Adding pembrolizumab to neoadjuvant chemotherapy significantly increased the percentage of Asian patients with early triple negative breast cancer (TNBC) demonstrating pathological complete response (pCR) at the time of definitive surgery, according to findings presented at the ESMO Asia Virtual Congress 2020, held from 20 to 22 November 2020.
Rebecca Dent, Head and Senior Consultant, Division of Medical Oncology, National Cancer Centre Singapore, Duke-NUS Medical School in Singapore presented findings on behalf of colleagues from the subgroup of patients enrolled from Asia in the phase III KEYNOTE-522 (NCT03036488) trial.
Overall findings from KEYNOTE-5221 reported in The New England Journal of Medicine demonstrated a significantly increased pCR rate of 64.8% following neoadjuvant treatment comprising pembrolizumab plus chemotherapy compared to 51.2% with placebo plus chemotherapy in patients with early TNBC (p < 0.001).
The study enrolled 1174 patients with previously untreated, non-metastatic, centrally confirmed TNBC (T1c N1-2 or T2-4 N0-2 per American Joint Committee on Cancer, 7th edition).
The Asian subgroup consisted of 215 patients recruited from Korea, Japan, Taiwan and Singapore. Following 2:1 randomisation, 136 patients were administered pembrolizumab at 200 mg every 3 weeks and 79 patient were given placebo; both arms also received 4 cycles of paclitaxel and carboplatin, followed by neoadjuvant treatment with 4 cycles of doxorubicin or epirubicin plus cyclophosphamide. After definitive surgery, patients continued treatment for 9 cycles of pembrolizumab/placebo or until recurrence or unacceptable toxicity (adjuvant phase). In the respective treatment arms, the median age was 46 and 51 years. Patients were stratified by positive versus negative nodal status, tumour size (T1/T2 versus T3/T4), and carboplatin schedule (weekly versus every 3 weeks).
The primary endpoints were pCR, defined as no invasive cancer in the breast and negative nodes (ypT0/Tis ypN0) at the time of definitive surgery and event-free survival (EFS); secondary endpoints included pCR, defined as ypT0 ypN0 and ypT0/Tis and overall survival (OS), as well as all efficacy outcomes in patients with a tumour PD-L1 combined positive score (CPS) ≥1.
The primary and secondary pCR endpoints were met
Among the first 125 randomsied Asian patients the median follow-up was 13.0 months and the pCR rates (ypT0/Tis ypN0; primary endpoint) were 59% (95% confidence interval [CI] 47–70) in 75 patients receiving pembrolizumab compared to 40% (95% CI 26–55) in patients on placebo/chemotherapy, which translated to a 19% difference (95% CI 1–35) between treatments that favoured pembrolizumab.
Consistent results were seen across the secondary pCR definitions. In the ypT0 ypN0 cohort, the pCR rate was 51% with pembrolizumab compared to 30% with placebo and the pCR rates in the ypT0/Tis cohort were 61% versus 42%, respectively.
Improvements in pCR were seen irrespective of PD-L1 CPS score and regardless of definition of pCR used. Benefits were most notable in those patients with node positive disease at study entry with a more than 30% increase in pCR.
Adverse events (AEs) were monitored until 30 days post treatment discontinuation. In the entire safety set of 215 patients, the incidence of grade ≥3 treatment-related AEs was 75% with pembrolizumab and 76% with placebo. No deaths occurred with either treatment.
The authors noted that these findings from the subgroup of Asian patients were consistent with those observed in the overall KEYNOTE-522 study population.
They concluded that pembrolizumab in addition to neoadjuvant chemotherapy provided clinically meaningful improvement in pCR rates in patients from Asia with early TNBC.
They also noted that the safty analysis showed that AEs were consistent with the known safety profiles of each agent.
KEYNOTE-522 was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
- N Engl J Med 2020; 382:810-821. DOI:10.1056/NEJMoa1910549.
1O – Dent R, Cortes J, Pusztai L, et al. KEYNOTE-522 Asian Subgroup: Phase 3 Study of Neoadjuvant Pembrolizumab (Pembro) vs Placebo (Pbo) + Chemotherapy (Chemo) Followed by Adjuvant Pembro vs Pbo for Early Triple-Negative Breast Cancer (TNBC). ESMO Asia Virtual Congress 2020 (20-22 November).