Induction Chemotherapy and Toripalimab for Larynx Preservation in Resectable Locally Advanced Laryngeal/Hypopharyngeal Carcinoma: Preliminary Results of INSIGHT Study.

PURPOSE/OBJECTIVE(S): Previous studies have demonstrated excellent pathological response of induction PD-1 inhibitor with chemotherapy for locally advanced head and neck cancer. To our knowledge, there is scarce evidence on induction chemotherapy (ICT) and PD-1 inhibitor in organ preservation for patients (pts) with laryngeal/hypopharyngeal carcinoma. Hence, the aim of this study is to evaluate the efficacy and toxicities of ICT and PD-1inhibitor (Toripalimab) followed by radiotherapy or surgery, for pts with resectable locally advanced laryngeal/hypopharyngeal carcinoma.

MATERIALS/METHODS: This isa single-arm phase II study. Pts with histopathologic confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and ECOG PS 0-1 were eligible. Three cycles of ICT (paclitaxel 175 mg/m d1, cisplatin 25 mg/m d1-3) combined with PD-1 inhibitor (Toripalimab 240 mg d0) were given. Response assessment (RECIST 1.1) was performed post-ICT. Patients with complete response (CR)/partial response (PR) of primary tumor received concurrent chemoradiation, followed by maintenance therapy of Toripalimab for eight cycles. Otherwise, patients were referred to surgery, followed by adjuvant radiation (RT)/chemoradiation (CRT), and then maintenance therapy of Toripalimab. The primary endpoint is larynx-preservation (LP) rate at 3 months post-RT. Forty-two patients were planned. Based on a two-stage Fleming design (one-sided α:10%, power: 80%), if at least 22 patients attained LP of the first 27 patients in stage I or at least thirty-two pts attained LP of the 42 patients at the end of stage II, the null hypothesis would be rejected. The cohort would enroll 15 more pts in stage II if 19-21 pts in stage I observed LP, and the study would be terminated if the number of pts with LP were less than 18 in stage I.

RESULTS: A total of 27 pts were enrolled. By the cut-off date Feb 8, 2023, all reached at least 3 months of follow-up post-RT. Median age was 63 (53-74) years with 92.6% male. Hypopharyngeal cancer accounted for 66.7%. There were 74.1% who were T3 to T4, and 77.7% were N2 to N3. Six cases had primary invasion of esophagus and five pts underwent pretreatment tracheostomy. ORR of ICT was 85.2%. Afterward, 21 pts were treated with concurrent CRT, while 6 pts received surgery of primary tumor. At 3 months post-RT, 23 pts attained organ preservation and the LP rate was 85.2%. With a median follow-up of 13.5 months, 1-year OS rate, PFS rate and LP survival rate was 83.1%, 79.5% and 79.4%, respectively. During ICT, 22.2% of pts experienced grade 3-4 treatment-related AEs (TRAEs). The most common grade 3-4 TRAEs were nausea and neutrophil count decreased.

CONCLUSION: The primary endpoint LP rate was met. In this cohort of extensive locally advanced laryngeal/hypopharyngeal carcinoma, ICT and Toripalimab followed by radiotherapy or surgery resulted in satisfactory short-term LP rate and encouraging survival.