In metastatic TNBC with germline or somatic BRCA mutation, when is the preferred time to introduce a PARP inhibitor?

First line PARPi for a gBRCA mutated metastatic TNBC should be considered if the PDL1 expression is too low or clinical considerations preclude 1st line checkpoint therapy. After the PARPi in this situation, I would consider sacituzumab or a clinical trial with other DNA damage response targeting ag...

This depends on which therapies the patient has already received, which could have included adjuvant olaparib for failure to achieve a complete pathologic response. If the cancer is PDL1 positive (CPS greater than or equal to 10%), I would first use a cytotoxic chemotherapy in combination with pembr...

When performance status or specific toxicities of immunotherapy are an issue, a PARP inhibitor may be a better option, as well as in cases where PD-L1 CPS<10.

For me, first line if CPS <10, and second line if CPS =/>10, assuming no contraindication to IO. I would also try to avoid allowing the tumor to develop resistance to a platinum prior to exposure to PARPi.

Regardless of germline BRCA status, first line recommended systemic therapy for metastatic TNBC patients with a PD-L1 CPS equal to or >10, is pembrolizumab plus chemotherapy (albumin-bound paclitaxel, paclitaxel, or gemcitabine and carboplatin. (NCCN 2023)

If PD-L1 CPS <10 and positive for germline ...

First line if CPS is less than 10, otherwise second line.