 to receive dose-dense NACT (doxorubicin/cyclophosphamide followed by paclitaxel) with or without LDPm (50 mg every 6 weeks for 3 cycles). The primary endpoints were pathological complete response (pCR) rates.

Between February 2024 and February 2025, 157 patients were randomized to receive NACT with (n=78) or without LDPm (n=79). In the intention-to-treat population, the pCR rate was 53.8% (90% confidence interval [CI], 43.9%-63.5%) in the LDPm arm compared with 40.5% (90% CI, 31.1%-50.4%) in the control arm, resulting in an absolute difference of 13.3% (90% CI, 0.3%-26.3%; 1-sided P=.047). In patients who underwent surgery, pCR rates were 56.8% (90% CI, 46.5%-66.6%) in the LDPm arm, versus 41.6% (90% CI, 32.0%-51.6%) in the control arm, representing an absolute difference of 15.2% (90% CI, 2.0%-28.4%; 1-sided P=0.031). In the subgroup analysis, consistent pCR benefits were observed across age, tumor site, nodal status, and HER2 status. Notably, the pCR rate in T3-T4 tumors nearly doubled, from 25% with the chemotherapy-alone group to 46.5% with the LDPm group. The addition of LDPm to chemotherapy improved the residual cancer burden 0/1 rate to 71.6% (90% CI, 61.8%-80.1%) compared with 61.0% (90% CI, 51.0%-70.4%) with chemotherapy alone, resulting in an absolute difference of 10.6% (90% CI, –1.9% to – 23.1%). Safety outcomes revealed a lower incidence of grade 3 or higher adverse events in the LDPm arm (50%) compared with the control arm (59.5%), though 1 treatment-related death occurred in the LDPm arm due to toxic epidermal necrolysis.

The study concluded that LDPm combined with NACT demonstrated a clinically meaningful improvement in pCR rates, comparable with those observed with SDPm in the KN522 trial. Given its efficacy and safety profile, LDPm may serve as a viable treatment alternative in resource-limited settings, providing hope for improved outcomes in patients with TNBC.

Source: Batra A, Bakhshi S, Kumar A, et al. Low-dose pembrolizumab in addition to neoadjuvant anthracycline and taxane in triple-negative breast cancer: a randomized controlled trial. Presented at: ESMO Congress 2025. October 17, 2025; Munich, Germany. Abstract LBA15.