Immunotherapy has improved outcomes for some people with triple-negative breast cancer ( TNBC) and is now a standard treatment in specific settings, while its role in hormone receptor–positive disease remains under study, according to a review published recently in Oncology.
The strongest evidence supports pembrolizumab combined with chemotherapy for patients with metastatic TNBC whose tumors have a PD-L1 combined positive score greater than 10, as well as for patients with newly diagnosed stage II or III TNBC treated before and after surgery.
Early studies tested pembrolizumab alone in heavily pretreated metastatic TNBC. In the phase 1 KEYNOTE-012 trial, the overall response rate was 18.5%, with several durable responses. However, the phase 3 KEYNOTE-119 trial did not show improved overall survival or progression-free survival compared with chemotherapy. Trials of atezolizumab, a PD-L1 inhibitor, produced mixed results.
Although IMpassion130 initially showed a 10.5-month overall survival improvement, later data led to withdrawal of its FDA approval. Subsequent studies, including IMpassion131 and IMpassion132, failed to confirm a survival benefit.
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The phase 3 KEYNOTE-355 trial established a new first-line standard for metastatic TNBC. Among patients with a PD-L1 combined positive score greater than 10, median progression-free survival was 9.7 months with pembrolizumab plus chemotherapy vs 5.6 months with chemotherapy alone. This benefit led to FDA approval of the regimen for this population.
Immunotherapy has also reshaped treatment for early-stage TNBC. In KEYNOTE-522, adding pembrolizumab to neoadjuvant chemotherapy increased pathologic complete response rates to 64.8% vs 51.2%. At 60 months, overall survival was 86.6% in the pembrolizumab group compared with 81.7% in the control group.
Benefits were seen even in patients with residual disease after surgery, although higher residual cancer burden was linked to greater recurrence risk. Other trials of atezolizumab in early-stage TNBC, including NeoTRIP and ALEXANDRA/IMpassion030, did not show the same benefit, raising questions about drug target, chemotherapy backbone and timing.
“Predictive biomarkers of immunotherapy benefit remain elusive,” the review authors wrote. “Immunotherapy does not come without risks; identifying patients who will benefit and those at risk for adverse effects is of paramount importance.”
For hormone receptor–positive, HER2-negative breast cancer, immunotherapy remains investigational. In KEYNOTE-756, pembrolizumab increased pathologic complete response rates to 24.3% vs 15.6%. In CheckMate-7FL, nivolumab improved rates to 24.5% vs 13.8%, with greater benefit in tumors expressing PD-L1 and in estrogen receptor–low disease. However, event-free survival data are not yet available, and combining immunotherapy with CDK4/6 inhibitors may increase risks such as pneumonitis and hepatitis.
For patients, these advances mean that immunotherapy can meaningfully improve the chance of tumor disappearance before surgery and may extend survival in certain high-risk groups. Testing tumors for PD-L1 and other biomarkers is increasingly important to determine who is most likely to benefit while avoiding unnecessary side effects.
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