Sintilimab plus chemotherapy for first-line treatment of advanced or metastatic nonsquamous non-small-cell lung cancer: network meta-analysis.

Aim: This systematic literature review and network meta-analysis evaluated the efficacy and safety of sintilimab + pemetrexed + platinum versus US FDA-approved/National Comprehensive Cancer Network-recommended immune checkpoint inhibitor (ICI) combination therapies for untreated advanced/metastatic non-squamous non-small-cell lung cancer without EGFR/ALK aberrations. Methods: Bayesian network meta-analysis was the base-case analysis and included assessment of fixed and random effects, and independent and simultaneous models, adjusting for baseline risk (placebo response). Chemotherapy was the common comparator. Results: Sintilimab + pemetrexed + platinum was associated with significantly longer progression-free survival than atezolizumab + platinum + nab-paclitaxel (hazard ratio [HR]: 0.57; 95% credible interval [CrI]: 0.40-0.82) and nivolumab + ipilimumab + pemetrexed + platinum (HR: 0.66; 95% CrI: 0.48-0.92). Sintilimab + pemetrexed + platinum and pembrolizumab + pemetrexed + platinum showed comparable progression-free survival (HR: 0.96; 95% CrI: 0.71-1.30). There was no significant difference in overall survival (HR range: 0.61-0.81) or overall response rates (odds ratio [OR] range: 0.29-0.75) between sintilimab + pemetrexed + platinum and the other ICI combinations. The incidence of high-grade adverse events was higher with sintilimab + pemetrexed + platinum than with nivolumab + ipilimumab (OR: 0.46; 95% CrI: 0.33-0.64) or without chemotherapy (OR: 0.25; 95% CrI: 0.19-0.34), with no significant difference between sintilimab + pemetrexed + platinum and the other ICI combinations. Conclusion: Sintilimab + pemetrexed + platinum showed comparable efficacy and safety versus US standard-of-care first-line ICI combinations for advanced/metastatic non-squamous non-small-cell lung cancer.

Sintilimab is an immunotherapy drug that was successfully developed and tested in China to treat a kind of lung cancer that has spread, called advanced non-squamous non-small-cell lung cancer (NSCLC). The ORIENT-11 clinical study showed that adding sintilimab to two types of chemotherapy (pemetrexed and platinum) as the first treatment for people in China with advanced non-squamous NSCLC was safe and effective in reducing the risk of cancer spreading, growing or getting worse, compared with chemotherapy alone. Our study combined and analyzed the results from 11 clinical studies to look at how well sintilimab with chemotherapy may work compared with immunotherapy drugs approved in the USA. The results showed that sintilimab with chemotherapy is as effective and safe as immunotherapy drugs approved in the USA to treat people with advanced non-squamous NSCLC. These results may help doctors and payers when deciding how to treat people with this disease.

Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases.

BACKGROUND: An advance in the treatment of schizophrenia is the development of long-acting intramuscular formulations of antipsychotics, such as olanzapine long-acting injection (LAI). During clinical trials, a post-injection syndrome characterized by signs of delirium and/or excessive sedation was identified in a small percentage of patients following injection with olanzapine LAI. METHODS: Safety data from all completed and ongoing trials of olanzapine LAI were reviewed for possible cases of this post-injection syndrome. Descriptive analyses were conducted to characterize incidence, clinical presentation, and outcome. Regression analyses were conducted to assess possible risk factors. RESULTS: Based on approximately 45,000 olanzapine LAI injections given to 2054 patients in clinical trials through 14 October 2008, post-injection delirium/sedation syndrome occurred in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients). Symptomatology was consistent with olanzapine overdose (e.g., sedation, confusion, slurred speech, altered gait, or unconsciousness). However, no clinically significant decreases in vital signs were observed. Symptom onset ranged from immediate to 3 to 5 hours post injection, with a median onset time of 25 minutes post injection. All patients recovered within 1.5 to 72 hours, and the majority continued to receive further olanzapine LAI injections following the event. No clear risk factors were identified. CONCLUSIONS: Post-injection delirium/sedation syndrome can be readily identified based on symptom presentation, progression, and temporal relationship to the injection, and is consistent with olanzapine overdose following probable accidental intravascular injection of a portion of the olanzapine LAI dose. Although there is no specific antidote for olanzapine overdose, patients can be treated symptomatically as needed. Special precautions include use of proper injection technique and a post-injection observation period. TRIAL REGISTRATION: ClinicalTrials.gov ID; URL: http://http//www.clinicaltrials.gov/: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.