LBA8: KEYNOTE-522: Phase 3 Study of Pembrolizumab + Chemotherapy versus Placebo + Chemotherapy as Neoadjuvant Treatment, Followed by Pembrolizumab versus Placebo as Adjuvant Treatment for Early Triple-Negative Breast Cancer (TNBC) Schmid et al.
LBA9: Phase 3 study of veliparib with carboplatin and paclitaxel in HER2-negative advanced/metastatic gBRCA-associated breast cancer: BROCADE3 Dieras et al.
Discussion of KEYNOTE-522 and BROCADE3
Phase 3 Studies and take home messages
Summary of BROCADE3
- Veliparib+Carbo+Paclitaxel followed by veliparib continuation monotherapy significantly improved PFS in germline BRCA associated BCs.
- Main AE was ≥3 Thrombocytopenia (40% vs 28%)
- Veliparib monotherapy was well tolerated
- No significant OS benefit (analysis immature)
- Hard to know if the effect observed is due to upfront V-chemo combination and/or continuation phase of monotherapy
Summary of KEYNOTE-522
- KN522 shows statistically significant improvement when pembrolizumab is added to a solid neoadjuvant control arm
- Carbo control arm pCR is about right
- Promising but very early EFS: unclear what a pCR increase with IO will translate to EFS improvement.
- High rates of PD-L1 positivity in early stage >80% (unlike late stage >40% SP142)
- PD-L1 pos vs neg effects
- ? Role of assay, role of chemotherapy, pCR rates in higher CPS scores?
Many other questions are raised such as:
- Do all early stage TNBC need AC-TC-pembro?
- Working out Dose and scheduling
- Chemo: what is additive or synergistic or even detrimental?
- IO agents: what is the best scheduling and duration of PD-(L)1 agents ?
- Further biomarker analysis – TIL composition, WES, germline BRCA status, TNBC subtypes