The first daily highlight on SABCS 2023 is done by Dr Kevin Punie, medical oncologist at the GZA Hospitals Sint-Augustinus, Antwerp. He selected four presentations from the general session 1 that took place on Wednesday, December 6th.
The first study presented by Shereen Loi focuses on a biomarker analysis of the phase 3 CheckMate 7FL trial, evaluating the addition of nivolumab to neoadjuvant chemotherapy and adjuvant endocrine therapy in HR+, HER2- breast cancer. The trial revealed a significant increase in pCR rates with the addition of nivolumab, particularly in patients with positive PD-L1 expression, higher stromal tumour-infiltrating lymphocytes (TILs), and lower estrogen receptor (ER) expression. The association between PD-L1 expression and PCR benefit was confirmed using different scoring systems. Moreover, stromal TILs were identified as a potential biomarker, indicating a threshold above 1% for significant benefit. The study also highlighted an inverse relationship between ER expression and nivolumab benefit, suggesting that patients with lower ER scores derived greater benefits.
The second presentation by Joyce O’Shaughnessy discusses a biomarker analysis from the Keynote 756 study, investigating pembrolizumab addition to neoadjuvant chemotherapy and adjuvant endocrine therapy in HR+, HER2- breast cancer. The study demonstrated an absolute increase in pCR rates, particularly in lymph node-positive patients. PD-L1 expression, assessed by combined positive score, correlated with increased PCR rates in both arms, indicating a benefit from chemotherapy and pembrolizumab combination. ER expression further influenced the benefit, with higher CPS scores showing increased benefits, contrary to triple-negative breast cancer findings. However, the need for long-term efficacy data before the standard implementation of immunotherapy in HR-positive, HER2-negative tumours is emphasized.
The third presentation by Hope Rugo discusses the KeyLynk-009 study, a Phase II trial evaluating pembrolizumab plus olaparib versus pembrolizumab plus chemotherapy as maintenance in first-line advanced triple-negative breast cancer (TNBC). The trial did not show significant improvements in PFS or OS in the overall population. However, a positive trend toward improved outcomes was observed in patients with tumour BRCA mutations, suggesting a potential benefit in this subgroup. The need for further confirmation and consideration of more selective PARP inhibitors is highlighted.
The fourth presentation covers the HER2CLIMB-02 study, a randomized trial investigating tucatinib plus TDM1 versus TDM1 alone in HER2-positive advanced breast cancer. The study demonstrated a statistically significant improvement in PFS with the tucatinib-TDM1 combination. However, overall survival data are immature, and concerns arise regarding hepatotoxicity, with a higher incidence in the combination arm. External validity is limited due to changes in standard of care, and the study suggests a potential benefit in patients with active brain metastases. The conclusion emphasizes the importance of considering the optimal tucatinib combination based on the HER2-CLIMB-01 trial results.
Loi S, SABCS 2023, #GS01-01
O’Shaughnessy J., SABCS 2023, #GS01-02
Rugo H., SABCS 2023, #GS01-05
Hurvitz S.., SABCS 2023, #GS01-10
With the educational support of: