Editor’s Note: At the 2025 ASCO Annual Meeting, multiple cutting-edge oncology studies were presented. Among them were two studies led by Professor Biyun Wang from Fudan University Shanghai Cancer Center. One was a prospective, single-arm phase II clinical trial (Abstract #1101) evaluating the efficacy and safety of camrelizumab in combination with albumin-bound paclitaxel and cisplatin (the AP regimen) as a first-line treatment for metastatic triple-negative breast cancer (mTNBC). Results showed a median PFS of 11.8 months and median OS of 27.1 months, with manageable toxicity. The second study, an ongoing trial (Abstract #TPS1122), aims to predict treatment response to T-DXd in HER2-positive breast cancer brain metastases using68Ga-FAPI PET-CT to assess tumor metabolic heterogeneity. The trial is actively recruiting patients.This article specifically introduces two studies.Study Overview
Abstract 1101 – A Phase II Study of Camrelizumab Plus Albumin-Bound Paclitaxel and Cisplatin as First-Line Therapy for Metastatic Triple-Negative Breast Cancer
Background Platinum-based chemotherapy is a key component in the treatment of triple-negative breast cancer. A previous phase III randomized controlled trial led by the same team had confirmed the superiority of the albumin-bound paclitaxel/cisplatin (AP) regimen in the first-line setting for mTNBC (Wang B, et al. Nat Commun, 2022, 13(1): 4025). Camrelizumab is a humanized anti–PD-1 monoclonal antibody. This prospective, open-label, single-arm phase II trial (NCT04537286) aimed to evaluate the efficacy and safety of camrelizumab combined with the AP regimen in the first-line treatment of mTNBC.
Study Design
Patients with untreated mTNBC received camrelizumab (200 mg D1), nab-paclitaxel (125 mg/m2 D1,D8) and cisplatin (75 mg/m2 D1) intravenously every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR),overall survival (OS) and safety. Exploratory analyses included immunohistochemistry and RNA sequencing of archival tumour samples.
Results A total of 90 patients were enrolled. The median age was 51 years. Nearly half (46.7%) had three or more metastatic sites, and 78.9% had visceral metastases. Most patients (82.2%) had prior exposure to taxane-based therapies.
As of the data cutoff on July 10, 2024, the median follow-up was 18.1 months. The median PFS was 11.8 months (95% CI: 10.1–13.6), and the median OS was 27.1 months (95% CI: 22.1–33.6). The ORR was 71.1%, and the DCR was 86.7%. The median time to response was 1.5 months.
All patients experienced treatment-related adverse events (TRAEs), with grade 3–4 TRAEs occurring in 55.6% of patients. The most common were neutropenia (34.4%), leukopenia (24.4%), and anemia (10.0%). Immune-related adverse events (irAEs) occurred in 57.8% of patients, with the most frequent being reactive cutaneous capillary endothelial proliferation (RCCEP, 45.5%), rash (11.1%), and pneumonitis (10.0%). Grade 3–4 irAEs were rare, occurring in only 4.4% of patients.
Exploratory analyses revealed that patients with PD-L1 combined positive score (CPS) ≥10 had significantly longer PFS (13.7 vs. 11.4 months, P = 0.039). Those with high tumor-infiltrating lymphocytes (TILs) had significantly longer OS (23.1 vs. 10.3 months, P = 0.003). Among patients with basal-like subtype tumors, 81.8% were PD-L1 positive (CPS ≥1), compared to 0% in non-basal subtypes (P= 0.023).
Landmark analysis at three months showed that patients who experienced irAEs during treatment had significantly longer median OS than those who did not (29.3 vs. 22.1 months, P = 0.018).
Pathway analysis revealed that activation of DNA repair pathways (hazard ratio [HR]: 11.6; 95% CI: 2.4–55.7; P = 0.002) and MYC target pathways (HR: 7.4; 95% CI: 1.9–28.2; P = 0.004) were significantly associated with shorter PFS. Activation of the KRAS signaling pathway (HR: 3.2; 95% CI: 1.1–9.7; P = 0.035) was significantly associated with worse OS.
Conclusion Camrelizumab combined with the AP regimen as a first-line treatment for mTNBC showed promising efficacy and manageable toxicity. A randomized controlled trial is warranted to further confirm these findings.
