Discussion
death, tumor, HR-low tumors, breast cancer, toxicity, cancer, triple-negative tumors, TNBC, tumors, TNBCBreast cancer
TUMOR, BREAST CANCER, ADVERSE EVENTS, CANCER, RESIDUAL DISEASE, HAND PRESENTATION, TUMORS
In this single-arm phase II trial, neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin achieved a pCR rate of 64.1% in patients with early TNBC. Treatment-related adverse events of grade 3 or 4 occurred in 76.9% of patients. No grade 5 treatment-related adverse events occurred. Our study meets the primary endpoint showing promising anti-tumor activity with a manageable safety profile of neoadjuvant camrelizumab plus chemotherapy in patients with early TNBC.ICIs combination strategies, including chemoimmunotherapy, have been increasingly investigated in breast cancer, given the promising anti-tumor activity of ICIs monotherapy in a limited subset of patients. Chemotherapy may induce immunogenic cell death, promote antigen release and presentation, and selectively inhibit or deplete immunosuppressive cells to stimulate anticancer immunityThe pCR benefit observed in this study was generally consistent with that of neoadjuvant pembrolizumab plus platinum-containing chemotherapy reported in the KEYNOTE-522 (64.8%) trialOne thing worth noting is that a 10% cut-off was used in this study to define ER/PR negativity, that is, patients with hormone receptor (HR)-low tumors (1% ≤ ER/PR < 10%) that do not formally meet the criteria of ‘triple negative’ (ER and PgR < 1%, HER2-negative) were also enrolled. These HR-low tumors are known to be biologically and clinically similar to TNBC in terms of pCR and survival outcomes and have long been proposed to be redefined as TNBCBreast cancer has historically been considered a non-immunogenic cancer. However, increasing evidence showed PD-L1 expression, particularly in ER-negative subtypes (such as TNBC or HER2-positive ones), suggesting a potential therapeutic opportunity for anti-PD-1/PD-L1 inhibitorsThe safety profile of neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin was generally consistent with those of neoadjuvant nab-paclitaxel and epirubicin in early TNBC patientsThe addition of camrelizumab did not deteriorate chemotherapy-related toxicity. The immune-related adverse events occurred in almost 62% of patients; most were grade 1 or 2. Interestingly, five of the seven patients who discontinued treatment due to adverse events achieved a pCR after four or five cycles of neoadjuvant therapy. The standard neoadjuvant chemotherapy with at least four cycles was previously found to be significantly associated with favorable survival outcomes in breast cancer patients, especially in those with HER2 positive and TNBCIn this study, we added immunotherapy to a combination chemotherapy regimen, and the results showed promising efficacy. Another advantage of this study is that patients with HR-low tumors that are biologically and clinically similar to triple-negative tumors but do not formally meet the ‘triple negative’ criteria are enrolled. Some limitations must be acknowledged. This is a single-arm study with a small sample size. Nevertheless, we used the two-stage design and get statistically significant results. Besides, correlative studies of stromal tumor-infiltrating lymphocytes and tumor mutational burden were not performed in this study. Additionally, the assessment of long-term survival data and safety profiles is crucial when evaluating a potentially curative treatment. The contribution of adjuvant therapy with ICIs to treatment efficacy remains to be established, as well as the optimal treatment to be offered in cases of residual disease. Follow-up and subsequent analyses to assess overall survival and long-term safety are ongoing.To sum up, this trial meets the prespecified endpoints showing showed promising anti-tumor activity and manageable safety of camrelizumab plus neoadjuvant nab-paclitaxel and epirubicin chemotherapy in patients with early TNBC, without compromising the surgery. The long-term survival outcomes are still pending.