Immune checkpoint inhibitors and chemotherapy versus chemotherapy for early triple-negative breast cancer.
Triple-negative breast cancer (TNBC), an aggressive subtype lacking oestrogen and progesterone receptors and amplification of HER2 receptors, accounts for 12% to 17% of breast cancers. Adjuvant and neoadjuvant chemotherapy improve survival; however, 30% to 40% of early-stage TNBC cases progress to metastatic disease. Recent evidence suggests that combining immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) with chemotherapy may improve pathological complete response and event-free survival.
To assess the benefits and harms of immune checkpoint inhibitors (PD-1 or PD-L1 inhibitors) plus chemotherapy compared with chemotherapy for people with early TNBC.
We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, the WHO ICTRP, and ClinicalTrials.gov up to 6 November 2024. We also searched the reference lists of identified relevant trials or reviews for potentially eligible studies.
Randomised controlled trials (RCTs) comparing PD-1 or PD-L1 inhibitors plus chemotherapy with chemotherapy alone in participants with early TNBC.
Pairs of review authors independently identified studies for inclusion and performed data extraction and risk of bias assessment. Outcomes were pathological complete response, event-free survival (EFS), overall survival (OS), health-related quality of life (HRQoL), and overall rates of any adverse events and serious adverse events (SAEs). We calculated hazard ratios (HRs) for time-to-event data, risk ratios (RRs), odds ratios (ORs), or risk differences (RDs) for dichotomous outcomes, and mean differences (MDs) for continuous outcomes with corresponding 95% confidence intervals (CIs). We performed random-effects meta-analyses to summarise the evidence and evaluated the certainty of evidence using the GRADE approach.
We included seven RCTs with a total of 4341 participants. Two trials investigated PD-1 inhibitors (i.e. pembrolizumab), and five investigated PD-L1 inhibitors (i.e. durvalumab, atezolizumab) in the intervention group. Six studies used neoadjuvant chemotherapy (NACT), and one study used adjuvant chemotherapy (ACT) in the control group. The studies cover a five-year follow-up period. Two studies were at low risk of bias for all reported outcomes. The main limitation of the other trials was lack of blinding. PD-1 or PD-L1 inhibitors plus chemotherapy versus chemotherapy alone beforebreast cancer surgery PD-1 or PD-L1 inhibitors plus chemotherapy probably increase pathological complete response rate (RR 1.47, 95% CI 1.15 to 1.86; 6 studies, 1564 participants; moderate-certainty evidence); improve EFS (HR 0.64, 95% CI 0.52 to 0.79; 4 studies, 1789 participants; high-certainty evidence); and probably improve OS (HR 0.56, 95% CI 0.34 to 0.93; 3 studies, 1681 participants; moderate-certainty evidence) compared with chemotherapy alone. There may be little or no difference between PD-1 or PD-L1 inhibitors plus chemotherapy and chemotherapy alone in HRQoL (MD -1.49, 95% CI -3.88 to 0.91; 2 studies, 1395 participants; low-certainty evidence). PD-1 or PD-L1 inhibitors plus chemotherapy probably have little or no effect on any adverse events (OR 0.26, 95% CI 0.05 to 1.24; 3 studies, 1781 participants; moderate-certainty evidence) and treatment-related deaths (RD 0.2%, 95% CI -0.4% to 0.8%; 4 studies, 1761 participants; moderate-certainty evidence) compared with chemotherapy alone. PD-1 or PD-L1 inhibitors plus chemotherapy probably increase immune-related SAEs (OR 1.75, 95% CI 1.15 to 2.67; 5 studies, 2016 participants; moderate-certainty evidence) compared with chemotherapy alone. PD-1 or PD-L1 inhibitors plus chemotherapy versus chemotherapy alone afterbreast cancer surgery There may be little or no difference between PD-1 or PD-L1 inhibitors plus chemotherapy and chemotherapy alone in EFS (HR 1.11, 95% CI 0.87 to 1.42; 1 study, 2199 participants; low-certainty evidence), OS (HR 1.23, 95% CI 0.87 to 1.73; 1 study, 2199 participants; low-certainty evidence), HRQoL (MD -1.02, 95% CI -2.71 to 0.67; 1 study, 2168 participants; low-certainty evidence), any adverse events (OR 3.38, 95% CI 0.93 to 12.33; 1 study, 2177 participants; low-certainty evidence), and treatment-related deaths (RD -0.1%, 95% CI -0.4% to 0.2%; 1 study, 2177 participants; low-certainty evidence). PD-1 or PD-L1 inhibitors plus chemotherapy probably increase immune-related SAEs (OR 1.81, 95% CI 1.47 to 2.24; 1 study, 2177 participants; moderate-certainty evidence) compared to chemotherapy alone.
