basket study for oligo-metastatic breast cancer

Conditions: HER2-positive Breast Cancer

Summary: the study will include patients with her2-positive breast cancer and 1- 3 distant metastatic lesions, all amenable for curative intervention. patients will be stratified by prior therapy and er expression. in the initial baskets patients with be treated with trastuzumab-deruxtecan. patients are treated with t-dxd 5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. the first 8 cycles of t-dxd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment. the proposed m22bol trial is based on an important knowledge gap for regarding breast cancer patients with 'oligo-metastatic' disease who are usually not included in clinical trials for patients with metastatic disease since loco-regional treatments (radiation, surgery) with curative intent is not allowed in clinical trials for metastatic breast cancer. moreover, neo-adjuvant trial protocols for early breast cancer exclude patients with distant metastases that can be treated with curative intent. this basket trial evaluates t-dxd for oligo-metastatic breast cancer with the goal to induce deep responses and subsequently long-lasting disease remissions and potentially cure.

the study will include patients with her2-positive breast cancer and 1- 3 distant metastatic lesions, all amenable for curative intervention. patients will be stratified by prior therapy and er expression. given the basket-design of this trial other baskets for oligo-metastatic breast cancer can be added, such as but not limited to other breast cancer subtypes or with other promising drugs. baskets for de novo oligo-metastatic disease i. er+/her2+ ii. er-/her2+ baskets for oligo-metastatic disease after prior chemo/anti-her2 therapy for primary disease iii. er+/her2+ iv. er-/her2+

Eligibility criteria:
inclusion criteria: * histologic proof of infiltrating her2-positive breast cancer (as determined by ihc 3+ and/or amplification by ish)\[8\] * histologic or cytologic proof of breast cancer metastases (at least one lesion) * histologic determination of level of er-expression * oligo-metastatic disease as determined by standard of care diagnostics. the number of total individual distant metastases is limited to five, either in one organ or in 2-5 organ systems. clustered lymph nodes that can be irradiated with curative intent in a single field are defined as single lesion. pleuritis carcinomatosa, miliary spread of metastases (even within one organ), or peritoneal spread of metastases rules out oligo-metastatic disease and is not allowed. initial staging by pet-ct (whole body) and mri of breast and brain are mandatory, as is mri liver or spine and pelvis in case of liver or bone metastases respectively. * in case of recurrent disease, a disease-free interval of 24 months. * measurable disease according to recist1.1 * patients must be at least 18 years of age and be able to give written informed consent and comply with study procedures. * world health organization (who) performance status 0 or 1 exclusion criteria: * prior line of therapy for metastatic disease. exceptions are endocrine therapy or radiation considered to be part of the curative treatment, within 3 months before enrolment * leptomeningeal disease or central nervous metastases * clinically relevant obstruction or compression of spinal cord, central nervous, gastro-intestinal or cardiovascular system, that cannot be alleviated before start of treatment. * other malignancy, unless treated with curative intention and a long-term survival probability of \>95%, including in-situ or pre-malignant lesions.

Keywords: oligometastatic disease (max 3 lesions)