A systematic review and meta-analysis published in JAMA Oncology indicates that the addition of immune checkpoint inhibitors to neoadjuvant chemotherapy improves outcomes for patients with early-stage breast cancer, particularly those with triple-negative disease. The research, led by Guillermo Villacampa from the SOLTI Cancer Research Group, suggests that preoperative immunotherapy may offer significant benefits by priming the immune response and eradicating micrometastatic disease.
The meta-analysis included nine clinical trials encompassing 5,114 patients, with over half receiving neoadjuvant immune checkpoint inhibitors. The primary endpoints were pathologic complete response (pCR) and event-free survival (EFS).
Improved pCR and EFS in Triple-Negative Breast Cancer
The study found that immune checkpoint inhibitors significantly improved the pCR rate in patients with triple-negative breast cancer (59.9% vs. 46.6%; OR = 1.64; 95% CI, 1.19-2.25). This benefit was observed irrespective of PD-L1 status. Furthermore, EFS was also improved in this subgroup (HR = 0.69; 95% CI, 0.57-0.84), with a higher percentage of patients remaining event-free at 5 years (80% vs. 71.8%).
"These emerging insights could help to better personalize treatment and improve patient selection in future trials," Villacampa and colleagues wrote.
Impact of pCR and Residual Disease
Among patients with triple-negative breast cancer who achieved pCR, those treated with immune checkpoint inhibitors had better EFS compared to those who did not receive immunotherapy (HR = 0.65; 95% CI, 0.42-1), with 5-year EFS rates of 92% and 88%, respectively. Immune checkpoint inhibitors also improved EFS (HR = 0.77; 95% CI, 0.61-0.98) and 5-year EFS (63.6% vs. 56.1%) in patients with residual disease.
Limited Benefit in Adjuvant Setting
The analysis revealed that adjuvant immune checkpoint inhibitors did not significantly affect survival for patients with triple-negative breast cancer. "These results support the preference for preoperative immunotherapy, which — owing to the release of neoantigens from the tumor tissue — leads to priming of the immune response and eradication of micrometastatic disease," the researchers noted.
Outcomes in Hormone Receptor-Positive/ERBB2-Negative Tumors
Patients with hormone receptor-positive/ ERBB2-negative tumors who received neoadjuvant immune checkpoint inhibitors showed a higher pCR rate (24.6% vs. 14.8%; OR = 1.87; 95% CI, 1.49-2.36), particularly in the PD-L1-positive subgroup. However, immune checkpoint inhibitors did not affect pCR in patients with ERBB2-positive tumors.
Adverse Events and Future Directions
Neoadjuvant immune checkpoint inhibitors were associated with a higher incidence of grade 3 or worse adverse events (63.6% vs. 54.1%) and drug discontinuation due to adverse events (20.4% vs. 12.2%). The researchers acknowledged limitations such as the lack of individual patient data and variations in survival definitions and drug combinations across trials.
"Given the financial and toxicity costs associated with immune checkpoint inhibitors, future research should prioritize identifying patients most likely to benefit from the addition of [these agents] to neoadjuvant chemotherapy," Villacampa and colleagues concluded.
