Primary surgery in patients with de novo stage IV BC; finalizing the protocol MF07-01 randomized clinical trial

Abstract

Background. The MF07-01 trial is a multicenter randomized study comparing locoregional treatment (LRT) followed by systemic therapy (ST) with ST alone in de novo Stage IV breast cancer (BC) patients.

Aim: To evaluate and finalize the survival data of LRT in patients with the diagnosis of de novo Stage IV BC.

Methods. At initial diagnosis, patients were randomized 1:1 to either the LRT or ST group. All the patients were given ST either immediately after randomization or after surgical resection of the intact primary tumor. Continuous and categorical variable differences between LRT and ST groups were analyzed using t-test and Chi-square test, respectively. Overall survival (OS) and 5-year survival rates were compared using Kaplan-Meier log-rank tests. Univariate and multivariate Cox models were used to estimate hazard ratios, and logistic regession model used to estimate odds ratio.

Results. During more than 10 years follow-up, 23% of patients in LRT group and 8% of patients in ST group were alive. Median survival was 46 months for LRT (n=134) and 35 months for ST (n=131) [HR:0.71, 95%CI;0.59-0.86, p=0.0004]. Solitary bone metastasis patients’ median survival was 14 months longer in LRT group comparing ST group [HR:0.55, 95%CI; 0.35-0.86, p=0.008]; 16% of solitary bone metastasis patients in the LRT group were alive, but all patients died in the ST group. Patients younger than 55 lived longer compared the patients older than 55 [HR:0.67, 95%CI; 0.52-0.87, p=0.002], and 26% of hormone receptor positive patients were still alive in the LRT group comparing 10% in the ST group [HR:0.71, 95%CI; 0.58-0.88, p=0.002]. Regarding the patients who lived at least 5 years since randomization, LRT (p=0.003), hormone receptor positivity (p=0.004), Triple negative status (p=0.02), hormonotherapy (p=0.0001), bisphosphonates usage (p=0.03), and 2 or more organ metastases (p=0.004) were associated with OS in univariant analyses. However, in the multivariate model with significant baseline and clinical characteristics only LRT [OR= 1.58, p=0.03] was found to be significantly related with over 5 years of survival.

Conclusion. In the current analysis, patients at the diagnosis of de novo stage IV BC who underwent LRT followed by ST had a 58% higher chance to live at least 5 years compared to the patients who received only ST. Longer follow-up of the study discloses that LRT should be presented to patients when discussing treatment options.