Overall Survival Not Increased With Locoregional Therapy in Advanced Breast Cancer

Seema A. Khan, MD

Performing surgery and radiation to stage IV breast tumors did not improve overall survival (OS) compared with systemic treatment alone, according to data from the ECOG-ACRIN E2108 trial presented ahead of the 2020 ASCO Virtual Scientific Program.¹

At a median follow-up of 59 months, investigators led by Seema A. Khan, MD, found no significant difference in OS between optimal systemic therapy plus locoregional therapy compared with optimal systemic therapy alone (68.4% vs 67.9%; HR, 1.09; 90% CI, 0.80-1.49; P = .63). The addition of locoregional therapy also failed to improve 3-year progression-free survival (P = .40).

However, locoregional recurrence or progression was significantly higher in the systemic arm alone (25.6% vs 10.2%; P = .003).

“Based on the results of our study, women who present with a new diagnosis of breast cancer already in stage IV should not be offered surgery and radiation for the primary breast tumor with the expectation of a survival benefit,” Khan, the Bluhm Family Professor of Cancer Research and professor of surgery (breast surgery) at Northwestern University’s Feinberg School of Medicine, said in a news release.² “When making these decisions, it is important to focus energy and resources on proven therapies that can prolong life.”

Traditionally, physicians have believed local therapy would not provide any additional survival benefit beyond systemic treatment could offer once metastases had occurred. Some studies suggested that surgery to remove the tumor would be beneficial, but these findings were criticized because women receiving surgery tended to be younger, healthier, and have less severe disease.

Investigators in the phase 3 ECOG-ACRIN E2108 trial (NCT01242800) recruited 390 women from February 2011 through July 2015 to determine whether the addition of locoregional treatment improved OS. Overall, 256 eligible patients were assigned to systemic therapy based on patient and tumor characteristics. Those who did not progress during 4 to 8 months of treatment were then assigned to continue systemic therapy alone (n = 131) or plus locoregional treatment with surgery and radiation for the intact primary tumor (n = 125).

Khan said these data are similar to findings from a study of 716 women with de-novo metastatic breast cancer treated at Tata Memorial Centre from February 2005 to January 2013 (NCT00193778). A total of 173 women were assigned to locoregional treatment while 177 received only systemic treatment.³

At a median follow-up of 23 months, the median OS was 19.2 months (95% CI, 15.98-22.46) in the locoregional treatment group compared with 20.5 months (95% CI, 16.96-23.98) in the systemic treatment group (HR, 1.04; 95% CI, 0.81-1.34; P = .79). Two-year OS also showed no advantage for locoregional treatment (41.9% vs 43.0%).

“When combined with the results of an earlier trial in Mumbai, India, these results tip the scales against the possibility that local therapy to the breast tumor will help women live longer,” Khan said. “The Indian trial had a similar design to E2108, and also showed similar results between the 2 treatment groups.”

Investigators in ECOG-ACRIN E2108 evaluated health-related quality of life using the FACT-B Trial Outcome Index, which measures factors such as depression, anxiety, and well-being. Results showed that no quality-of-life advantage was associated with locoregional therapy.

“This result was a little surprising since one of the reasons for considering surgery and radiation is the idea that growth of the tumor will impair quality of life,” Khan said. “Instead, we find that the adverse effects of surgery and radiation appear to balance out the gains in quality of life that were achieved with better control of the primary tumor.”

_References:

_{1. 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. 2020;38(suppl; abstr LBA2). doi:10.1200/JCO.2020.38.18_suppl.LBA2}

_{2. ECOG-ACRIN Cancer Research Group. Surgery and radiation do not extend survival in newly diagnosed metastatic breast cancer. Published May 28, 2020. https://bit.ly/3ddC2M3. Accessed May 28, 2020.}

_{3. Badwe R, Hawaldar R, Nair N, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol. 2015;16(13):1380‐1388. doi:10.1016/S1470-2045(15)00135-7}