Advanced breast cancer: Locoregional therapy does not improve OS

E2108 trial results showed that local therapy did not improve overall survival (OS) when compared with optimal systemic therapy alone. Added locoregional therapy also failed to improve 3-year progression-free survival (PFS).

Results from the long-awaited E2108 trial showed that local therapy did not improve overall survival (OS) when compared with optimal systemic therapy alone. The addition of locoregional therapy also failed to improve 3-year progression-free survival (PFS). However, recurrence or progression was significantly higher in the systemic arm alone.

With a median follow-up of 59 months, Prof. Seema Ahsan Khan (Feinberg School of Medicine, University of Chicago, USA) presented the final follow-up data [1]. There has been a paucity of data about whether surgery and radiation to a breast tumor (local therapy) can prolong OS compared with systemic treatment alone. The goal of E2108 was to determine whether surgery and radiation should become routine practice for patients with stage IV breast cancer.

In total, 390 women with stage IV breast cancer were enrolled and received the optimal systemic treatment based on their tumor biomarker status and their metastatic profile. Of those whose disease responded to initial systemic therapy, 256 women were randomized to either receive continued systemic therapy or to receive surgery and radiation prior to continuing systemic therapy.

With 5 years follow-up, it was evident that there was no OS advantage for local therapy versus systemic therapy alone (68.4% vs 67.9%; HR 1.09; 90% CI 0.80-1.49; P=0.63). Furthermore, locoregional therapy did not improve 3-year PFS (P=0.40). In favor of local therapy, however, recurrence or progression was significantly higher in the systemic arm alone (25.6% vs 10.2%; P=0.003). Patient-reported quality of life, as measured by the FACT-B Trial Outcome Index to score depression, anxiety, and well-being, did not show any advantage for the locoregional therapy arm of the trial.

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

Prof. Khan concluded: "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."

Sources:
1. Khan SA, 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). ASCO Virtual Meeting, 29-31 May 2020, Abstract LBA2.
2. Badwe R, et al. Locoregional treatment versus no treatment of the primary tumor in metastatic breast cancer: an open-label randomized controlled trial. Lancet Oncol. 2015;16(13):1380‐1388.

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