Neoadjuvant ICIs May Improve Efficacy Outcomes in Early-Stage TNBC

Presurgical immunothearpy improved efficacy outcomes in early-stage triple-negative breast cancer (TNBC) and PD-L1-positive/ERBB2-negative tumors.

Neoadjuvant immune checkpoint inhibitor (ICI) therapy improved efficacy outcomes in early-stage triple-negative breast cancer (TNBC) and PD-L1-positive/ERBB2-negative tumors with manageable adverse events, according to findings from a systematic review and meta-analysis published in JAMA Oncology.

Results also demonstrated that adjuvant ICIs did not produce a benefit in these patients.

“Given the financial and toxicity costs associated with ICIs, future research should prioritize identifying patients most likely to benefit from the addition of ICIs to neoadjuvant chemotherapy,” the study authors wrote. “Moreover, considering our findings, it is crucial to investigate whether adjuvant therapy could be safely omitted, potentially redefining treatment paradigms in [early breast cancer].

Among 9 randomized clinical trials (RCTs) included in this review, 5114 patients met the inclusion criteria, including 2097 patients with TNBC, 1924 with HR-positive/ERBB2-negative tumors, and 1115 with ERBB2-positive tumors.

The addition of ICIs in patients with TNBC was associated with an improved pathologic complete response (pCR) rate regardless of PD-L1 status (absolute improvement, > 10%). Adding ICIs in patients with HR-positive/ERBB2-negative tumors was linked with improved pCR in the PD-L1-positive population (absolute improvement, > 12.2%); however, no such association was noted in ERBB2-positive tumors.

Patients with TNBC who achieved a pCR with the addition of ICIs had improved event-free survival (EFS)(HR = 0.65; 95% CI, 0.42-1.00). This resulted in a 5-year EFS of 92.0% in patients treated with ICIs compared with 88.0% in those who did not receive ICIs. The administration of ICIs in patients with residual disease showed better EFS(HR = 0.77; 95% CI, 0.61-0.98), producing a 5-year EFS of 63.3% with ICIs vs 56.1% without them. Numerical improvements were not shown with adjuvant ICI in patients with either pCR or residual disease, with HRs greater than 1.

“Importantly, the findings presented in this meta-analysis show that neoadjuvant ICI is not only associated with enhanced pCR rates but also extends its impact beyond pCR,” study authors wrote. “Among patients with and without pCR at surgery, patients who had received neoadjuvant ICI therapy had better survival outcomes independent of the administration of adjuvant ICI therapy.”

Grade 3 or greater immune-related adverse events occurred in 10.3% of patients treated with neoadjuvant ICI.

“Adding ICIs to neoadjuvant chemotherapy for [early breast cancer] did not significantly amplify traditional chemotherapy-associated AEs, such as gastrointestinal symptoms or hematologic complications,” the study authors wrote. “However, [immune-related] AEs are noteworthy, with 10.3% being severe in patients receiving ICI therapy. These serious [immune-related] AEs can affect various organs, highlighting the need for careful monitoring when using ICIs in early treatments.”

For this systematic review and meta-analysis, researchers analyzed data from randomized clinical trials that assessed neoadjuvant and adjuvant ICI plus chemotherapy in patients with early breast cancer.

The PubMed database was used to identify all eligible published studies on December 10, 2023. The systematic review identified randomized clinical trials comparing the combination of anti-PD1 and PD-L1 ICI therapy plus chemotherapy vs chemotherapy alone in the neoadjuvant setting in patients with early breast cancer.

“The analysis is focused on clarifying the clinical implications and addressing contentious issues related to the use of anti-PD1/PD-L1 drugs,” the study authors wrote. “This includes unanswered questions such as the benefit of ICI beyond pCR status, the utility of adjuvant ICI therapy, and the role of PD-L1 as a prognostic and predictive biomarker for efficacy outcomes.”

The outcomes of interest in this analysis were pCR, EFS in patients with and without pCR, and adverse AEs.

Reference

Villacampa G, Navarro V, Matikas A, et al. Neoadjuvant Immune Checkpoint Inhibitors Plus Chemotherapy in Early Breast Cancer: A Systematic Review and Meta-Analysis. JAMA Oncol. Published online August 29, 2024. doi:10.1001/jamaoncol.2024.3456