Keynote 522 trial#
Keynote 522 plus#

Keynote 522 trial#

In addition, the KEYNOTE-522 trial showed that adding pembrolizumab was able to improve the pCR rates compared with placebo, improving from 51.2% to 64.8% ( P < 0.001). The I-SPY 2 trial, one of the first to assess neoadjuvant immunotherapy, substantially demonstrated an approximately threefold increase in pCR rates in TNBC patients (22% in patients without pembrolizumab versus 60% in patients with pembrolizumab).

Keynote 522 plus#

However, the results of trials focusing on neoadjuvant ICI plus chemotherapy in patients with TNBC seemed slightly inconstant. In routine clinical practice, chemotherapy combined with PD-1 blockade are commonly given to advanced TNBC patients with PD-L1-positive tumors, because of the positive findings from large phase 3 randomized controlled trials. Therefore, patients with TNBC may benefit more from immune-checkpoint inhibitors (ICIs). Indeed, TNBC is a more immunogenic molecular subtype, containing higher levels of stromal tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) expression, which suggests a greater immunogenic potential.

Patients with TNBC, however, approximately 40%-50% achieved a complete response after NAC, and their subsequent treatment selections are limited. Previous studies have shown that the pathological complete response (pCR) rate for TNBC after neoadjuvant chemotherapy (NAC) has typically been higher than for breast cancer of other molecular subtypes, and there is a marked reduction in recurrences and deaths among patients who achieve a pCR compared with those who have residual lesions after neoadjuvant therapies. There is a poorer prognosis for TNBC patients compared to those with other subtypes of breast cancer, since it exhibits aggressive clinical behavior and lacks adequate molecular targets for therapy. The diagnosis of triple-negative breast cancers (TNBCs) refers to those lacking both estrogen receptors (ER and PR) as well as the human epidermal growth factor receptor 2 (HER2). Compared to clinical trials, however, there was a slightly lower pCR rate in this multicentered real-world study. It is possible to achieve a meaningful pCR rate and DFS by combining neoadjuvant checkpoint blockade with chemotherapy in patients with high-risk TNBC. The most common AEs were nausea (63.4%), fatigue (42.7%), leucopenia (30.0%) and elevated transaminase (11.7%). The DFS of patients with pCR2 and non-pCR2 after neoadjuvant therapy was significantly different (HR = 0.28, 95% CI 0.10–0.79 P = 0.038). 33 patients with non-pCR2 tumors were found to have a median DFS of 20.7 months (95% CI 16.3 months-not reached). ResultsĪmong the patients in the current study, 34.9% of patients were able to achieve pCR1, and 47.6% of patients had achieved pCR2. Secondary endpoints included pCR2 defined as ypT0/Tis, overall response rate (ORR), disease-free survival (DFS), drug-related adverse events (AEs) and biomarkers. PCR1 defined as ypT0/Tis and ypN0 was the primary endpoint. Methodsīetween November 2019 and December 2021, 63 early TNBC patients treated with anti-PD-1 antibodies (pembrolizumab or camrelizumab) or anti-PD-L1 antibody (atezolizumab) in combination with chemotherapy at seven institutions were included. However, there have been no real-world studies reporting on the effectiveness of neoadjuvant checkpoint inhibitors in early TNBC. Despite the poor prognosis of triple-negative breast cancer (TNBC), it has been demonstrated that neoadjuvant immunotherapy in combination with chemotherapy can improve the pathologic complete response (pCR) rate and/or long-term outcome of TNBC.