Is immunotherapy used before a Poly (ADP-ribose) polymerase (PARP) inhibitor in Triple-Negative Breast Cancer (TNBC)?

From the Guidelines

Immunotherapy is used before a Poly (ADP-ribose) polymerase (PARP) inhibitor in Triple-Negative Breast Cancer (TNBC) for patients with PD-L1-positive tumors. The treatment sequence for TNBC depends on various factors, including PD-L1 expression, BRCA mutation status, disease stage, and prior treatments.

• For patients with PD-L1-positive tumors, immunotherapy with atezolizumab plus albumin-bound paclitaxel is a preferred option, as shown in the IMpassion 130 trial 1.
• This trial demonstrated a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) in patients with PD-L1-expressing tumors who received atezolizumab plus albumin-bound paclitaxel compared to those who received placebo plus albumin-bound paclitaxel.
• The use of PARP inhibitors, such as olaparib, is generally reserved for patients with germline BRCA mutations, regardless of prior immunotherapy use.
• The sequencing of these treatments is determined by the specific characteristics of the patient's cancer, rather than a fixed order of administration.
• It is essential to consider the individual patient factors, including BRCA mutation status, PD-L1 expression, and prior treatments, when deciding the treatment sequence for TNBC.
• The IMpassion 130 trial 1 provides evidence for the use of immunotherapy before PARP inhibitors in TNBC patients with PD-L1-positive tumors, highlighting the importance of PD-L1 expression in determining the treatment sequence.

From the Research

Immunotherapy and PARP Inhibitors in TNBC

• The use of immunotherapy before a Poly (ADP-ribose) polymerase (PARP) inhibitor in Triple-Negative Breast Cancer (TNBC) is explored in various studies 2, 3, 4, 5, 6.
• According to a case report, a patient with BRCA1 mutated TNBC was treated with pembrolizumab after olaparib, demonstrating successful treatment 2.
• The combination of chemotherapy and immunotherapy is a potential therapeutic option for PD-L1-positive metastatic TNBC, with the FDA approving atezolizumab and pembrolizumab in combination with chemotherapy 3.
• Immunotherapy has shown promise in TNBC, with phase III clinical trials demonstrating a progression-free survival benefit in metastatic PD-L1-positive TNBC patients treated with atezolizumab or pembrolizumab in combination with chemotherapy 4.
• The use of immunotherapy in combination with other treatments, such as traditional chemotherapy and new treatments like photodynamic therapy, may exert synergistic effects 5.
• PARP inhibitors, such as olaparib and talazoparib, have been approved for the treatment of germline BRCA mutation-associated breast cancer, and immunotherapy using checkpoint inhibitors has been approved for PD-L1-positive advanced TNBC 6.

Treatment Sequencing

• There is limited data to support the sequential use of immunotherapy following treatment with a PARP inhibitor 2.
• However, the case report presented in 2 demonstrates successful treatment of a patient with BRCA1 mutated TNBC treated with pembrolizumab after olaparib.
• The optimal sequencing of immunotherapy and PARP inhibitors in TNBC remains an area of ongoing research and investigation 3, 4, 5, 6.