Neoadjuvant anthracycline followed by toripalimab combined with nab-paclitaxel in patients with early triple-negative breast cancer (NeoTENNIS): a single-arm, phase II study

Abstract

Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC.

Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II-III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154).

Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3-67.6) and 41 of 70 (58.6%, 95% CI 46.2-70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1-2).

Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation.

Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

Keywords: De-escalation; Immune checkpoint inhibitor; Induction treatment; Neoadjuvant therapy; Triple-negative breast cancer.

Fig. 1

CONSORT Flow chart of participants. All patients enrolled (n = 70) were included in the efficacy analyses. All patients who had received at least one dose of the study medication (n = 70) were evaluated for safety.

Fig. 2

Subgroup analysis of difference in percentages of patients with a total pathological complete response (ypT0/Tis ypN0). Abbreviations: tpCR, total pathological complete response; CI: confidence interval.

Fig. 3

Comparison of biomarkers and response rates. Comparison of CD8-positive cell proportions before and after four cycles of epirubicin-cyclophosphamide (EC) chemotherapy in (A) 23 patients with paired core needle biopsy specimen, (B) tpCR group, and (C) non-tpCR group. The rates of tpCR (ypT0/is ypN0) and bpCR (ypT0/is) compared by (D) CD8 status, (E) sTILs and (F) Ki-67 level in the NeoTENNIS cohort. Error bars represent 95% CIs. ∗P < 0.05; ∗∗P < 0.01. Abbreviations: ns, not significant. BLIS, basal-like immune-suppressed; IM, immunomodulatory; LAR, luminal androgen receptor; sTlLs, stromal tumor-infiltrating lymphocytes. tpCR, total pathological complete response; bpCR, breast pathological complete response; TNBC, triple-negative breast cancer.