Immunotherapy

The randomized, double blind, phase III KEYNOTE-522 trial (NCT03036488) evaluated the addition of immunotherapy to neoadjuvant chemotherapy for patients with stage II and stage III TNBC.[106][Level of evidence B1] Participants were randomly assigned in a 2:1 ratio to receive neoadjuvant chemotherapy (paclitaxel plus carboplatin, followed by doxorubicin plus cyclophosphamide) with either neoadjuvant and adjuvant pembrolizumab or neoadjuvant and adjuvant placebo. Co-primary end points were pCR rate and EFS. The pCR rate, as reported at the time of the first interim analysis for the first 602 participants (pembrolizumab arm, n = 401; placebo arm, n = 201), favored the pembrolizumab arm.

The randomized, double blind, phase III KEYNOTE-522 trial (NCT03036488) evaluated the addition of immunotherapy to neoadjuvant chemotherapy for patients with stage II and stage III TNBC.[106][Level of evidence B1] Participants were randomly assigned in a 2:1 ratio to receive neoadjuvant chemotherapy (paclitaxel plus carboplatin, followed by doxorubicin plus cyclophosphamide) with either neoadjuvant and adjuvant pembrolizumab or neoadjuvant and adjuvant placebo. Co-primary end points were pCR rate and EFS. The pCR rate, as reported at the time of the first interim analysis for the first 602 participants (pembrolizumab arm, n = 401; placebo arm, n = 201), favored the pembrolizumab arm.

A pCR was observed in 64.8% of patients in the pembrolizumab arm and 51.2% of patients in the placebo arm (estimated treatment difference, 13.6%; 95% CI, 5.4%−21.8%; P < .001). Approximately 80% of tumors were positive for programmed death-ligand 1 (PD-L1), but the benefits of pembrolizumab regarding pCR were observed regardless of PD-L1 status.

The randomized, double blind, phase III KEYNOTE-522 trial (NCT03036488) evaluated the addition of immunotherapy to neoadjuvant chemotherapy for patients with stage II and stage III TNBC.[106][Level of evidence B1] Participants were randomly assigned in a 2:1 ratio to receive neoadjuvant chemotherapy (paclitaxel plus carboplatin, followed by doxorubicin plus cyclophosphamide) with either neoadjuvant and adjuvant pembrolizumab or neoadjuvant and adjuvant placebo. Co-primary end points were pCR rate and EFS. The pCR rate, as reported at the time of the first interim analysis for the first 602 participants (pembrolizumab arm, n = 401; placebo arm, n = 201), favored the pembrolizumab arm.

At the time of the fourth interim analysis, when the median follow-up was 39 months, an improved EFS was observed in patients who received pembrolizumab. The 36-month EFS rate was 84.5% for patients who received pembrolizumab and 76.8% for patients who received placebo. (HR, 0.63; 95% CI, 0.48–0.82; P < .001).[107][Level of evidence B1]

The randomized, double blind, phase III KEYNOTE-522 trial (NCT03036488) evaluated the addition of immunotherapy to neoadjuvant chemotherapy for patients with stage II and stage III TNBC.[106][Level of evidence B1] Participants were randomly assigned in a 2:1 ratio to receive neoadjuvant chemotherapy (paclitaxel plus carboplatin, followed by doxorubicin plus cyclophosphamide) with either neoadjuvant and adjuvant pembrolizumab or neoadjuvant and adjuvant placebo. Co-primary end points were pCR rate and EFS. The pCR rate, as reported at the time of the first interim analysis for the first 602 participants (pembrolizumab arm, n = 401; placebo arm, n = 201), favored the pembrolizumab arm.

EFS data are immature.

The randomized, double blind, phase III KEYNOTE-522 trial (NCT03036488) evaluated the addition of immunotherapy to neoadjuvant chemotherapy for patients with stage II and stage III TNBC.[106][Level of evidence B1] Participants were randomly assigned in a 2:1 ratio to receive neoadjuvant chemotherapy (paclitaxel plus carboplatin, followed by doxorubicin plus cyclophosphamide) with either neoadjuvant and adjuvant pembrolizumab or neoadjuvant and adjuvant placebo. Co-primary end points were pCR rate and EFS. The pCR rate, as reported at the time of the first interim analysis for the first 602 participants (pembrolizumab arm, n = 401; placebo arm, n = 201), favored the pembrolizumab arm.

Grade 3 or higher adverse events occurred in 76.8% of participants in the pembrolizumab arm and 72.2% of participants in the placebo arm. Serious treatment-related adverse events occurred in 32.5% of participants in the pembrolizumab arm and 19.5% of participants in the placebo arm. Grade 3 or higher skin rashes, infusion reactions, and adrenal insufficiency were more frequent in the pembrolizumab arm.