Administration of ANTI-PD1 antibody pembrolizumab improves EFS in tnbc patients

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

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