Early local therapy fails to extend survival in metastatic breast cancer subset
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Early local therapy did not prolong survival among women with de novo metastatic breast cancer and intact primary tumors, according to randomized phase 3 study results presented during the ASCO20 Virtual Scientific Program.
Results revealed a 2.5-fold greater risk for local disease progression without locoregional treatment; however, locoregional treatment of the intact primary tumor did not appear associated with improved health-related quality of life.
“Based on available data, locoregional treatment for the primary tumor should not be offered to women with stage IV breast cancer with the expectation of a survival benefit,” Seema Ahsan Khan, MD, professor of surgery at Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center at Northwestern University, said during a presentation. “When systemic disease is well-controlled with systemic therapy but the primary site is progressing, locoregional therapy may be considered.”
Approximately 6% of patients with newly diagnosed breast cancer present with stage IV disease and intact primary tumors.
Retrospective analyses suggested locoregional treatment may extend survival.
A meta-analysis of 19 retrospective studies showed a pooled HR of 0.69 favoring surgical resection of the primary tumor in stage IV disease; Khan said. However, these studies were biased, as women who underwent surgery were younger, had smaller tumors, and were more likely to have hormone receptor-positive disease and lower metastatic burden.
Data from prior randomized trials that tested the value of locoregional treatment in this setting are inconsistent.
Khan and colleagues with the ECOG-ACRIN Cancer Research Group conducted the E2108 trial to assess the value of locoregional therapy for intact primary tumors after initial systemic therapy.
Researchers enrolled 390 women with de novo stage IV disease between February 2011 and July 2015.
Per protocol, women received optimal systemic therapy based on individual and tumor characteristics, and 256 women (median age, 56 years; range, 25-86) who did not progress in the 4 to 8 months after optimal systemic therapy proceeded to randomization.
Initial systemic therapies included endocrine therapy only (31.2%), chemotherapy and HER2-directed therapy (53.8%), and both endocrine therapy and chemotherapy (15%). A comparable percentage of women had primary tumors that were T1-3/N0-1 (52%) or T4 and/or N2-3 (48%).
About one-third (37.9%) had bone metastases only, 24.2% had visceral metastases only and the remainder had both.
Researchers assigned 125 women to early local therapy; of these, 109 underwent surgery, 87 achieved free surgical margins and 74 received locoregional radiotherapy.
The other 131 women continued with systemic therapy alone. Twenty-five women in this group underwent surgery — 13 in the year after randomization and 12 at a later time.
The local therapy and continued systemic therapy groups were balanced with regard to median age (55 years vs. 56 years) and race/ethnicity (European ancestry, 82% each), as well as percentage of women with hormone receptor-positive/HER2-negative disease (59% vs. 57%), triple-negative disease (7.8% vs. 9.1%) and HER2-positive disease (33% vs. 33.9%).
OS served as the primary endpoint. Secondary endpoints included time to locoregional disease progression, health-related quality of life and burden of circulating tumor cells.
Investigators designed the trial to detect an improvement in 3-year OS rate from 30% with optimal systemic therapy alone to 49.3% with the addition of locoregional therapy. They expected to have complete information after 152 deaths.
Overall crossover between treatment groups was 14%, which was comparable with the planned rate of 15%, Khan said.
After median follow-up of 59 months (range, 0-91), 121 women died and 43 experienced locoregional progression events.
Researchers reported no significant difference in 3-year OS between women who received or did not receive locoregional therapy (68.4% vs. 67.9%; HR = 1.09; 90% CI, 0.8-1.49).
OS analyses by tumor subtype in the early local therapy group revealed HRs of 3.5 (95% CI, 1.16-10.57) for women with triple-negative disease (n = 20), 1.05 (95% CI, 0.49-2.24) for those with HER2-positive disease (n = 79) and 0.94 (95% CI, 0.59-1.51) among those with hormone receptor-positive, HER2-negative disease (n = 137).
Results also showed no statistically significant difference in PFS.
Researchers also assessed locoregional progression, defined in the continued systemic therapy group as development of symptoms that led to a decision for local therapy, and defined in the early local therapy group as regional nodal progression, chest wall disease or invasive in-breast recurrence.
Women who received optimal systemic therapy alone appeared more than twice as likely to develop locoregional recurrence or progression within 3 years (25.6% vs. 10.2%; HR = 0.37; 95% CI, 0.19-0.73).
Health-related quality of life as assessed by the FACT-B Trial Outcome Index was significantly worse among women who received locoregional therapy at 18 months after randomization (Wilcoxon rank sum test P = .01); however, no significant differences were observed at 6 months or 30 months.
“However, it should be noted that there was a diminution in the amount of data as the trial progressed, as 206 women reported quality-of-life surveys at baseline and, by 30 months, this had declined to 111 women,” Khan said. “These quality-of-life data are not quite as robust as we would have liked.” – by Mark Leiser
Reference:Khan SA, et al. Abstract LBA2. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
Disclosures: ECOG funded this study. Khan reports no relevant financial disclosures. Please see the abstract for all other researchers’ relevant financial disclosures.
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Khan SA, et al. Abstract LBA2. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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