Heather McArthur, MD
Clinical Director of Breast Oncology and Komen Distinguished Chair in Clinical Breast Cancer Research
University of Texas Southwestern Medical Center
Dallas, Texas, United States
Disclosure: AstraZeneca (Individual(s) Involved: Self): Advisor or Review Panel member, Consultant, Research Grant or Support; Bristol-Myers Squibb (Individual(s) Involved: Self): Research Grant or Support; Eli Lilly & Company (Individual(s) Involved: Self): Consultant; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support; Puma (Individual(s) Involved: Self): Advisor or Review Panel member; Seattle Genetics (Individual(s) Involved: Self): Advisor or Review Panel member
KEYNOTE-522 (NCT03036488) is a phase 3 study of neoadjuvant pembro + chemo vs placebo + chemo, followed by adjuvant pembro vs placebo in patients (pts) with early-stage TNBC. The primary analysis showed a statistically significant and clinically meaningful improvement in event-free survival (EFS) with pembro + chemo followed by pembro. To assess the robustness and consistency of the primary EFS result, prespecified sensitivity and subgroup analyses for EFS were performed.
Methods: Pts 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/placebo + 4 cycles of paclitaxel/carboplatin, then with 4 cycles of doxorubicin/epirubicin + cyclophosphamide (neoadjuvant phase). After definitive surgery pts received pembro/placebo for 9 cycles or until recurrence or unacceptable toxicity (adjuvant phase). Patients were stratified by nodal status (positive or negative), tumor size (T1/T2 or T3/T4), and carboplatin schedule (Q3W or QW). Dual primary endpoints are pCR rate and EFS. Five prespecified sensitivity analyses for EFS were performed; 2 that assessed impact of different censoring rules and 3 that assessed impact of different event definitions. Treatment effects on EFS were examined in prespecified pt subgroups defined by nodal involvement (positive/negative), disease stage (II/III), menopausal status (pre-menopausal/post-menopausal), HER2 status (2+ by IHC but FISH- or 0-1+ by IHC), and LDH ( >ULN or ≤ULN).
Results: Of 1174 pts randomized, 784 were randomized to pembro + chemo and 390 to placebo + chemo. Median follow-up was 39.1 mo at the March 23, 2021 data cutoff. The benefit of neoadjuvant pembro + chemo followed by adjuvant pembro vs neoadjuvant chemo alone was generally consistent with the primary EFS results for all 5 sensitivity analyses and in each subgroup evaluated (Table).
Conclusions: EFS sensitivity analyses show a robust treatment benefit of neoadjuvant pembro + chemo followed by adjuvant pembro for previously untreated non-metastatic TNBC. This benefit was generally consistent across a broad selection of pt subgroups.