Among different subtypes of breast cancer, triple-negative breast cancer (TNBC) is associated with the least overall survival (OS).¹ The use of immune checkpoint inhibitors, such as programmed death 1 (PD1) or programmed death-ligand 1 (PD-L1), benefits TNBC patients.¹ An interim analysis of a phase 3 trial revealed that administration of pembrolizumab, an immune checkpoint inhibitor, along with neoadjuvant chemotherapy, resulted in a pathological complete response in a significant number of patients with high-risk early TNBC.¹

Patients with stage II or III TNBC experience a high risk of recurrence and death, with 71% and 77% of event-free survival (EFS) and OS, respectively, at 5 years.¹ The immediate benefit of neoadjuvant therapy, the current standard of care, offers an increased EFS and OS, providing a pathological complete response in TNBC patients. Meanwhile, the long-term benefit of neoadjuvant + adjuvant therapy aids in preventing the recurrence of metastatic disease.1 Despite such efforts, there is an elevated risk of disease recurrence and death.1 The use of PD1 or PD-L1 in combination with the neoadjuvant chemotherapy treatment has shown to benefit TNBC patients by decreasing tumor activity.¹

A phase 3 KEYNOTE-522 trial demonstrated the efficacy of pembrolizumab, along with neoadjuvant therapy and compared with neoadjuvant chemotherapy, followed by the administration of adjuvant pembrolizumab or placebo, respectively, in TNBC patients.¹ Patients (N=1,174) with untreated stage II or III TNBC were randomly assigned (2:1) to receive 4 cycles of pembrolizumab (200mg) or placebo every 21 days plus paclitaxel and carboplatin, immediately followed by 4 cycles of pembrolizumab or placebo plus doxorubicin cyclophosphamide or epirubicin–cyclophosphamide.¹ In the post-surgery period, patients received adjuvant pembrolizumab (the pembrolizumab-chemotherapy group) or placebo (the placebochemotherapy group) every 3 weeks lasting up to 9 cycles.¹

The results showed that the estimated 3-year EFS rate was 84.5% (95% CI: 81.7-86.9) in the pembrolizumab-chemotherapy group (n=784), as compared with 76.8% (95% CI: 72.2-80.7) in the placebo-chemotherapy group (n=390) (HR=0.63; 95% CI: 0.48-0.82; p<0.001).1 The pembrolizumab regimen reduced the risk of events or death by 37% (HR=0.63; 95% CI: 0.48-0.82; p<0.001) when compared with the chemotherapy-placebo regimen.¹ Pembrolizumab chemotherapy showed a tolerable safety profile with adverse events being consistent with known profiles of each regimen.¹

The authors stated that a key strength of this trial was the inclusion of a control group of patients who received the standard-of-care platinum, taxane, and anthracycline-containing chemotherapy, which permitted the direct comparison of the pembrolizumabchemotherapy combination with the neoadjuvant chemotherapy regimen that has been associated with high response among patients with early TNBC.¹

To conclude, patients with early TNBC showed significantly prolonged EFS with the novel combination of neoadjuvant pembrolizumab + chemotherapy, followed by adjuvant pembrolizumab after surgery than neoadjuvant chemotherapy alone.¹