Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

Platinum versus immunotherapy for early resectable non-small cell lung cancer: A protocol for systematic review and meta analysis.

BACKGROUND: Lung cancer is one of the most common malignant tumors. Non-small cell Lung cancer (NSCLC) accounts for about 85% of the total lung cancer. For patients with resectable early NSCLC, conventional postoperative adjuvant therapy can significantly prolong the overall survival of patients and reduce the risk of tumor recurrence. With the emergence and maturity of molecular targeted therapy and immunotherapy, the strategy of postoperative chemotherapy for lung cancer patients has changed greatly. To evaluate the efficacy of postoperative chemotherapy (platinum based chemotherapy and immunotherapy) with or without radiotherapy for NSCLC patients, we will conduct a systematic review and meta-analysis of published or unpublished randomized controlled trials. METHODS: We will search Pubmed (Medline), Embase, Google Scholar, Cancerlit, and the Cochrane Central Register of Controlled Trials for related studies published without language restrictions before June 20, 2021. Two review authors will search and assess relevant studies independently. Randomized controlled trials and quasi-randomized controlled trials studies will be included. we will perform subgroup analysis in different methods of postoperative adjuvant therapy for patients with resectable early NSCLC. Because this study will be based on published or unpublished records and studies, there is no need for ethics approval. INPLASY registration number: INPLASY202080064. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will compare the efficacy of platinum chemotherapy and immunotherapy in patients with resectable early NSCLC. Since the large sample randomized trials that meet the inclusion criteria of this study may be inadequate, we will consider incorporating some high quality small sample related tests, which may lead to heterogeneity and affect the reliability of the results.

Postoperative adjuvant therapy for resectable early non-small cell lung cancer: A protocol for a systematic review and meta-analysis.

BACKGROUND: Lung cancer is one of the most common malignant tumors, and non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer diagnosed. For patients with resectable early stage non-small cell lung cancer, routine postoperative adjuvant therapy can significantly prolong overall patient survival and reduce the risk of cancer recurrence. With the emergence and maturity of molecular targeted therapy and immunotherapy, the postoperative chemotherapy strategy of lung cancer patients has changed a lot. To evaluate the efficacy of postoperative adjuvant therapy (platinum-based chemotherapy, platinum-based chemotherapy plus molecular targeted therapy, platinum-based chemotherapy plus anti-angiogenic agents, or platinum-based chemotherapy plus immunotherapy) with or without radiotherapy for patients with NSCLC, we will conduct a systematic review and meta-analysis of the published or unpublished relevant randomized controlled trials. METHODS: We will search PubMed (Medline), Embase, Google Scholar, Cancerlit, and the Cochrane Central Register of Controlled Trials for related studies published without language restrictions before June 20, 2019. Two review authors will search and assess relevant studies independently. Randomized controlled trials (RCTs) and quasi-RCTs studies will be included. We will perform subgroup analysis in different methods of postoperative adjuvant therapy for patients with resectable early NSCLC. Because this study will be based on published or unpublished records and studies, there is no need for ethics approval. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will comprehensively compare the efficacy of platinum-based chemotherapy with that of molecular targeted therapy and immunotherapy for patients after surgery with resectable early NSCLC. Since large-sample randomized trials meeting the inclusion criteria of this study may be insufficient, we will consider incorporating some high-quality small-sample-related trials, which may lead to high heterogeneity and affect the reliability of the results.

[Impact of intrapleural hyperthermic perfusion on immunologic reaction state of cytokines TH1/TH2 of lung carcinoma patients with malignant pleural effusion].

BACKGROUND & OBJECTIVE: Intrapleural hyperthermic perfusion is the distinctive therapy of malignant pleural effusion (MPE) caused by lung carcinoma. The expression pattern of T helper type 1 (Th1)/Th2 is an important index that reflects antitumor immunologic function. This study was to evaluate the therapeutic effect of intrapleural hyperthermic perfusion on MPE, and to investigate the impact of intrapleural hyperthermic perfusion on the immunologic reaction state of lung carcinoma patients with MPE by observing the expression pattern of cytokines Th1/Th2. METHODS: A total of 24 lung carcinoma patients with MPE underwent intrapleural hyperthermic perfusion with 43 celsius warmed normal saline for 60 min under video-assisted thoracoscopic surgery (VATS). The responses of pleural effusion, adverse events, life quality and survival time were observed. The concentrations of Th1/Th2-related cytokines interferon-gamma (IFN-gamma), interleukin-2 (IL-2)/IL-4, and IL-10 in peripheral blood and pleural effusion were detected by ELISA, and their mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Neither operation-related death nor postoperative complication occurred. The total response rate of pleural effusion control was 100%, including 23 cases of complete remission (CR) and 1 case of partial remission (PR). No recurrence of MPE occurred. The quality of life of all patients had been improved. The median survival time was 18.3 months. The 1-and 2-year survival rates were 91.7% and 16.7%. The concentrations and positive rates of IL-2 and IFN-gamma were significantly lower and those of IL-4 and IL-10 were significantly higher in peripheral blood and pleural effusion before hyperthermia than in those after hyperthermia (P<0.05). CONCLUSIONS: Intrapleural hyperthermic perfusion under VATS is a safe and effective treatment for MPE caused by lung carcinoma. It can convert the predominant state of Th2 cytokines in lung carcinoma patients with MPE to that of Th1 cytokines.