De-escalate surgery of primary lesions after neoadjuvant immune-combination therapy in locally advanced oral squamous cell carcinoma: The 5-year survival results of two single-arm trials.

Abstract

e18121 Background: Neoadjuvant immune-combination therapy (NAIT) followed by surgery and adjuvant therapy has been widely studied for resectable locally advanced oral squamous cell carcinoma (LAOSCC). Given the excellent short-term tumor shrinkage effect of NAIT, de-escalate surgery has attracted increasing attention. However, there are few long-term prognostic results corresponding to de-escalate surgery after NAIT in LAOSCC. Methods: We conducted a retrospective analysis of two single-arm NAIT trials, including neoadjuvant immunotarget therapy (NAITT) trial (NCT04393506) and neoadjuvant immunochemotherapy (NAICT) trial (NCT04473716) in LAOSCC patients. 5-year survival analysis was performed including overall survival (OS) and disease-free survival (DFS). Primary tumors were assessed for the percentage of residual viable tumor that was identified on HE staining, and tumor with no more than 10% viable tumor cell was considered as major pathological response (MPR). To determine whether NAIT can improve the long-term prognosis of LAOSCC patients, we compared the 5-year OS and DFS with the neoadjuvant chemotherapy (NACT) of TPF group and the conventional standard treatment (CST) group (surgery followed by adjuvant therapy) (from the previous trial of NCT01542931), using propensity score matching (PSM) based on gender, age, clinical T stage to reduce confounding bias. Additionally, we analyzed the proportion of de-escalate surgery of primary lesions with exemption of free flap reconstruction in the NAIT group, and their long-term prognostic outcomes. Results: From April 2020 to April 2021, 40 LAOSCC patients in two trials received NAIT and radical surgery. The MPR rate of NAIT was 50%. In the patients archived MPR, the 5-year OS and DFS rate was 100% and 95%, in the non-MPR patients, the 5-year OS and DFS rate was 80% and 70%. The patients in the NACT group and CST group were collected from the NCT01542931 trial, following a 1:1:1 PSM adjustment, each group consisted of 40 patients. The patients in the NAIT group had improved 5-year OS compared with the NACT and CST groups (85% vs. 67.5% vs. 57.5%, p=0.024) as well as 5-year DFS (75% vs. 65% vs. 55%, p=0.170). In the NAIT group, four patients achieved de-escalate surgery, obviating free flap reconstruction, none of them experienced surgical complications, and other four patients refused adjuvant radiotherapy because of good pathological response to NAIT; during the follow-up period, no local recurrence or distant metastasis occurred in these patients. Conclusions: NAIT followed by radical surgery could improve the long-term prognosis of LAOSCC patients. The reduction of tumor burden induced by NAIT might translate into de-escalate surgery with reducing free flap reconstruction or exemption of adjuvant radiotherapy without compromising their prognosis. Clinical trial information: NCT04393506 , NCT04473716 .