Abstract 424P
Background
Multimodality treatment has been the standard of care for LARC for the past decades, but the optimal sequencing strategy is a matter of debate. The addition of induction or consolidation chemotherapy (CT) to standard neoadjuvant CRT may increase tumour downstaging and anticipate systemic treatment of micrometastatic disease. However, several randomized clinical trials (RCT) have evaluated the role of TNT vs. CRT with inconsistent results, with the small size of most studies possibly leading to an underestimation of the effect of the TNT strategy. We therefore performed a systematic review and MA of RCTs in this setting to synthesize available data and help decision-making.
Methods
A systematic search was performed through MEDLINE, EMBASE, ESMO and ASCO meeting abstracts up to May 2020 to identify RCTs for neoadjuvant treatment comparing standard neoadjuvant radiotherapy vs. TNT (induction or consolidation CT + RT) followed by surgery. Studies were reviewed by two authors and discrepancies were resolved by consensus or by a third author. Data including pathological complete response (pCR) rate, disease-free survival (DFS), overall survival (OS) and adverse effects (AEs) were extracted. The primary endpoint was the pCR rate. A MA with fixed and random effect models comparing the different regimens with direct comparisons was conducted.
Results
Eight RCTs including 2175 patients with stage II-III LARC were identified. Overall, the pooled analysis demonstrated that TNT significantly improved pCR rate (OR= 0.52, 95% CI 0.38-0.71, p < 0.001) and 3 year-DFS (HR=0.73, 95% CI 0.62-0.87, p=0.01). No difference was found in 3 year-OS among treatment strategies (HR=0.89, 95% CI 0.71-1.10). When Short Course RT and CRT trials were analysed separately, a statistically significant benefit in pCR ( HR=0.51,p=0.003; HR 0.7, P=0.02 respectively) and 3 y-DFS rates (HR= 0.75, p=0.003;HR=0.82, P=0.03) was maintained, favouring the TNT strategy. Grade 3-4 AEs were not significantly different in both strategies (OR=1.1; P=0.33). No significant heterogeneity was found among RCTs.
Conclusions
The results of direct MA suggest that TNT vs. CRT improves pCR and 3-y DFS rates for patients with LARC. TNT may become a new standard of care in LARC, although longer follow-up is needed to properly assess its impact on OS.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M.C. Riesco Martínez: Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Bayer; Travel/Accommodation/Expenses: Servier. C. Grávalos: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck; Advisory/Consultancy: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Servier; Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Travel/Accommodation/Expenses: Pierre-Fabre. P. Espinosa-Olarte: Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Pfizer. A. Modrego-Sánchez: Travel/Accommodation/Expenses: Novartis. R. Garcia-Carbonero: Advisory/Consultancy, Speaker Bureau/Expert testimony: AAA; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Speaker Bureau/Expert testimony: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Servier; Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck. All other authors have declared no conflicts of interest.