Clinical benefit of neoadjuvant immunotherapy in resectable esophageal squamous cell carcinoma (ESCC). remains unclear. This study evaluated the efficacy and safety of the programmed death 1 (PD-1) inhibitor tislelizumab combined with chemotherapy as neoadjuvant therapy in patients with resectable ESCC. Treatment-naïve patients were enrolled and eligible patients received 3 cycles of neoadjuvant therapy with tislelizumab, carboplatin, and nab-paclitaxel. The primary endpoint was surgery patients major pathological response (MPR). Subgroup analysis was stratified by tumor downstaging, circumferential resection margin (CRM), PD-ligand 1 (PD-L1) expression, and tumor mutation burden (TMB). Safety was assessed by adverse events (AEs) and postoperative complications. Between September 2020 and March 2021, 45 patients were enrolled. Thirty-six (80.0%) of 45 patients underwent surgery, and 29 (80.5%) underwent successful R0 resection. MPR and pathological complete response (pCR) for surgery patients were 72.0% and 50.0%, respectively. Intention to treatment (ITT) patients MPR and PCR were 57.5% and 40%. Downgrading occurred in 75% of 36 patients. MPR and pCR were identified to be associated with tumor downstaging and CRM but not PD-L1 expression or TMB. TPS levels in MPR and pCR group were significantly higher than that in Non-MPR and Non-pCR group, respectively. Treatment-related AEs of grade 3-4 and immune-related AEs occurred in 42.2% and 22.2% of 45 patients, respectively, and postoperative complications occurred in 77.8% of 36 patients. No treatment-related surgical delay or death occurred. No associations between gene mutation and pathological efficacy were observed. Tislelizumab plus chemotherapy as neoadjuvant therapy demonstrates promising antitumor activity for resectable ESCC with high rates of MPR, pCR, and R0 resection, as well as acceptable tolerability.

Importance: The benefit of neoadjuvant camrelizumab plus chemotherapy for resectable stage IIIA or IIIB non–small cell lung cancer (NSCLC) remains unknown.Objective: To assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy vs chemotherapy alone for patients with resectable stage IIIA or IIIB NSCLC.Design, Setting, and Participants: In this randomized phase 2 clinical trial conducted at 2 hospitals in China, patients aged 18 to 70 years with resectable stage IIIA or IIIB (T3N2) NSCLC were enrolled between April 7, 2020, and January 12, 2022.Interventions: Patients were randomly assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m², and platinum [cisplatin, 75 mg/m²; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m²]) or chemotherapy alone, followed by surgery after 4 to 6 weeks.Main Outcomes and Measures: The primary end point was the pathologic complete response (pCR) rate. Secondary end points included the major pathologic response (MPR) rate, objective response rate (ORR), event-free survival (EFS), and safety. Disease-free survival (DFS, defined as the time from surgery to disease recurrence or death from any cause) was analyzed post hoc. Efficacy was assessed on a modified intention-to-treat basis.Results: Ninety-four Chinese patients were randomized, and 88 (93.6%; median age, 61 years [IQR, 54-65 years]; 74 men [84.1%]) received allocated neoadjuvant treatment (43 received camrelizumab plus chemotherapy, and 45 received chemotherapy alone). Among these 88 patients, the pCR rate was 32.6% (14 of 43; 95% CI, 19.1%-48.5%) with camrelizumab plus chemotherapy vs 8.9% (4 of 45; 95% CI, 2.5%-21.2%) with chemotherapy alone (odds ratio, 4.95; 95% CI, 1.35-22.37; P = .008). The MPR rates were 65.1% (95% CI, 49.1%-79.0%) with camrelizumab plus chemotherapy and 15.6% (95% CI, 6.5%-29.5%) with chemotherapy alone. The radiographic ORRs were 72.1% (95% CI, 56.3%-84.7%) with camrelizumab plus chemotherapy and 53.3% (95% CI, 37.9%-68.3%) with chemotherapy alone. With a median follow-up of 14.1 months (IQR, 9.2-20.9 months), the median EFS and DFS were not reached in either group. The most common neoadjuvant treatment-related adverse events of grade 3 or higher were decreased white blood cell count (6 of 43 [14.0%] in the camrelizumab plus chemotherapy group vs 2 of 45 [4.4%] in the chemotherapy group) and decreased neutrophil count (3 of 43 [7.0%] in the camrelizumab plus chemotherapy group vs 5 of 45 [11.1%] in the chemotherapy group). No treatment-related deaths were reported.Conclusions and Relevance: This randomized clinical trial found that among patients with resectable stage IIIA or IIIB (T3N2) NSCLC, camrelizumab plus chemotherapy, compared with chemotherapy alone, significantly improved the pCR rate with manageable toxic effects.Trial Registration: ClinicalTrials.gov Identifier: NCT04338620

Histone deacetylase (HDAC) inhibitors, developed as promising anti-tumor drugs, exhibit their anti-inflammatory properties due to their effects on reduction of inflammatory cytokines.

Neoadjuvant immunotherapy for patients with locally advanced esophageal cancer (EC) has developed rapidly in recent years. The efficacy and safety outcomes may change the recommended neoadjuvant therapeutic regimens for patients with EC. Systematic screening for articles focusing on the efficacy and safety of neoadjuvant immunotherapy in locally advanced and surgically resectable EC was performed using PubMed, Embase, Web of Science and international tumor congresses. Meta-analysis of non-comparative binary outcomes was carried out to combine the main results. The pooled results were compared with the traditional neoadjuvant chemotherapy (nCT) and chemoradiotherapy (nCRT) using direct comparative analysis. The results were expressed as the risk ratio (RR). A total of 20 articles with 621 patients were included in the present study. The pooled pathological complete response and major pathological response rates were 33.8% (95% CI: 29.6%-37.9%) and 53.5% (95% CI: 47.9%-59%), respectively, in the neoadjuvant immunotherapy combined with chemotherapy (nICT) group and 39.8% (95% CI: 27%-53.9%) and 88.8% (95% CI: 64.8%-97.2%) in the neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT) group, respectively. In addition, the pooled grade 3-4 treatment-related adverse events (TRAEs) rate was 19.4% (95% CI: 11.5%-31.5%) in the nICT group. The results of direct comparison showed that compared with nCRT and nICRT, nICT could improve safety while achieving comparable efficacy. The results of subgroup analysis, sensitivity analysis and publication bias evaluation indicated that the above findings were stable and reliable. The current meta-analysis revealed that neoadjuvant immunotherapy in patients with locally advanced EC was safe and effective and nICT could be used as the recommended neoadjuvant therapeutic option for patients with EC. However, additional studies are urgently needed to reveal the long-term outcomes of neoadjuvant immunotherapy.