Combining PD-1 or PD-L1 inhibitors with chemotherapy compared to chemotherapy alone before breast cancer surgery improves pathological response, EFS, and OS in early TNBC. In contrast, the combination of PD-1/PD-L1 inhibitors with chemotherapy after breast cancer surgery may have little to no effect on EFS and OS in early-stage TNBC when compared with chemotherapy alone. The addition of PD-1 or PD-L1 inhibitors probably increases immune-related SAEs.
To assess the benefits and harms of immune checkpoint inhibitors (PD-1 or PD-L1 inhibitors) plus chemotherapy compared with chemotherapy for people with early TNBC.
We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, the WHO ICTRP, and ClinicalTrials.gov up to 6 November 2024. We also searched the reference lists of identified relevant trials or reviews for potentially eligible studies.
Randomised controlled trials (RCTs) comparing PD-1 or PD-L1 inhibitors plus chemotherapy with chemotherapy alone in participants with early TNBC.
Pairs of review authors independently identified studies for inclusion and performed data extraction and risk of bias assessment. Outcomes were pathological complete response, event-free survival (EFS), overall survival (OS), health-related quality of life (HRQoL), and overall rates of any adverse events and serious adverse events (SAEs). We calculated hazard ratios (HRs) for time-to-event data, risk ratios (RRs), odds ratios (ORs), or risk differences (RDs) for dichotomous outcomes, and mean differences (MDs) for continuous outcomes with corresponding 95% confidence intervals (CIs). We performed random-effects meta-analyses to summarise the evidence and evaluated the certainty of evidence using the GRADE approach.
We included seven RCTs with a total of 4341 participants. Two trials investigated PD-1 inhibitors (i.e. pembrolizumab), and five investigated PD-L1 inhibitors (i.e. durvalumab, atezolizumab) in the intervention group. Six studies used neoadjuvant chemotherapy (NACT), and one study used adjuvant chemotherapy (ACT) in the control group. The studies cover a five-year follow-up period. Two studies were at low risk of bias for all reported outcomes. The main limitation of the other trials was lack of blinding. PD-1 or PD-L1 inhibitors plus chemotherapy versus chemotherapy alone beforebreast cancer surgery PD-1 or PD-L1 inhibitors plus chemotherapy probably increase pathological complete response rate (RR 1.47, 95% CI 1.15 to 1.86; 6 studies, 1564 participants; moderate-certainty evidence); improve EFS (HR 0.64, 95% CI 0.52 to 0.79; 4 studies, 1789 participants; high-certainty evidence); and probably improve OS (HR 0.56, 95% CI 0.34 to 0.93; 3 studies, 1681 participants; moderate-certainty evidence) compared with chemotherapy alone. There may be little or no difference between PD-1 or PD-L1 inhibitors plus chemotherapy and chemotherapy alone in HRQoL (MD -1.49, 95% CI -3.88 to 0.91; 2 studies, 1395 participants; low-certainty evidence). PD-1 or PD-L1 inhibitors plus chemotherapy probably have little or no effect on any adverse events (OR 0.26, 95% CI 0.05 to 1.24; 3 studies, 1781 participants; moderate-certainty evidence) and treatment-related deaths (RD 0.2%, 95% CI -0.4% to 0.8%; 4 studies, 1761 participants; moderate-certainty evidence) compared with chemotherapy alone. PD-1 or PD-L1 inhibitors plus chemotherapy probably increase immune-related SAEs (OR 1.75, 95% CI 1.15 to 2.67; 5 studies, 2016 participants; moderate-certainty evidence) compared with chemotherapy alone. PD-1 or PD-L1 inhibitors plus chemotherapy versus chemotherapy alone afterbreast cancer surgery There may be little or no difference between PD-1 or PD-L1 inhibitors plus chemotherapy and chemotherapy alone in EFS (HR 1.11, 95% CI 0.87 to 1.42; 1 study, 2199 participants; low-certainty evidence), OS (HR 1.23, 95% CI 0.87 to 1.73; 1 study, 2199 participants; low-certainty evidence), HRQoL (MD -1.02, 95% CI -2.71 to 0.67; 1 study, 2168 participants; low-certainty evidence), any adverse events (OR 3.38, 95% CI 0.93 to 12.33; 1 study, 2177 participants; low-certainty evidence), and treatment-related deaths (RD -0.1%, 95% CI -0.4% to 0.2%; 1 study, 2177 participants; low-certainty evidence). PD-1 or PD-L1 inhibitors plus chemotherapy probably increase immune-related SAEs (OR 1.81, 95% CI 1.47 to 2.24; 1 study, 2177 participants; moderate-certainty evidence) compared to chemotherapy alone.
Combining PD-1 or PD-L1 inhibitors with chemotherapy compared to chemotherapy alone before breast cancer surgery improves pathological response, EFS, and OS in early TNBC. In contrast, the combination of PD-1/PD-L1 inhibitors with chemotherapy after breast cancer surgery may have little to no effect on EFS and OS in early-stage TNBC when compared with chemotherapy alone. The addition of PD-1 or PD-L1 inhibitors probably increases immune-related SAEs.