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Treating primary tumor doesn’t improve OS in stage IV breast cancer



In patients with newly diagnosed stage IV breast cancer and an intact primary tumor, locoregional therapy after optimal systemic therapy does not improve survival or quality of life, results of the phase 3 E2108 trial suggest.

Among 256 patients with stage IV breast cancer with intact primary tumors who had no disease progression for 4-8 months after the start of optimal systemic therapy, there were no significant differences in overall survival or progression-free survival between patients randomized to receive locoregional therapy and those who did not receive the locoregional treatment.

Although patients who did not receive locoregional treatment had a 150% higher rate of local recurrence/progression, health-related quality of life (HRQOL) was actually worse at 18 months among the patients who underwent locoregional therapy. There were no HRQOL differences at 6 months, 12 months, or 30 months of follow-up.

Seema A. Khan, MD, of Northwestern University, Chicago, reported these results during a plenary session broadcast as a part of the American Society of Clinical Oncology virtual scientific program.

“There is no hint here of an advantage in terms of survival with the use of early locoregional therapy for the primary site,” Dr. Khan said.

Although neither the E2108 trial nor similar trials showed an overall survival advantage for locoregional therapy, as many as 20% of patients who are treated with systemic therapy alone may need locoregional therapy with surgery and/or radiation at some point for palliation or progression, said invited discussant Julia R. White, MD, professor of radiation oncology at the Ohio State University, Columbus.

“Locoregional therapy should be reserved for these patients that become symptomatic or progress locally. There may be a role for routine locoregional therapy for de novo oligometastatic breast cancer in combination with systemic therapy plus ablative therapy” to secure long-term remission or cure, questions that are being addressed in ongoing clinical trials, Dr. White said.

Past data

An estimated 6% of newly diagnosed breast cancer patients present with stage IV disease and an intact primary tumor.

The rationale for locoregional therapy of the primary tumor in patients with metastatic disease is based on retrospective data suggesting a survival advantage. However, the studies were biased because of younger patient populations with small tumors, a higher proportion of estrogen receptor–positive disease, and a generally lower metastatic burden than that seen in the E2108 population, according to Dr. Khan.

She went on to cite two randomized trials with differing outcomes. One trial showed no survival advantage with locoregional therapy at 2 years (Lancet Oncol. 2015 Oct;16[13]:1380-8). The other showed an improvement in survival with locoregional therapy at 5 years (Ann Surg Oncol. 2018 Oct;25[11]:3141-9).

E2108 details

In the E2108 trial, patients first received optimal systemic therapy based on individual patient and disease features. Patients who had no disease progression or distant disease for at least 4-8 months of therapy were then randomized to additional therapy.

In one randomized arm, patients received continued systemic therapy alone. The other arm received early local therapy, which included complete tumor resection with free surgical margins and postoperative radiotherapy according to the standard of care.

A total of 390 patients were registered, and 256 went on to randomization. Of those subjects, 131 were randomized to the continued systemic therapy arm and 125 to the early local therapy arm. All patients in each arm were included in the efficacy analysis.

In all, 59.6% of randomized patients had hormone receptor–positive/HER2-negative disease, 8.2% had triple-negative disease, and 32.2% had HER2-positive disease. Metastases included bone-only disease in 37.9% of patients, visceral-only disease in 24.2%, and 40.9% in both sites.

Among the patients randomized to early local therapy, 14 did not have surgery for personal, clinical, or insurance reasons. Of the 109 who went on to surgery, 87 had clear surgical margins, and 74 received locoregional radiation therapy.


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