Intensified Total Neoadjuvant Therapy in Patients With Locally Advanced Rectal Cancer: Long-term Results of a Prospective Phase II Study.

AIMS: To analyze the long-term results of a prospective phase II trial testing intensified total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC).

MATERIALS AND

METHODS

Patients with histologically confirmed LARC adenocarcinoma were enrolled. Intensified TNT consisted of targeted agent (bevacizumab or panitumumab/cetuximab) plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified (oxaliplatin and 5-fluorouracil) chemoradiotherapy (CRT) and surgical resection. Follow-up data were collected for all patients included in the trial. Survival outcomes were calculated using the Kaplan-Meier method and curves were compared by the log-rank test.

RESULTS

Between October 2015 and September 2019, 28 LARC patients were enrolled. Follow-up data were available for all included patients. In total, 11 (39.3%) patients had a complete response (CR). At 6.3 years (median follow-up), 5-year overall survival (OS) and DFS were 74.6% and 57.1%, respectively. Five-year OS was 80.8% for CR patients and 70.1% for no-CR patients (p-value 0.07). Those patients with CR after TNT treatment had a 5-year DFS of 81.8% versus 41.2% for those with no CR (p-value 0.015).

CONCLUSION

The addition of a targeted agent to induction FOLFOXIRI and oxaliplatin to 5-fluorouracil-based CRT, with the doses and intensities used in this study, resulted in high CR rates. Patients who achieve a CR demonstrate superior DFS compared to patients without CR. Intensified TNT may have the potential to increase survival outcomes. Further research on TNT strategies in LARC is encouraged.