In the final analysis of a phase 3 trial, the use of dose-dense adjuvant chemotherapy improved disease-free survival (DFS) and overall survival (OS) in patients with early-stage breast cancer, when compared to the standard schedule.

This abstract was presented on Saturday, September 10, 2022, at the European Society for Medical Oncology Congress in Paris, France, by first author, Lucia Del Mastro, MD, Internal Medicine Department, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

This open-label, phase 3 trial enrolled 2091 patients with node-positive breast cancer, randomized on a 1:1:1:1 basis to receive either a dose-dense schedule of epirubicin-cyclophosphamide and paclitaxel, a dose-dense schedule of fluorouracil and epirubicin-cyclophosphamide and paclitaxel, a standard schedule of epirubicin-cyclophosphamide and paclitaxel, or a standard schedule of fluorouracil and epirubicin-cyclophosphamide and paclitaxel. The primary end point was DFS, comparing fluorouracil and epirubicin-cyclophosphamide and paclitaxel, and epirubicin-cyclophosphamide and paclitaxel, and the dose dense schedule vs the standard-interval schedule. Secondary endpoints include OS and safety.

It has been previously reported, in the primary analysis of this trial, that the DFS and OS were significantly improved in patients who received the dose dense schedule, and that the addition of fluorouracil provided no benefit.

At the median follow-up duration of 15.11 years, 34.2% of patients in the dose-dense arm experienced a DFS event, compared to 40.9% in the standard schedule arm. The 15-year DFS of the dose-dense arm was 61% (95% confidence interval [CI], 58 to 64), compared to 52% (95% CI, 49 to 56) in the standard schedule arm (hazard ratio [HR]: 0.77; 95% CI, 0.67 to 0.89; P < .001). In the dose-dense arm, 19.7% of patients experienced an OS event, compared to 25.4% in the standard schedule arm, and there was 15-year OS of 76% (95% CI, 73 to 79) compared to  69% (95% CI, 65 to 72) in the standard schedule arm (HR: 0.72; 95% CI, 0.60 to 0.86; P < .001). The addition of fluorouracil did not significantly improve the DFS (HR: 1.12; 95% CI, 0.98 to 1.29) or OS (HR: 1.13, 95% CI, 0.94 to 1.36; P = .18)

For those patients who were hormone receptor-positive (n = 1611), the 15-year OS was 76% (95%CI, 72 to 79) and 71% (95% CI, 67 to 74) in those treated with the dose-dense scheduled and the standard schedule, respectively. For those patients who were hormone receptor-negative (n = 335), the 15-year OS was 76% (95% CI, 69 to 83) and 63% (95% CI, 55 to 71), respectively.

There were 4 cases of myelodysplasia/leukemia reported.

Dr Del Mastro and colleagues concluded, “The [dose dense regimen] should be considered the standard adjuvant schedule for node-positive breast cancer patients.”

Source:

Del Mastro L, Poggio F, Blondeaux E, et al. “Dose-dense adjuvant chemotherapy in early-stage breast cancer patients: End-of-study results from a randomised, phase III trial of the Gruppo Italiano Mammella (GIM).” Presented at European Society for Medical Oncology Congress; September 9-13, 2022. Paris, France.