Editors' ChoiceCancer

Boosting immune responses against early breast cancer

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Science Translational Medicine  18 Mar 2020:
Vol. 12, Issue 535, eabb2773
DOI: 10.1126/scitranslmed.abb2773


Pembrolizumab combined with neoadjuvant chemotherapy improves therapeutic responses in patients with early triple-negative breast cancer.

Immune checkpoint inhibitors such as antibodies against programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), which enhance anticancer immune responses, have become a pivotal approach to cancer therapy. One of these inhibitors, pembrolizumab, is an anti–PD-1 antibody approved for an increasing number of malignancies. Triple-negative breast cancer is generally an aggressive tumor type with a high risk of recurrence. Immune checkpoint inhibitors in combination with chemotherapy are currently approved only for patients with advanced or metastatic triple-negative breast cancer expressing PD-L1 on immune cells. In contrast, the role of anti–PD-1 and anti–PD-L1 antibodies in the treatment of early breast cancer has not yet been established.

Schmid et al. conducted a phase III clinical trial (KEYNOTE-522) in 1174 patients with newly diagnosed, previously untreated, nonmetastatic (early) triple-negative breast cancer, who were randomized in a 2:1 ratio to receive either pembrolizumab or placebo in addition to neoadjuvant (preoperative) chemotherapy. After surgery, in the adjuvant phase, patients received radiation therapy and pembrolizumab or placebo for up to nine cycles. The KEYNOTE-522 study showed that the pembrolizumab combination regimen improved the pathological complete response (pCR) at the time of surgery in all patients regardless of PD-L1 expression in their tumors. This treatment was generally well tolerated, although severe rashes, infusion reactions, and immune-related adrenal insufficiency were more frequently observed in the pembrolizumab-combination arm.

The increased rate of pCR with the addition of pembrolizumab was observed in all planned subgroups, including in patients with low PD-L1 expression, indicating that PD-L1 expression on tumor or immune cells is not a good predictive biomarker in itself and that clinical trials assessing immune checkpoint inhibitors should not exclude patients based only on this characteristic. Although much remains to be done to optimize the immune checkpoint therapeutic strategies in the treatment of breast cancer, the KEYNOTE-522 trial findings provide an important step forward for patients with early triple-negative breast cancer, and these results are likely to change the current treatment guidelines.

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