• Oncology Clinical Trials
• Breast Cancer

• Oncology Clinical Trials
• Breast Cancer
• Oncology

Stefanie Noeding, MD, Gynecologic-Oncology Practice, Hannover, Germany, presented data from the first interim safety analysis of the Study of Nab-Paclitaxel in High-Risk Early Breast Cancer [GAIN2; NCT01690702], demonstrating acceptable initial toxicity profiles.

According to Dr Noeding, owing to acute and cumulative toxicities, combination chemotherapy requires compromises in drug dosage and treatment intervals. The sequential use of monotherapies, however, allows for the use of high doses of single agents and dose-dense treatment intervals, and such regimens have been very effective in cases of early breast cancer with high risk of recurrence [Moebus V et al. J Clin Oncol. 2010].

Compared with the solvent-based taxanes, paclitaxel and docetaxel, nab-paclitaxel (nP) provides a more favorable toxicity profile and a higher efficacy and might therefore be preferable in an intense dose-dense regimen [Ibrahim NK et al. J Clin Oncol. 2005].

Consequently, the GAIN2 study was an adjuvant phase 3 trial in patients with high-risk early breast cancer that was designed to compare a predefined intense dose-dense adjuvant treatment (epirubicin followed by nP followed by cyclophosphamide [ddEnPC]) with a dose-dense tailored therapy. In the study, single doses are adjusted depending on individual hematologic and nonhematologic toxicities (dose-dense and dose-tailored epirubicin or cyclophosphamide followed by dose-dense and dose-tailored docetaxel [dtEC-dtD]).

This multicenter, prospective, randomized, open-label phase 3 trial randomized 2886 patients 1:1 to receive ddEnPC or dtEC-dtD. Inclusion criteria included women aged 18 to 65 years with pathologically confirmed high-risk breast cancer, defined as HER2-positive or triple-negative tumors irrespective of nodal status; luminal B-like tumors with Ki67 proliferation marker levels > 20%; or luminal A-like tumors with Ki67 ≤ 20% and ≥ 4 involved lymph nodes. The primary end point was the invasive disease-free survival in patients with primary node-positive or high-risk node-negative breast cancer.

This first safety analysis comprises data from the first 200 patients who completed chemotherapy. With respect to hematologic adverse events (AEs), the rates of febrile neutropenia grade 3 to 4 (14.1% vs 5.0%; P = .031) and thrombocytopenia grade 3 to 4 (14.1% vs 5.0%; P = .031) were significantly increased in the ddEnPC arm. Similarly, with respect to nonhematologic AEs, significantly more patients in the ddEnPC arm developed anorexia grade 1 to 4 (28.3% vs 13.9%; P = .015). There was no significant difference between the 2 treatment arms with respect to AEs of special interest (cranial nerve palsies, anaphylaxis, or macular edema).

According to Dr Noeding, more patients in the ddEnPC arm required dose reductions because of hematologic toxicities (28% vs 11%; P = .002). Dose escalation to the maximum tolerated dose was possible in half of the patients receiving dtEC-dtD, whereas 7% of patients required dose reduction in the fourth cycle of docetaxel.

Because of acceptable toxicity profiles in both arms in these first 200 patients, the study will proceed as originally planned. An additional safety analysis will be performed after 900 patients have completed chemotherapy, and efficacy analyses are planned 60 months after the end of accrual.

• © 2014 MD Conference Express®