Early Local Therapy Survival Benefit Refuted For De Novo Metastatic Breast Cancer

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Early locoregional therapy (LRT) does not significantly improve overall survival (OS), progression-free survival (PFS) or health-related quality of life (HRQoL) in women with de novo metastatic breast cancer, the ECOG-ACRIN 2108 investigators have found. 

The results were reported by Seema Khan, from Northwestern University in Chicago, Illinois, USA, at the virtual 2020 ASCO Annual Meeting. She explained that the ECOG-ACRIN 2108 trial was launched following conflicting results on the benefit of LRT for the intact primary tumour in this patient population.  

A total of 390 patients were recruited and began 4–8 months of optimal systemic therapy; patients who did not experience distant disease progression were then randomly assigned to receive early LRT (n=125) – consisting of complete tumour resection and postoperative radiation, as per guidelines for women with nonmetastatic breast cancer – followed by systemic therapy, or systemic therapy alone (n=131). 

Patients who did and did not undergo randomisation were comparable in terms of age, ethnicity/race, menopausal status, site of metastatic disease, initial systemic therapy received and most primary tumour characteristics. But randomised patients were more likely to have HER2-positive disease and less likely to have triple-negative disease than those who did not continue in the trial, and were also significantly less likely to have direct invasion into skin or skin nodules. 

Moreover, patients in the two randomised arms were comparable in terms of age, ethnicity/race and breast cancer subtype, Seema Khan explained. Of the patients given early LRT, 109 underwent surgery, 87 achieved negative surgical margins and 74 received locoregional radiation, while 25 of the systemic therapy only arm underwent surgery. 

After a median 53 months of follow-up, OS was a median 54 months for both treatment arms with superimposable survival curves, “with no hint here of an advantage in terms of survival with the use of early locoregional therapy for the primary site”, the presenter said. 

When assessed by tumour subtype, the 20 patients with triple-negative breast cancer had significantly poorer OS with early LRT than without (hazard ratio [HR]=3.50), and there was no significant difference between the arms for the 79 HER2-positive patients and the 137 patients with hormone receptor-positive, HER2-negative disease. 

And PFS curves also overlapped for the two treatment arms.  

However, 10.2% of the patients who received early local therapy experienced locoregional progression, defined as regional nodal progression, or chest wall disease or invasive in-breast recurrence, compared with 25.6% of the systemic therapy only group, for whom locoregional progression was defined as symptoms leading to local therapy. This gave a significant HR for locoregional progression of 0.37 in favour of early LRT. 

“Although we saw a 2.5-fold higher risk of local disease progression without locoregional therapy, the use of LRT for the primary site did not lead to improved quality of life”, Seema Khan commented.  

Indeed, patients given early LRT had significantly poorer HRQoL at 18 months of follow-up, as measured by the FACT-B Trial Outcome Index, albeit there was no difference at any other timepoint. 

“Based on available data, LRT for the primary tumour should not be offered to women with stage IV breast cancer with the expectation of a survival benefit”, the presenter concluded.  

“When systemic disease is well controlled with systemic therapy but the primary site is progressing, as does happen occasionally, locoregional treatment may be considered”, she added. 

Seema Khan concluded by reminding delegates that results from the JCOG-1017 trial of early LRT in a similar group of 507 patients are expected in May 2022. “We look forward with great interest to those results”, she said. 

Reference  

Khan SA, Zhao F, Solin LJ, et al. A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108). J Clin Oncol; 38: (suppl; abstr LBA2). DOI: 10.1200/JCO.2020.38.18_suppl.LBA2