Neoadjuvant immune checkpoint inhibitor therapy improves outcomes in early breast cancer
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Key takeaways:
- Adding immune checkpoint inhibitors to neoadjuvant chemotherapy benefited certain patients with early-stage breast cancer.
- Researchers observed no benefit with adjuvant immune checkpoint inhibitor therapy.
The addition of immune checkpoint inhibitor therapy to neoadjuvant chemotherapy improved pathologic complete response and EFS for certain patients with early-stage breast cancer, according to a systematic review and meta-analysis.
However, use of neoadjuvant immune checkpoint inhibitors resulted in a higher rate of grade 3 or worse adverse events.
“These emerging insights could help to better personalize treatment and improve patient selection in future trials,” Guillermo Villacampa, MSc, biostatistician at SOLTI Cancer Research Group and Vall d’Hebron Institute of Oncology in Spain, and colleagues wrote.
Background and methods
Multiple clinical trials have evaluated the benefits of adding immune checkpoint inhibitors to neoadjuvant chemotherapy for various breast cancer subtypes, and some studies have examined the impact of extending immunotherapy to the adjuvant setting.
However, the optimal approach for integrating immune checkpoint inhibitor therapy into treatment for early-stage breast cancer — taking cost and potential toxicity into account — has not been established, according to study background.
Villacampa and colleagues used the PubMed database to conduct a systematic review and meta-analysis of randomized clinical trials that evaluated PD-1 and PD-L1 immune checkpoint inhibitor therapy with chemotherapy vs. chemotherapy alone for patients with early-stage breast cancer.
The analysis included nine clinical trials with a combined 5,114 patients. More than half (54.8%) had received neoadjuvant immune checkpoint inhibitors.
Pathologic complete response (pCR) and EFS served as primary endpoints.
Safety and response based on PD-L1 status and cancer phenotype served as secondary endpoints.
Results and next steps
Use of immune checkpoint inhibitors improved the pCR rate among patients with triple-negative breast cancer (59.9% vs. 46.6%; OR = 1.64; 95% CI, 1.19-2.25). The benefit persisted regardless of PD-L1 status.
Immune checkpoint inhibitor therapy also improved EFS among patients with triple-negative breast cancer (HR = 0.69; 95% CI, 0.57-0.84), with a higher percentage of patients who received immunotherapy remaining event free at 5 years (80% vs. 71.8%).
Individuals with triple-negative breast cancer who achieved pCR had better EFS with immune checkpoint inhibitors than without (HR = 0.65; 95% CI, 0.42-1). They also had a higher 5-year EFS rate (92% vs. 88%).
Use of immune checkpoint inhibitors also improved EFS (HR = 0.77; 95% CI, 0.61-0.98) and 5-year EFS (63.% vs. 56.1%) among patients who had residual disease.
Adjuvant immune checkpoint inhibitors did not 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,” researchers wrote.
Patients with hormone receptor-positive/ERBB2-negative tumors who received neoadjuvant immune checkpoint inhibitors achieved a higher pCR rate (24.6% vs. 14.8%; OR = 1.87; 95% CI, 1.49-2.36). However, much of the benefit came from the subgroup of patients with PD-L1-positive tumors.
Subgroup analysis based on ER expression revealed use of immune checkpoint inhibitors did not affect pCR for patients with ERBB2-positive tumors.
Overall, patients who received neoadjuvant immune checkpoint inhibitors more often developed grade 3 or worse adverse events (63.6% vs. 54.1%) and discontinued any drug due to adverse events (20.4% vs. 12.2%).
Researchers acknowledged study limitations, including lack of individual patient data, and differences in survival definitions and drug combinations used in the analyzed 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 wrote.
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