Early breast cancer meta-analysis

EBCTCG Meta-Analysis: Dose-Intense Chemotherapy Delays Recurrence and Improves Survival in Early Breast Cancer

The 2017 San Antonio Breast Cancer Symposium (SABCS) was held from 5 to 9 December in San Antonio, Texas, marking the 40th anniversary for this important breast cancer conference. As in past years, the main mission of the conference was to provide participants with an update on translational and clinical research in breast cancer over the last year. Over the next several weeks, prIME LINES™ will be highlighting some of the interesting and potentially practice-changing findings presented at the 2017 meeting.

At the first oral abstract session, Richard Gray, MSc (University of Oxford, Oxford, United Kingdom), presented results from a meta-analysis on behalf of the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), which included more than 34,000 patients from 25 randomized trials, and examined the impact of the dose intensity of chemotherapy on outcomes in women with early-stage breast cancer. It was shown previously that adjuvant anthracycline- and taxane-based chemotherapy reduces the risk of breast cancer mortality by about one third, and these regimens are current standard of care for early breast cancer. Several pivotal studies previously demonstrated that dose intensification by either reducing the interval between treatment cycles or giving drugs sequentially may further improve outcomes compared to standard 3-weekly regimens. This EBCTCG meta-analysis examined results from trials of chemotherapy given every 2 weeks (dose-dense) versus every 3 weeks, trials comparing sequential versus concurrent chemotherapy (both given every 3 weeks), and trials comparing 2-weekly sequential regimens to 3-weekly concurrent regimens.

In the trials comparing dose-dense 2-weekly chemotherapy versus 3-weekly chemotherapy, patients receiving dose-dense chemotherapy had a 17% reduction in risk of disease recurrence (RR 0.83, P = .00004) and a 14% reduction in the risk of breast cancer death within 10 years (RR 0.86, P =.004) compared to women receiving chemotherapy every 3 weeks.

Similarly, in the trials comparing concurrent versus sequential administration (both 3-weekly), sequential dosing significantly reduced the risk of recurrence by 13% (RR 0.87, P = .0006) and the risk of breast cancer death by 11% (RR 0.89, P = .03) compared to concurrent chemotherapy. However, the dose intensification achieved with the sequential versus concurrent approach when both given 3-weekly was less than with 2-weekly dose-dense chemotherapy and resulted in smaller treatment effect. The biggest treatment effect was achieved in the trials comparing 2-weekly sequential chemotherapy to 3-weekly concurrent chemotherapy. In these trials, the reduction of risk of recurrence within 10 years was nearly 20% (RR 0.82, P = .0001) and the reduction of risk of death was similar (RR 0.82, P = .001).

In the pooled analysis of all 25 dose-dense and sequential trials, patients who received dose-intensified chemotherapy regimens had a 15% reduction in risk of breast cancer recurrence (RR 0.85, P<.00001) and a 13% reduction in the risk of breast cancer mortality (RR 0.87, P< .0001) within the 10 years.  At 10 years absolute recurrence rates were 4.4% lower, and mortality was 3.7% lower with dose-intensification regimens. Importantly, there was no significant increase in toxicity with the dose intensification. In addition, these results were seen in patients regardless of hormone-receptor status and other tumor or patient characteristics.

In his conclusion, Professor Gray called these results highly significant, highlighting the importance of small, incremental improvements in breast cancer mortality reduction for improving outcomes of patients with early breast cancer over the long-term. Using a dose-intensification approach with anthracyclines and taxanes results in a nearly 50% reduction in the risk for breast cancer death.