Real-World Outcomes with the KEYNOTE-522 Regimen in Early-Stage Triple-Negative Breast Cancer

Abstract

Background: This study aimed to determine if the neoadjuvant (NAT) KEYNOTE-522 regimen was associated with higher rates of pathologic complete response (pCR), corresponding to higher rates of breast conservation therapy (BCT) in early-stage triple-negative breast cancer (TNBC) patients.

Patients and methods: Stage II-III TNBC patients diagnosed between 2019 and 2022 who underwent NAT were analyzed retrospectively. NAT with KEYNOTE-522 versus control NAT were compared for rates of BCT, axillary node dissection (ALND), pCR, and survival outcomes. The prevalence of immune-related adverse events (irAE) from chemoimmunotherapy was recorded.

Results: Of 240 patients identified: 86 received KEYNOTE-522 and 154 received control. The frequency of pCR was significantly higher in KEYNOTE versus the control cohort, 59.3% and 33.1%, respectively (p = 0.001). There was no significant difference in the rate of BCT between the control (33.1%) and the KEYNOTE-522 (32.1%) groups (p = 0.47). Rates of ALND were significantly lower with KEYNOTE-522 (25.6%) as compared with control (39.6%); p = 0.03. The rate of development of grade 2 or higher irAEs was 34.9%. At a median follow-up of 2.4 years, there was no difference in survival outcomes. BRCA1 patients had high rates of pCR regardless of treatment group, KEYNOTE-522: 80.0% (4/5) and control: 75% (9/12), (p = 1).

Conclusion: This real-world evidence supports the use of the KEYNOTE-522 regimen in patients with early-stage TNBC given the higher pCR rate and corresponding decrease in the rate of ALND. The majority of patients in both NAT cohorts became BCT eligible, but the rate of BCT did not differ between the two groups.

Keywords: Breast conservation therapy; Immune-related adverse events; Immunotherapy; KEYNOTE-522; Pathologic complete response; Pembrolizumab; Triple-negative breast cancer.

FIG. 1

BCT candidacy and surgical procedures following NAT with KEYNOTE-522 versus control. BCT breast conservation therapy, NAT neoadjuvant therapy, BCT-Dx candidate for breast conservation therapy at the time of diagnosis, BCT-NAT candidate for breast conservation therapy after neoadjuvant therapy, BCT final breast-conservation rate, Bilateral-MX patients who underwent mastectomy with contralateral prophylactic mastectomy, Mx-Recon patients with immediate reconstruction following mastectomy

FIG. 2

Multivariate predictors for type of surgical procedure (BCT versus mastectomy). REF reference, CI confidence interval, OR odds ratio, BMI body mass index, NAT neoadjuvant treatment. Age < 50 years was predictive for choice of surgical procedure (mastectomy) (p = 0.02). All other variables including BMI > 30 kg/m², race, presence of pathogenic mutation, MRI obtained after neoadjuvant therapy and self-palpated mass on initial presentation were not significant predictors for type of surgical procedure

FIG. 3

Reduction in mean tumor size following neoadjuvant treatment with the KEYNOTE-522 regimen versus control. The reduction in lesion size (difference of largest tumor diameter on imaging and the largest diameter on final pathology) was greater in patients following neoadjuvant treatment with the KEYNOTE-522 regimen compared with patients who received the control regimen

FIG. 4

Kaplan–Meier curves of survival for patients according to neoadjuvant treatment type. (a) Overall survival curves. (b) Event-free survival. Blue lines represent the KEYNOTE-522 group. Red lines represent the control group

FIG. 5

Distribution of 42 immune-related adverse events (irAEs) observed in stage II/III TNBC patients treated with the KEYNOTE-522 regimen. All irAEs were ≥ grade 2. IrAE breakdown across organs systems—endocrine: hyper/hypothyroidism (11), adrenal insufficiency (9); musculoskeletal: arthritis (6), myositis (1); skin: rash (3); liver: hepatitis (3); gastrointestinal: colitis (3), gastritis (1); lung: pneumonitis (3); nervous system: myelitis (1); blood: neutropenia (1)