Final, 10-Year Follow-up of Phase III Trial on Adding Gemcitabine to Adjuvant Therapy in Breast Cancer
The final, 10-year follow-up of the ‘all comers’ tAnGo trial, reported by Earl et al in The Lancet Oncology, continued to show no overall benefit of adding gemcitabine to adjuvant therapy in women with early-stage breast cancer. The trial, initiated in 2001, included patients irrespective of hormone receptor and nodal status and was performed before the use of adjuvant trastuzumab (Herceptin) for HER2-positive disease became standard.
Study Details
In the open-label phase III trial, 3,152 women with newly diagnosed disease from sites in the UK and Ireland were randomized between August 2001 and November 2004 to receive adjuvant epirubicin, cyclophosphamide, and paclitaxel with (n = 1,576) or without gemcitabine (n = 1,576). Stratification factors included age, radiotherapy intent, nodal status, and estrogen receptor and HER2 status. The primary endpoint was disease-free survival on intent-to-treat analysis. Preliminary efficacy results reported in 2008 showed no benefit of adding gemcitabine on disease-free or overall survival.
Final Outcomes
At the protocol-specified final analysis, with a median follow-up 10 years, disease-free survival was 65% in the gemcitabine group vs 65% in the control group; median disease-free survival was not reached in either group (adjusted hazard ratio [HR] = 0.97, P = .64). There was no significant difference between the groups in overall survival (adjusted HR = 1.02, adjusted P = .81). Median overall survival was not reached in either group; 2-, 5-, and 10-year rates were 93% vs 94%, 82% vs 82%, and 70% vs71%, respectively.
Grade 3 and 4 toxicities were those expected in both groups. The most common effects were neutropenia (34% vs 26%), myalgia/arthralgia (13% vs 12%), fatigue (13% vs 10%), infection (13% vs 9%), vomiting (9% vs 7%), and nausea (8% vs 7%).
The investigators concluded: “The addition of gemcitabine to anthracycline and taxane-based adjuvant chemotherapy at this dose and schedule confers no therapeutic advantage in terms of disease-free survival in early breast cancer, although it can cause increased toxicity. Therefore, gemcitabine has not been added to standard adjuvant chemotherapy in breast cancer for any subgroup.”
The study was funded by Cancer Research UK, Eli Lilly, Bristol-Myers Squibb, and Pfizer.
Helena Earl, MBBS, of the University of Cambridge, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
