Triple-negative breast cancer (TNBC) is an aggressive disease with a poor prognosis, making it essential to improve the efficacy of neoadjuvant therapy while minimizing treatment-related toxicity. At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Xiaowei Qi and colleagues from Southwest Hospital, Army Medical University presented the latest results from the NeoTAPPL study (Abstract #600).The Phase II study evaluated an anthracycline-free neoadjuvant regimen combining penpulimab, taxane, and carboplatin. The regimen achieved a total pathological complete response (tpCR) rate of 64.1%, while the incidence of Grade ≥3 treatment-related adverse events was only 37.5%, demonstrating a favorable balance between efficacy and safety. These findings provide new clinical evidence supporting anthracycline de-escalation strategies in early-stage TNBC.
Oncology Frontier invited Xiaowei Qi to discuss the study’s findings and their clinical significance.
Study Overview
Background
Triple-negative breast cancer is the most aggressive subtype of breast cancer, characterized by rapid disease progression and poor clinical outcomes. Its high tumor mutational burden and immune-rich tumor microenvironment also make TNBC particularly responsive to immunotherapy.
Landmark studies including IMpassion031 and KEYNOTE-522 established that adding immune checkpoint inhibitors to neoadjuvant chemotherapy significantly improves pathological complete response (pCR). Consequently, neoadjuvant immunotherapy combined with taxane-, platinum-, and anthracycline-based chemotherapy has become a standard treatment option for early-stage TNBC.
However, the KEYNOTE-522 regimen is associated with substantial toxicity, with Grade ≥3 treatment-related adverse events occurring in nearly 78% of patients. Therefore, identifying less toxic regimens without compromising efficacy remains an important clinical objective.
Several previous studies have suggested that anthracyclines may not always be necessary. The NeoSTOP and NeoCART trials demonstrated that taxane-plus-platinum regimens achieved pCR rates comparable to anthracycline-containing regimens while offering improved safety. Similarly, the NeoPACT study reported a pCR rate of 58% using pembrolizumab combined with docetaxel and carboplatin in an anthracycline-free approach.
Unlike most currently available PD-1 inhibitors, which are IgG4 antibodies, penpulimab is an IgG1 PD-1 inhibitor. Before NeoTAPPL, its efficacy, safety, and effects on the tumor microenvironment in neoadjuvant TNBC had not been clinically evaluated.
Study Design
NeoTAPPL is a prospective, multicenter, single-arm Phase II study (ChiCTR2300071925) evaluating the efficacy and safety of penpulimab combined with taxane and carboplatin as neoadjuvant therapy for TNBC.
Eligible patients were women aged 18–75 years with Stage II or III TNBC, an ECOG performance status of 0–1, and no prior systemic therapy for advanced disease.
Patients received:
- Penpulimab 200 mg every 3 weeks for six cycles
- Docetaxel 75 mg/m² or nab-paclitaxel 260 mg/m² every 3 weeks for six cycles
- Carboplatin (AUC 6) every 3 weeks for six cycles
The primary endpoint was total pathological complete response (tpCR; ypT0/Tis ypN0).
Secondary endpoints included breast pCR, axillary pCR, residual cancer burden (RCB), objective response rate (ORR), event-free survival (EFS), invasive disease-free survival (iDFS), overall survival (OS), and safety.
Results
A total of 64 patients completed neoadjuvant treatment and subsequently underwent surgery. The median age was 53 years (range, 32–73), and 84.4% had Stage II disease.
The study reported:
- tpCR: 64.1% (41/64; 95% CI, 51.1%–75.7%)
- RCB 0–1: 78.1% (50/64)
- Objective response rate (ORR): 93.8%
- Disease control rate (DCR): 98.4%
The benefit was consistent across clinically important subgroups. Patients with Stage II disease achieved a pCR rate of 64.9%, while those with Stage III disease achieved 60.0%. Similar results were observed regardless of baseline lymph node status, with pCR rates of 64.9% in node-negative patients and 63.0% in node-positive patients.
Regarding safety, every patient experienced at least one treatment-related adverse event, but Grade ≥3 events occurred in only 37.5% of patients. The most common severe adverse events were alopecia (20.3%), anemia (14.1%), neutropenia (10.9%), and leukopenia (10.9%).
Conclusion
The anthracycline-free combination of penpulimab, taxane, and carboplatin demonstrated encouraging antitumor activity together with a manageable safety profile in patients with early-stage TNBC. Clinical benefit was observed regardless of disease stage or lymph node involvement, supporting this regimen as a promising de-escalation strategy that warrants further investigation.
Investigator Perspective
Xiaowei Qi
Adding immune checkpoint inhibitors to standard neoadjuvant chemotherapy significantly improves pCR rates in TNBC but is also associated with a relatively high incidence of Grade 3 or higher adverse events.
Anthracycline-sparing strategies have shown encouraging efficacy while reducing treatment toxicity, and the NeoTAPPL study further supports this approach.
However, NeoTAPPL is a single-arm Phase II trial, without a direct comparison against the current anthracycline-containing standard regimen. The encouraging 60% pCR rate observed in Stage III patients should therefore be regarded as exploratory and requires confirmation in adequately powered randomized controlled trials.
It is also important to recognize that immune checkpoint inhibitors do not benefit every patient with TNBC. Identifying patients who are less likely to respond and selecting more appropriate treatment strategies remains an important area of ongoing research.
Our research team is conducting further spatial multi-omics translational analyses based on the NeoTAPPL study, with the goal of developing more personalized treatment strategies and ultimately improving survival outcomes for patients with TNBC.
Expert Profile
Xiaowei Qi
Southwest Hospital, Army Medical University
