|The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
According to results of a randomized, multicenter, phase 3 trial, the overall survival (OS) and long-term health-related quality of life (HRQoL) of patients diagnosed with de novo metastatic breast cancer (MBC) characterized by an intact primary tumor were not improved by early locoregional treatment with therapeutic intent compared with standard palliative treatment. These findings were presented during the plenary session of the ASCO20 Virtual Scientific Program.
In the United States, only about 6% of patients with breast cancer have stage IV disease with an intact primary tumor at the time of diagnosis. However, evidence is conflicting regarding whether or not early locoregional treatment, including therapeutic, conventional surgery with or without radiation therapy, of an intact primary tumor has a positive effect on survival compared with standard palliative therapy in the setting of de novo metastatic breast cancer.
In this study (Eastern Cooperative Oncology Group-American College of Radiology Imaging Network [ECOG-ACRIN] 2108; ClinicalTrials.gov Identifier: NCT0124280), patients with de novo MBC and an intact primary tumor who did not experience disease progression at distant sites over the 4 to 8 month period during which they received treatment with an optimal systemic therapy regimen were randomly assigned in a 1:1 ratio to undergo locoregional treatment of the intact primary tumor versus not. The primary study endpoint was overall survival (OS), with secondary study endpoints including locoregional disease control, time to locoregional progression, and HRQoL as measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) Trial Outcome Index.
Of the 256 patients eligible for study randomization, 125 patients received early locoregional treatment plus optimal systemic therapy while 131 patients received optimal systemic therapy alone. Treatment arms were well balanced with respect to patient age, race, menopausal status, disease burden, and hormone receptor and HER2 tumor status.
Median patient age was approximately 56 years and about two-thirds of patients were classified as postmenopausal.
Of the 125 patients randomly assigned to the early locoregional treatment arm, 107 (86%) underwent early surgery with 87 (70%) achieving free surgical margins and 74 (59%) receiving locoregional radiation therapy. Of note, 25 (19%) of the 131 patients randomly assigned to the control arm underwent palliative surgery at some point during the study.
A key finding of this study was the absence of a significant difference in the rates of 3-year OS for patients assigned to the intervention (68.4%) and comparator study arms (67.9%; hazard ratio [HR], 1.09; 90% CI, 0.80-1.49; log rank P =.63). At a median follow-up of 53 months, median OS for the overall study population was 54 months.
“There is no hint here in terms of a survival advantage with the use of early locoregional therapy for the primary site,” stated Seema A. Khan, MD, Professor of Surgery at the Robert H. Lurie Cancer Center of Northwestern University in Chicago, Illinois, and the presenting study author.
Similarly, no differences in OS were observed for subgroups of patients defined according to HER2-positive tumor status or hormone receptor-positive and HER2-negative tumor status when the study arms were compared.
Furthermore, no progression-free survival benefit (PFS) was observed for early locoregional treatment with optimal systemic therapy compared with optimal systemic therapy alone (P =.40).
Perhaps not surprisingly, the 3-year rate of recurrence/progression of locoregional disease was significantly lower in those who underwent early locoregional treatment (10.2%) compared with patients who did not (25.6%; HR, 0.37; 95% CI, 0.19-0.73).
Regarding measures of HRQoL, the percentages of patients completing the FACT-B questionnaire were 81%, 60%, and 51% at 6-, 18-, and 30-months following study randomization, respectively. Significantly worse HRQoL was observed at 18 months following study randomization in those undergoing early locoregional treatment plus optimal systemic therapy versus optimal systemic therapy alone (P =.001), however no significant differences in HRQoL between study arms were observed at 6 months and 30 months post-randomization.
In her concluding comments, Dr Khan noted that “based on available data, locoregional therapy to the primary tumor should not be offered to women with stage IV breast cancer with the expectation of a survival benefit.”
Disclosures: Research funding for this study was provided by the Eastern Cooperative Oncology Group. For a full list of disclosures please refer to the original study.
Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.
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). Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr LBA2.