Triple-negative breast cancer (TNBC) remains a challenging subtype to treat due to its aggressive nature and lack of targeted receptors. Recent studies, however, have shown promising results with the use of camrelizumab and apatinib in neoadjuvant settings, potentially improving outcomes for patients with early or locally advanced TNBC. These findings highlight the evolving treatment landscape and the importance of exploring novel therapeutic combinations.
Camrelizumab Plus Chemotherapy Improves pCR Rates
The phase 3 CamRelief study (NCT04613674) evaluated the addition of camrelizumab, an anti-PD-1 antibody, to intensive chemotherapy in patients with early or locally advanced TNBC. The results, presented at the 2024 San Antonio Breast Cancer Symposium and published in JAMA, demonstrated a significant improvement in pathologic complete response (pCR) rates with the camrelizumab regimen.
In all patients, the camrelizumab arm (n = 222) achieved a pCR rate of 56.8% compared to 44.7% in the chemotherapy-alone arm (n = 219), representing a 12.2% difference (95% CI, 3.3%-21.2%; 1-sided P = .0038). This benefit was generally consistent across subgroups, including those with stage III disease and node-positive disease. Specifically, patients with stage III disease treated with camrelizumab plus chemotherapy (n = 79) had a pCR rate of 49.4% versus 38.0% with chemotherapy alone (n = 79), an 11.4% difference (95% CI, –4.0% to 26.8%).
Early trends in event-free survival (EFS), disease-free survival (DFS), and distant disease–free survival also favored the camrelizumab plus chemotherapy arm. According to Dr. Zhi-Ming Shao from Fudan University Shanghai Cancer Center, these data support camrelizumab plus chemotherapy as a potential new neoadjuvant therapeutic option for treating early or locally advanced TNBC.
Apatinib, Sintilimab, and Chemotherapy Combination Shows High pCR Rate
Another study, the phase 2 NeoSAC trial, explored the efficacy and safety of adding apatinib, a VEGFR2 tyrosine kinase inhibitor, to sintilimab (an anti–programmed death 1 antibody) plus carboplatin-taxane based chemotherapy in patients with early TNBC. The trial enrolled 34 patients across three institutions in China. The results showed a pCR rate of 70.6% (95% CI, 53.0-85.3) in the intention-to-treat population.
Subgroup analyses indicated higher pCR rates in patients with stage II disease compared to stage III (77.3% vs 58.3%), age ≤ 50 years versus > 50 years (77.8% vs 62.5%), nodal-negative versus nodal-positive (75.0% vs 68.2%), and stromal tumor-infiltrating lymphocytes (sTILs) ≥ 30% versus sTILs < 30% (83.3% vs 67.9%).
The 36-month disease-free survival (DFS) rate was 94.1%. RNA sequencing results showed that higher ImmuneScore, interferon-related pathway enrichment, and oxeiptosis scores correlated with pCR. The study's authors concluded that the addition of apatinib to sintilimab and carboplatin-taxane-based neoadjuvant chemotherapy demonstrated promising clinical activity and a manageable safety profile in early TNBC.
Safety and Tolerability
In the CamRelief study, the safety profile of camrelizumab plus chemotherapy was manageable and consistent with the known profiles of each agent. However, grade 3 or higher treatment-related adverse events were more frequent in the camrelizumab arm (89.2% vs 83.1%), as were serious adverse events (34.7% vs 22.8%).
Similarly, the NeoSAC trial reported that all patients experienced at least one treatment-related adverse event. The most common grade 3–4 adverse events included leukopenia (47%), neutropenia (36%), and thrombocytopenia (24%).
Implications for Clinical Practice
These studies suggest that both camrelizumab and apatinib, when combined with chemotherapy, can significantly improve outcomes in patients with early or locally advanced TNBC. The higher pCR rates observed in these trials could translate to improved long-term survival for these patients. However, further research is needed to confirm these findings and to identify the patients who are most likely to benefit from these treatments.
The results from the NeoSAC trial also highlight the importance of considering biomarkers, such as ImmuneScore and sTILs, in predicting treatment response. These biomarkers could help clinicians personalize treatment strategies and optimize outcomes for patients with TNBC.
