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.

Anti-angiogenic agents combined with immunotherapy for advanced non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: Anti-angiogenic agents could enhance tumor immunity response, and anti-angiogenesis plus immunotherapy has become a novel treatment option for advanced non-small cell lung cancer (NSCLC). The efficacy of this combination therapy remains controversial and obscure. AIM: We conducted a meta-analysis to evaluate the clinical efficacy and safety of this therapeutic strategy in patients with advanced NSCLC and provide more guidance for treating NSCLC clinically. METHODS: A systematic literature search was performed in PubMed, Embase, Web of Science, CNKI, and Wanfang databases to identify relevant studies published up to December 2021. The primary endpoint was the objective response rate (ORR). Second endpoints were progression-free survival (PFS), overall survival (OS), and grade ≥3 AEs adverse events (AEs). The sensitivity analysis was conducted to confirm the stability of the results. STATA 15.0 was utilized for all pooled analyses. RESULTS: Eleven studies were eventually included in the meta-analysis, involving 533 patients with advanced NSCLC. The pooled ORR rate was 27% (95% CI 18% to 35%; I2 =84.2%; p<0.001), while the pooled median PFS and OS was 5.84 months (95% CI 4.66 to 7.03 months; I2=78.4%; p<0.001) and 14.20 months (95% CI 11.08 to 17.32 months; I2=82.2%; p=0.001), respectively. Most common grade ≥3 AEs included hypertension, hand-foot syndrome, diarrhea, adrenal insufficiency, hyponatremia, proteinuria, rash, thrombocytopenia, and fatigue. CONCLUSION: Anti-angiogenesis combined with immunotherapy demonstrated satisfactory antitumor activity and an acceptable toxicity profile in patients with advanced NSCLC. The pooled results of our meta-analysis provided further evidence supporting the favorable efficacy and safety of this therapeutic strategy.

Clinical analysis of anlotinib as first-line treatment for elderly patients with advanced lung adenocarcinoma without driver gene mutations.

This retrospective study was conducted to explore the effects of anlotinib as first-line treatment for patients with advanced lung adenocarcinoma. We retrospectively reviewed medical records of 60 patients with advanced lung adenocarcinoma, admitted to the Fuzhou Pulmonary Hospital between August 2018 and December 2019. We calculated and recorded the objective remission rate (ORR), disease control rate (DCR), adverse reactions, quality of life assessment, progression-free survival (PFS) and overall survival (OS) for each group. We applied χ2, Mann-Whitney U test, Kaplan-Meier and log-rank statistical methods as appropriate to analyze the data. We found no statistically significant differences in either ORR (17.5 vs. 15%) or DCR (67.5 vs. 65.5%) between the anlotinib and pemetrexed groups (P > 0.05). The adverse reactions graded ≥3 in the anlotinib group were fatigue and diarrhea and they accounted for 5% of all the adverse reactions in the group. The patients in the anlotinib group presented better physical, role, cognitive, emotional, and social functions than those in the pemetrexed group (P < 0.05). The symptoms of fatigue, nausea and vomiting, loss of appetite and constipation in the anlotinib group were significantly less frequent than those in the pemetrexed group (P < 0.05). We found similar median PFSs (3.0 vs. 2.8 months) and median OSs (7.0 vs. 7.0 months) in both treatment groups (P > 0.05). The choice of anlotinib as first-line chemotherapy for treating elderly patients with advanced lung adenocarcinoma was effective, safe; the treatment was better than other drugs at improving the patients' quality of life.