Abstract OT2-15-01: COntinue the SaMe systemic therapy after local ablative therapy for Oligoprogression in metastatic breast cancer - the COSMO study
Authors: Almekinders Cornelia AM , Steenbruggen Tessa G , Mandjes Ingrid A. , Lopez-Yurda Marta , Bos Monique EMM , Wiersma Terry G , Sonke Gabe S. 
Published: March 2023

Background

Patients with metastatic breast cancer (MBC) are usually treated with palliative systemic therapy until progression or unacceptable toxicity. When progression occurs, clinicians typically switch to the next line of systemic therapy. However, this strategy might be suboptimal in case of mixed response or oligoprogression. Oligoprogression refers to a situation in which inter-lesion heterogeneity causes one or few metastatic lesions to progress while the vast majority of the metastatic burden responds to the treatment. Locally ablative treatment of the progressive lesion(s) with radiotherapy, resection or radiofrequency ablation may enable continuation of otherwise effective systemic treatment. Solid data to support this approach, however, is lacking at this moment.

Study design

The COSMO study is an investigator-initiated single-arm phase 2 study. It is intended to be a multicenter study.

Eligibility criteria

Patients with MBC and oligoprogression, defined as 1-2 progressive lesions while the majority of the metastatic burden remains stable or in remission, are eligible. Current systemic therapy must be 1st or 2nd line and patients must have responded to this systemic therapy for at least six months prior to the occurence of oligoprogression. The aberrant lesion must be amenable to locally ablative therapy. All eligibility criteria may be found in table 1: eligibility criteria. Aim To investigate efficacy of local ablation of aberrant lesions combined with continuation of the same systemic therapy in patients with oligoprogression of MBC.

Primary endpoint:

Progression-free survival rate at six months (PFS-6).

Secondary endpoints:

- PFS

- Overall survival

- Time to next line of systemic therapy

Primary and secondary endpoints will also be stratified by localization of progressive lesion and BC subtype (ER+/HER2- vs. HER2+ vs. TN).

- Local control rate of lesion treated with LAT at 12 months

- Complications due to LAT

- Quality of life

- Incidence of visceral crisis

Exploratory endpoints:

- Biomarkers, including receptor (ER/PR/HER2), PD-L1 and gene expression patterns in biopsies from progressive and responding lesions

- Prognostic value of ctDNA at oligoprogression and during the course of treatment

Statistical methods

An A’hern design was chosen to conduct this study. As null-hypothesis (H0), PFS-6 rate ≤ 25% is set. The alternative hypothesis (H1) is PFS-6-rate ≥ 40%. Hypotheses were set to meet criteria for clinical significance, as stated by experts in the field. Setting one-sided α = 0.05 and a desirable power=95%, 107 evaluable patients are needed. To account for 10% of the patients to be unevaluable, 118 included patients are needed. An early stopping rule for safety is applicable: if out of the first 45 patients ≥4 of these patients have developed visceral crisis, the study will be closed early.

Accrual

Start: July 2022

Target: 118 patients

Estimated accrual time: 2-3 years

Further information

Corresponding author: c.almekinders@nki.nl

Clinicaltrials.gov identifier: NCT05301881

This study is funded by the Maarten van der Weijden foundation.

This study was developed during the 21st EORTC/ESMO/AACR workshop on methods in clinical cancer research (MCCR).

Table 1. Eligibility criteria.

Citation Format: Cornelia AM Almekinders, Tessa G Steenbruggen, Ingrid A. Mandjes, Marta Lopez-Yurda, Monique EMM Bos, Terry G Wiersma, Gabe S. Sonke. COntinue the SaMe systemic therapy after local ablative therapy for Oligoprogression in metastatic breast cancer - the COSMO study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-15-01.