Camrelizumab, chemotherapy and apatinib in the neoadjuvant treatment of resectable oesophageal squamous cell carcinoma: a single-arm phase 2 trial

Background In resectable oesophageal squamous cell carcinoma (ESCC), the eff i cacy of camrelizumab combined with chemotherapy and apatinib followed by minimally invasive oesophagectomy is not clear. We aimed to fi ll this knowledge gap. Methods This investigator-initiated, single-arm, prospective, phase 2 trial was performed at the Second Aff i liated Hospital of Zhejiang University, China. Patients (aged 18 - 75 years) who were histologically or cytologically diagnosed with ESCC were deemed suitable to participate in this trial. Patients received 2 - 3 cycles of neoadjuvant therapy with camrelizumab, nedaplatin, albumin paclitaxel, and apatinib; each cycle was repeated every 14 days. Surgery occurred 4 - 6 weeks after the last neoadjuvant treatment cycle. The primary outcome was the pathological complete response (PCR) rate of the tumour and lymph nodes. The changes in the peripheral blood immunopro fi le among patients without PCR (ie, non-PCR [NPCR]) and with PCR were assessed by mass cytometry. This study was registered with ClinicalTrials.gov, NCT04666090. Findings 42 patients were enrolled between November 23, 2020 and December 31, 2022. The disease control rate was 100.0% (95% CI, 91.6 - 100%), and the objective response rate was 83.3% (95% CI, 68.6 - 93.0%). Six (14.3%) patients experienced grade 3 adverse events. The most common were white blood cell count decrease (31.0%), alopecia (81.0%), asthenia (38.1%), and reactive cutaneous capillary endothelial proliferation (35.7%). 41 patients received minimally invasive oesophagectomy; all 41patients achieved R0 resection, and 18 (43.9%, 95% CI, 28.5 - 60.3%) patients achieved PCR. The median follow-up was 23 months and the 2-year survival rate was 85.9%. T-cell subsets in both the PCR and NPCR groups exhibited consistency in response to neoadjuvant therapy. In contrast, some of natural killer (NK) cells (NK-C03, NK-C11), B cells (B -C06) and monocytes (M -C05), exhibited signi fi cant differences between the PCR and NPCR groups before neoadjuvant therapy. M -C06 had a signi fi cant difference in the PCR group and NPCR group after neoadjuvant therapy. NK-C12 and B -C15 showed signi fi cant differences both before and after neoadjuvant therapy. Interpretation The application of camrelizumab, chemotherapy and apatinib in the neoadjuvant setting for locally advanced ESCC has shown promising antitumour activity and an acceptable safety pro fi le in this single-arm study. In the neoadjuvant setting, NK cell, B cell, and monocyte subsets exhibited greater predictive power for immunotherapy responsiveness than T-cell subsets. Longer follow-up to assess survival outcomes and a phase 3 randomised trial are needed to further evaluate the proposed treatment.