DD adjuvant CT is standard of care in high-risk early BC pts. However, the role of DD CT in HER2+ BC pts remains uncertain, particularly when T is administered. In this exploratory analysis of the GIM2 trial (Del Mastro et al, Lancet 2015), we investigated the efficacy of DD CT in the subgroup of HER2+ BC pts with or without subsequent exposure to T.
Using a 2x2 factorial design, the GIM2 trial randomized node-positive early BC pts to receive 4 cycles of (fluorouracil)epirubicin/cyclophosphamide (F)EC every 2 (DD) or every 3 (standard interval [SI]) weeks followed by 4 cycles of DD or SI paclitaxel (P). The same number of cycles (4 (F)EC and 4 P) and doses (FEC 600/90/600 mg/m2, P 175 mg/m2) were used in all treatment arms. After the approval of adjuvant T, protocol was amended in April 2006 to mandate use of T for 1 year after CT completion in all HER2+ pts. The efficacy of DD CT in terms of disease-free survival (DFS) and overall survival (OS) was compared between HER2+ pts with or without subsequent exposure to T and those with HER2-negative /HER2-unknown (HER2-/ukn) status.
Out of 2,003 pts randomized to DD or SI CT in the GIM2 study, HER2 status was positive in 452 (22.6%) pts, negative in 1,243 (62.0%) and unknown in 308 (15.4%). Among 452 pts with HER2+ disease, T was administered to 132 (29.2%) pts. Overall median follow-up was 8.1 years (interquartile range: 7.0-9.3). There was no significant interaction between T therapy and the effect of DD CT, (pinteraction=0.603 for DFS and pinteraction=0.776 for OS); however, among pts treated with T, the effect of DD CT appeared to be smaller as shown in the table.
% 7-year DFS SI % 7-year DFS DD HR (95% CI) HER2+ NO trastuzumab 67.0 72.1 0.84 (0.56-1.24) HER2+ with trastuzumab 72.3 70.4 0.80 (0.40-1.59) HER2-/ukn 73.3 79.9 0.72 (0.59-0.88) % 7-year OS SI % 7-year OS DD HER2+ NO trastuzumab 78.6 85.2 0.67 (0.39-1.16) HER2+ with trastuzumab 86.1 84.9 1.04 (0.36-3.00) HER2-/ukn 85.3 90.9 0.64 (0.49-0.84)
In HER2+ early BC pts, DD adjuvant CT appears to have a role only in pts without subsequent exposure to T.
NCT00433420.
GIM (Gruppo Italiano Mammella) Study Group.
Bristol-Myers Squibb, Pharmacia, and Dompè Biotec.
M. Lambertini: Advisory role: Teva; Speakers’ honoraria: Theramex. E. de Azambuja: Honoraria: Roche-Genentech; Research grants: Roche-Genentech (to the institution); Travel grants: Roche-Genentech, GlaxoSmithKline outside the submitted work. L. Del Mastro: Personal fees: Novartis Pharma AG, Roche-Genentech, Ipsen, AstraZeneca, Takeda, Eli Lilly outside the submitted work. All other authors have declared no conflicts of interest.