It appears to be safe to hold the anthracycline in patients with HER2-negative early breast cancer who are at intermediate-to-high genomic risk, results of a large randomized trial suggest.
Among both pre- and postmenopausal women with pathologic stage T1 to T4c with positive nodes or node-negative but high-risk early breast cancer, there were no significant differences in 5-year outcomes for patients treated with six cycles of docetaxel and cyclophosphamide (TC) or four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (EC-T), reported Ulrike Nitz, MD, from the West German Study Group in Mönchengladbach, Germany, and her colleagues in the.
Disease-free survival (DFS, the primary endpoint), distant recurrence-free interval (dRFI), and overall survival (OS) “were excellent and virtually identical in patients who received the anthracycline-containing or the anthracycline-free regimen. Subgroups that benefited from the anthracycline-containing regimen were not identified by interaction analysis, although a potentially clinically relevant benefit in particular (e.g., high-risk) subgroups cannot be ruled out,” they wrote. The report is in.
The investigators noted that anthracyclines are associated with increased risk for cardiac disease and hematologic malignancies, prompting investigators in other trials to consider anthracycline-free regimens.
“As the number of long-term survivors, elderly patients, and patients with preexisting cardiac risk factors increases, the toxicity profile becomes a more important discriminator in adjuvant treatment selection,” they wrote.
The investigators enrolled and randomized 2,449 women (median age 55, range 25-77 years) who had histologically confirmed, unilateral primary invasive breast cancer, adequate surgical treatment, and no evidence of metastatic disease. The patients all had HER2-negative disease, pT1 to pT4c, known hormone receptor status, and either pN+ or pN0 with one or more risk factors.
The intention-to-treat analysis included 1,227 patients assigned to EC-T and 1,222 assigned to TC in the efficacy population, and 1,167 and 1,178 patients, respectively, in the safety population.
After a median follow-up of 60 months, the 5-year DFS rate in the TC-treated group was 89.6%, compared with 89.9% in the EC-T–treated group. The estimated 5-year dRFI rates were 94.1% vs. 93.4%, and the estimated 5-year OS rates were 94.7% vs. 94.5%, respectively. None of the comparisons were statistically significant.
There were five treatment-related deaths in the TC arm, (one each from urosepsis, Streptococcus septicemia, peritonitis/diverticulitis, Staphylococcus epidermidis septicemia, and pulmonary embolism), and one in the EC-T arm (from septicemia).
In an interim safety analysis, the rate of febrile neutropenia was 6.1% in the TC arm and 3.9% in the EC-T arm, leading to a recommendation for “generous” prophylaxis with granulocyte-colony stimulating factor, and ciprofloxacine for patients with a history of diverticulitis or chronic infectious GI disease, or expected duration of neutropenia greater than 1 week.
Rates of grade 3 or 4 leukopenia, neutropenia, nausea, vomiting, peripheral polyneuropathy, hand-foot syndrome, mucositis/stomatitis, arthralgia, myalgia, and fatigue were significantly higher among patients treated with EC-T. There were numerically more grade 3-4 infections and febrile neutropenia within the TC arm, but this trend did not reach statistical significance.
The investigators noted that the results of their trial provide the strongest evidence for patients with pathologic NO or N1 disease, and that the trial did not examine the question of dose-dense chemotherapy in patients with high-risk early breast cancer.
Genomic Health, Sanofi, and Amgen supported the study. Dr. Nitz and multiple coauthors disclosed financial relationships with these companies and others.
SOURCE: Nitz U et al. J Clin Oncol. 2019 Feb 20. .