ESTRO 2025 - Abstract Book

S42

Invited Speaker

ESTRO 2025

Abstract: New systemic therapies are coming at hand for treating breast cancer (BC) patients both in the adjuvant and metastatic settings. In this presentation, focus is on combining radiation therapy (RT) with antibody drug conjugates (ADC) and CDK4/6 inhibitors (CDK4/6i). Using systemic therapy concomitant with RT means that RT is provided within 5 half-lives of the drug, thus sequential RT is when the drug is separated by >5 times T 1/2 . Despite the frequent use of these drugs in BC patients also treated with RT, there is surprisingly limited data on the concomitant use of the drugs with RT. Currently, ADC include trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan. Data from the Katherine and ATEMPT trials testing T-DM1 in the adjuvant setting documented a slightly higher risk of radiation pneumonitis with T-DM1 compared to trastuzumab (1.5% vs 0.7%). No cardiac safety issues have been reported with T-DM1 used concomitantly with RT. The ESTRO consensus supports the concomitant use of T-DM1 with adjuvant RT, and it may also be used in the palliative situation for selected patients. T-DXd has become standard palliative therapy in both HER2+ and HER2 low BC patients, since it prolongs progression free survival. In the first randomized phase III trial using T-DXd (the Destiny-Breast03 trial) palliative RT (excluding the lung area) was permitted concomitantly with T-DXd, but adverse effects were unfortunately not reported. There is no prospectively collected safety data available on T-DXd concomitant with RT. Sacituzumab govitecan (trodelvy) has in several trials proven potential to significantly prolong progression free survival and overall survival, however, in these trials RT was prohibited within 2-4 weeks prior to randomization and not allowed concomitantly with the drug. Only very little data is available on the concomitant use of Sacituzumab govitecan with RT, thus there is no support for the concomitant use of Sacituzumab govitecan with RT outside clinical trials. CDK4/6i include abemaciclib, ribociclib and palbociclib, where the evidence is in favor of using these drugs for first line metastatic therapy of selected patients with hormone positive BC. Recently, longer follow up data on using abemaciclib for selected high-risk BC patients have paved the way for using abemaciclib as standard for adjuvant therapy of BC patients diagnosed with pN2-3 or pN1 combined with ether grade III or T3 tumour. In the pivotal trials paving the way for standard use of CDK4/6i in the metastatic setting, the recommendation was to not use CDK4/6i concomitantly with RT. Only the MONELEESA trials accepted palliative RT but only for bone pain relief, thus mostly single fraction with relatively low dose. In the MonarchE trial demonstrating improved invasive disease-free survival and distant relapse-free survival, concomitant adjuvant RT was not allowed with abemaciclib. Several single institution retrospective studies have reported outcome in favor of using CDK4/6i concomitantly with RT for palliative purpose in selected BC patients. Overall, there is unfortunately limited data supporting concomitant use of the newer anti-cancer drugs for BC patients also treated with RT. Few trials have investigated the adverse effects from this combination, whilst most trials have had the combined treatment as an exclusion criterium. When combining drugs with concomitant RT the recommendation is always to be cautious, even in patients where the combination is considered feasible, thus the patient and staff should be aware of the risk of serious adverse effects, e.g. pneumonitis.

4717

Speaker Abstracts Novel systemic therapies effective on brain metastases: New paradigms and their potential influence on local therapies Giuseppe Curigliano Oncology and Hemato-Oncology, University of Milano, European Institute of Oncology, IRCCS, Milano, Italy

Abstract:

Patients with HER2-positive breast cancer have a significant risk of developing brain metastases (BrM), which have detrimental effects on survival outcomes and quality of life. Although there are several systemic treatment options