KEYLYNK-009: Is Olaparib Plus Pembrolizumab a Viable Maintenance Strategy in Metastatic Triple-Negative Breast Cancer?

Introduction: The Challenge of Metastatic Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer, characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression. Historically, the management of metastatic TNBC (mTNBC) relied heavily on cytotoxic chemotherapy. However, the landscape has shifted with the introduction of immune checkpoint inhibitors (ICIs) and poly(ADP-ribose) polymerase (PARP) inhibitors.

The KEYNOTE-355 trial established the combination of pembrolizumab, an anti-PD-1 therapy, plus chemotherapy as a standard of first-line treatment for patients with PD-L1-positive mTNBC. Despite this progress, the duration of response is often limited, and the cumulative toxicity of continuous chemotherapy poses a significant challenge to patient quality of life. The KEYLYNK-009 study was designed to address this by exploring a switch-maintenance strategy, substituting chemotherapy with the PARP inhibitor olaparib in patients who achieved clinical benefit from initial chemo-immunotherapy.