247P - Concurrent versus sequential adjuvant chemoradiotherapy in early-stage breast cancer: A systematic review and meta-analysis

Background

Adjuvant radiation therapy (RT) is standard-of-care following breast-conserving surgery in patients with early-stage breast cancer, while adjuvant chemotherapy is recommended for patients at higher risk of distant recurrence. Data on the ideal sequencing of both adjuvant treatment modalities is limited. Hence, we sought to investigate whether concurrent or sequential delivery of chemotherapy and RT provides superior oncologic outcomes.

Methods

PubMed, Embase, and Cochrane were systematically searched for randomized controlled trials (RCTs) comparing concurrent with sequential administration of adjuvant chemotherapy and RT. Outcomes of interest included locoregional recurrence (in-breast, contralateral breast, and nodal recurrence), distant recurrence, disease-free survival (DFS) and overall survival (OS). Statistical analyses employed random or fixed-effects models with 95% confidence intervals (CI).

Results

From 1,477 initially identified studies, four phase III RCTs with 3,835 patients were selected, of whom 1,932 (50.4%) received concurrent chemotherapy and RT. Locoregional recurrence was lower in patients undergoing concurrent chemoradiation compared to sequentially delivered therapy (OR 0.58; 95% CI 0.43-0.78; P < 0.01). Subgroup analysis excluding T4 tumors yielded similar results. No differences between the sequencing approaches were observed in contralateral breast recurrence (OR 0.78; 95% CI 0.44-1.39; P = 0.46), distant recurrence (OR 1.04; 95% CI 0.82-1.32; P = 0.76), OS (HR 1.02; 95% CI 0.87-1.19; P = 0.82) or DFS (HR 1.00; 95% CI 0.87-1.14; P = 0.95). Concurrent therapy was associated with moderate or severe breast subcutaneous fibrosis (OR 2.38; 95% CI 1.15-4.91; P <0.01; I2 = 33%) and telangiectasia (OR 1.96; 95% CI 1.00-3.44; P = 0.05), while no statistically significant difference was observed regarding lymphedema and severe skin toxicity.

Conclusions

Adjuvant therapy delivered via concurrent chemoradiation improved locoregional control at a cost of increased breast fibrosis and telangectasia. No differences were observed in DFS or OS. Further RCTs using more modern systemic and radiation therapy regimens are warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.