Abstract TPS1122 – A Phase II Study Evaluating ⁶⁸Ga-FAPI PET Uptake Heterogeneity as a Predictive Biomarker for T-DXd Efficacy in HER2-Positive Breast Cancer Brain Metastases
Background Breast cancer is a leading cause of metastasis to the central nervous system (CNS). Approximately 30% of patients with HER2-positive breast cancer develop brain metastases, which are associated with a poor prognosis and limited treatment options. T-DXd has shown promise in treating brain metastases from HER2-positive breast cancer. However, up to 10% patients showed brain metastasis progression at the initial evaluation of treatment and may require radiotherapy or neurosurgery immediately. Identifying predictors of treatment response and determining the timing for local therapy intervention is crucial for personalized medicine.
Heterogeneity in tumor metabolism, as assessed by (68Ga)–labeled fibroblast-activation protein inhibitor (68Ga-FAPI) PET-CT which displays the activity of cancer-associated fibroblasts (CAFs) in the tumor microenvironment, with good sensitivity and specificity in brain metastasis imaging, may serve as a biomarker for treatment response. This study aims to investigate the predictive value of 68Ga-FAPI PET uptake heterogeneity for T-DXd treatment response in HER2-positive breast cancer brain metastases.
Study Design This is an open-label, single-center, phase II clinical trial exploring the heterogeneity of brain metastases in HER2-positive metastatic breast cancer (MBC) and comparing differences in uptake between stable and active brain lesions using ⁶⁸Ga-FAPI PET-CT.
Eligible patients must have HER2-positive MBC with MRI-confirmed brain metastases, including at least one measurable intracranial lesion (≥1.0 cm) that has not been previously treated with radiotherapy. A minimum 4-week interval is required between any prior radiotherapy or neurosurgery and study enrollment. All participants will receive T-DXd and undergo ⁶⁸Ga-FAPI PET-CT scans at baseline and after two cycles of treatment.
The primary endpoint is the difference in baseline heterogeneity index, as measured by ⁶⁸Ga-FAPI PET-CT, between brain lesions that respond to treatment (achieve objective response) and those that do not.
Secondary endpoints include: – Changes in SUVmax and SUVmean from baseline to post-treatment – Differences in baseline heterogeneity index with respect to progression-free survival (PFS), clinical benefit rate (CBR), and overall survival (OS) – Differences in heterogeneity index, SUVmax, and SUVmean between active and stable brain metastases at baseline – Changes in heterogeneity index, SUVmax, and SUVmean of extracranial metastases before and after two treatment cycles
The study aims to enroll 50 patients and is currently recruiting.
Expert Commentary
Professor Biyun Wang: At present, the field of breast cancer treatment is confronted with numerous challenges. Platinum-based chemotherapy plays a critical role in the management of metastatic triple-negative breast cancer (mTNBC). Our previous phase III randomized controlled trial confirmed the superiority of the albumin-bound paclitaxel plus cisplatin (AP) regimen as a first-line treatment for mTNBC.
With the breakthroughs in immunotherapy, chemo-immunotherapy combinations have become the standard of care for patients with PD-L1–positive mTNBC. Both albumin-bound paclitaxel and cisplatin have been shown to exert synergistic effects with immune checkpoint inhibitors. On this basis, our team conducted a prospective, single-arm phase II clinical trial to explore the efficacy and safety of camrelizumab combined with the AP regimen as a first-line treatment for mTNBC. The results were encouraging, with a median progression-free survival (PFS) of 11.8 months and a median overall survival (OS) of 27.1 months, alongside manageable toxicity. These findings may offer a new therapeutic option for patients with mTNBC.
In the treatment of brain metastases from HER2-positive breast cancer, T-DXd has shown promise. However, up to 10% of patients experience intracranial progression at the first response assessment. To address this, our team launched a single-center phase II clinical trial designed to evaluate tumor metabolic heterogeneity using 68Ga-FAPI PET-CT, with the goal of predicting treatment response to T-DXd in HER2-positive breast cancer brain metastases. The study also aims to analyze the differences between stable and active brain lesions. A total of 50 patients are expected to be enrolled, and recruitment is currently underway. We hope this research will help provide more precise and effective therapeutic strategies for patients with HER2-positive breast cancer brain metastases, ultimately advancing the field of breast cancer treatment.
