Neoadjuvant toripalimab combined with gemcitabine and cisplatin in resectable locally advanced head and neck squamous cell carcinoma (NeoTGP01): An open label, single-arm, phase Ib clinical trial

Abstract

Background Neoadjuvant programmed death receptor-1 (PD-1) inhibitors have drawn increasing attention in locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the safety and efficacy of gemcitabine and cisplatin (GP), combined with a PD-1 inhibitor, in patients with locally advanced HNSCC. Materials and methods A total of 23 eligible patients were administered two cycles of toripalimab and GP followed by surgical resection. The primary endpoints were safety, treatment-related adverse events (TRAEs), and non-operation delay rates. The secondary endpoints consisted of pathological complete response (pCR) rate, major pathological response (MPR) rate, objective response rate (ORR), and R0 resection rate. Results The incidence of TRAEs from grades 1 to 4 was 43.5%, 34.8%, 13.0%, and 8.7%, respectively. Grade 3/4 TRAEs included neutropenia, fatigue, hyperglycemia, nausea and vomiting, decreased appetite, rash, and diarrhea. No treatment-related surgical delay was observed. The radiographic response rates were 5.0% (CR), 40.0% (PR), and 55.0% (SD). The ORR reached 45.0%. Eighteen patients underwent successful surgical resection. The R0 resection rate was 100%. The pathological response rates were 16.7% (pCR), 27.8% (MPR, two of five near-pCR), 16.7% (PPR), and 38.8% (NPR). CD4, CD8, CD20, and CD38 expression in the tumors significantly increased after neoadjuvant chemotherapy. The increase in CD20 levels after neoadjuvant treatment in patients with pCR/MPR was significantly higher than in patients with PPR/NPR. Conclusion Triweekly neoadjuvant toripalimab-GP is feasible and achieves promising pCR and MPR rates in patients with resectable locally advanced HNSCC. Trial registration Chinese clinical trial registry, ChiCTR2100043743, Registered 27 Febrary 2021- Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=120570

Neoadjuvante Immuntherapie bei Kopf-Hals- Plattenepithelkarzinomen

“…Here, the reported complete response rates have increased from nivolumab (0%) 101 , nivolumab plus ipilimumab (7%) 102 , or 4% 104 to 10% in two reports combining immunotherapy with targeted therapy 111 112 . This increased further in the setting of combination with chemotherapy to 37.0% 114 , 30% 115 , 16.7% 116 , and 36.4% 117 , an assessment which is supported by a recent metanalysis of ORR comparing neoadjuvant immunotherapy to immunochemotherapy 126 .…”

“…Es gab keine Verzögerungen bei der Operation aufgrund unerwünschter neoadjuvanter Behandlungsnebenwirkungen. Über alle Kohorten hinweg lag das MPR bei 86 %, davon 67 % pathologisch vollständiges Ansprechen [116].…”

“…Grade 3 adverse events occurred in 13.0 % of patients and Grade 4 in 8.7 %, with no treatment-related delays of surgery. Of the patients, 44.4 % achieved major pathological response, including 16.7 % who achieved complete pathological response [116]. Another single-arm, single-center study with a mixed cohort of HNSCC investigated 2-3 cycles of pembrolizumab with cisplatin and paclitaxel in 22 patients.…”

Case report: Brain metastasis necrosis with immune checkpoint inhibitors plus chemotherapy for advanced non-small cell lung cancer

“…There could be some disagreements between radiographic and pathological evaluations, which may be frequently observed in perioperative immunotherapy. A recent study by Zhigang Liu et al reported that three patients were confirmed to achieve pCR after surgery, while only one patient achieved radiographic PR according to the response evaluation criteria in solid tumors (RECIST) (23). Lee JM, et al summarized the data of pathological and radiographic response of several neoadjuvant immunotherapy clinical trials of NSCLC, demonstrating large differences in results when the two methods of evaluation were compared (24).…”

“…A recent study by Zhigang Liu et al. reported that three patients were confirmed to achieve pCR after surgery, while only one patient achieved radiographic PR according to the response evaluation criteria in solid tumors (RECIST) ( 23 ). Lee JM, et al.…”