Professor Peter Schmid, FRCP, MD, Ph.D., Professor of Cancer Medicine and Lead of the Centre of Experimental Cancer Medicine at Barts Cancer Institute speaks about the ESMO 2021 Abstract – KEYNOTE-522: PHASE III STUDY OF NEOADJUVANT PEMBROLIZUMAB + CHEMOTHERAPY VS. PLACEBO + CHEMOTHERAPY, FOLLOWED BY ADJUVANT PEMBROLIZUMAB VS. PLACEBO FOR EARLY-STAGE TNBC.
Link to Abstract:
https://www.annalsofoncology.org/article/S0923-7534(19)60363-7/fulltext
Abstract:
Backstory:
In the KEYNOTE-173 and I-SPY 2 trials, neoadjuvant pembro + chemo showed tolerable safety and potential antitumor efficacy in participants (pts) with early TNBC. In patients with early TNBC, KEYNOTE-522 (NCT03036488) is a pbo controlled phase III trial of neoadjuvant pembro + chemo followed by adjuvant pembro.
Methodologies:
Patients with previously untreated, non-metastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC) were randomized 2:1 to pembro 200 mg Q3W or pbo, both of which were given with four cycles of paclitaxel + carboplatin, followed by four cycles of doxorubicin or epirubicin + cyclophosphamide (neoadjuvant phase). Patients were given pembro or pbo for 9 cycles after definitive surgery, or until recurrence or intolerable toxicity (adjuvant phase). Patients were divided into groups according to their nodal status (+ vs. -), tumor size (T1/T2 vs. T3/T4), and carboplatin regimen (Q3W vs QW). pCR, defined as ypT0/Tis ypN0, and event-free survival were the two major goals (EFS). pCR, defined as ypT0 ypN0 and ypT0/Tis, OS, and effectiveness in the PD-L1+ population, were all secondary objectives.
Outcomes:
The average period of follow-up was 15.5 months (range, 2.7-25.0). 390 points were assigned to pembro and 784 to pbo. Pembro + chemo demonstrated a statistically significant improvement in pCR (ypT0/Tis ypN0) compared to pbo + chemo: 64.8 percent (95 percent CI, 59.9-69.5) vs 51.2 percent (95 percent CI, 44.1-58.3), P = 0.00055; findings were comparable for the secondary pCR criteria, ypT0 ypN0 (59.9% v (68.6 percent vs 53.7 percent ). pCR (ypT0/Tis ypN0) was 68.9% versus 54.9 percent in the PD-L1+ group and 45.3 percent vs 30.3 percent in the PD-L1- population for pembro vs pbo. In EFS, adding pembro to chemo and then pembro showed a positive trend (HR 0.63 [95 percent CI, 0.43-0.93]). Treatment-related AE rates of grade 3 or higher were 78.0 percent in the pembro + chemo group and 73.0 percent in the pbo + chemo group across phases (death incidence, 0.4 percent vs 0.3 percent, respectively).
Observations:
In patients with early TNBC, adding pembro to neoadjuvant chemo substantially improved the pCR rate. In EFS, neoadjuvant pembro + chemo followed by adjuvant pembro had a positive tendency. The AEs were in line with each agent’s established safety profile.
Identification of clinical trials
NCT03036488.