Congress highlights

SABCS 2022: focus on CDK4/6 inhibitors

By Heather L. Mason

Main takeaways:

• Despite similar mechanisms of action, not all CDK4/6 inhibitors are the same
• Initiation of chemotherapy might be delayed in certain patients
• There are multiple resistance mechanisms to CDK4/6 inhibitors, which may coexist in single patients

• Results of the DESTINY Breast04 clinical trial for trastuzumab deruxtecan (T-DXd) for HER2-low breast cancer
• Updates on clinical trials for CDK4/6 inhibitors
• Personalising treatment for HR+/HER2− breast cancer

CDK4/6 inhibitor new data and clinical implications

CDK4/6 inhibitor approvals in Europe and the US

Hot topics from ASCO 2021

Following ASCO 2021, Professor Nadia Harbeck, the Head of the Breast Cancer Centre at LMU University in Munich, Germany, shared her views on the thought-provoking discussions and exciting updates presented at the congress.

Exciting updates included results from ADAPTlate, a phase III trial that aimed to evaluate whether abemaciclib + endocrine therapy (ET) is superior to ET alone for patients at high risk for late disease recurrence, who have previously received locoregional therapy and are under adjuvant ET¹.

Translational research carried out in this study also aimed to assess the potential mechanisms of resistance to ET as well as CDK4/6 targeted therapy¹.

Professor Harbeck also discusses the phase III OlympiA trial. This trial investigated olaparib, a PARP inhibitor, as an adjuvant treatment in patients with germline BRCA mutant (gBRCAm) high-risk HER2-negative early breast cancer (EBC), who have previously completed primary local treatment and (neo)adjuvant chemotherapy¹.

Early breast cancer

One of the important topics discussed at ASCO 2021 was the use of CDK4/6 inhibitors in EBC. Watch below to see a summary of the exciting new developments from subgroup analyses of the Penelope-B and Monarch-E trials with Professor Harbeck.

Introduction

The annual San Antonio Breast Cancer Symposium (SABCS) was held virtually for the very first time in December 2020 and presented the latest state-of-the-art information on breast cancer. This year, SABCS 2020 comprised of a five–day program attended by a broad international audience and included the first results from the PENELOPE-B trial and the final invasive disease-free survival (IDFS) analysis of monarchE. Results from the prospective multicenter RISAS trial and correlative biomarker analysis of intrinsic subtypes and efficacy across the MONALEESA Phase III studies were also presented amongst other topics.

Professor Harbeck from the Breast Centre at LMU in Munich, Germany shares her thoughts on the most important data and discussions to emerge from SABCS 2020.

Key trial updates and new data from the ADAPT and ASCENT trials presented at SABCS 2020

Amongst the most important data that emerged from SABCS 2020 were from Dr Nadia Harbeck who presented data from the ADAPT trial (NCT01779206)¹ and showed that certain patients with luminal EBC and up to 3 involved lymph nodes can be treated with adjuvant endocrine therapy (ET) according to the primary outcome analysis. The patients in the analysis had luminal EBC and were candidates for adjuvant chemotherapy. All patients received preoperative standard ET followed by adjuvant therapy alone. The patients were split into groups by recurrence score (0 to 11 and 12 to 25) and ki67 expression level, and both showed a response to preoperative ET, determined by a 10% or lower ki67 expression level.

The 5–year IDFS rate for patients with recurrence scores of 0 to 11 was also non-inferior to patients with recurrence scores of 12 to 25 (93.9% vs 92.6%, respectively), as was the 5–year distant disease-free survival (dDFS) rate (96.3% vs 95.6%, respectively) and 5–year overall survival (OS) rate (98/8% vs 97.3%, respectively). The 5–year dDFS did not differ by age or nodal subgroups either and a conclusion was reached that, irrespective of age, patients with 0 to 3 involved lymph nodes and a recurrence score of 0 to 11 as well as patients with a limited nodal burden and a recurrence score of 12 to 25 (and endocrine response after short perioperative ET) can be treated by ET alone.

In the metastatic breast cancer setting, Dr Sara Hurvitz discussed additional results from the phase III ASCENT trial (NCT02574455)² which showed favourable outcomes with sacituzumab govitecan in patients with triple-negative breast cancer regardless of their biomarker status. Sacituzumab govitecan extended the OS and improved the overall response and clinical benefit rates compared to the treatment of choice. Sacituzumab govitecan showed an OS with a median of 12.1 months (95% CI, 10.7–14.0) versus 6.7 months (95% CI, 5.8–7.7) for chemotherapy, with a hazard ratio (HR) of 0.48 (95% CI 0.38-0.59; p<0.0001). Moreover, the KEYNOTE355 trial updates highlighted a benefit in previously untreated patients with inoperable or metastatic triple-negative breast cancer after adding pembrolizumab to chemotherapy. For the overall study population, the addition of pembrolizumab to chemotherapy reduced the risk of disease progression by 18% (HR, 0.82; 95% CI, 0.69–0.97), and a reduced risk of disease progression in patients who received pembrolizumab was also observed.