Generalizability of ORIENT-11 trial results to a US standard of care cohort with advanced non-small-cell lung cancer

Aim: This retrospective study estimated efficacy and safety of sintilimab + pemetrexed + platinum (SPP) versus placebo + pemetrexed + platinum (PPP) in untreated locally advanced/metastatic, nonsquamous non-small-cell lung cancer (NSCLC), after adjusting each ORIENT-11 trial patient's contribution to ORIENT-11 data based on characteristics of a target US population. Materials & methods: The target US population (n = 557) was selected from a real-world deidentified advanced NSCLC database based on key ORIENT-11 eligibility criteria. Inverse probability weights for ORIENT-11 patients (n = 397) relative to US patients were calculated. Efficacy and safety of SPP versus PPP were adjusted by inverse probability weights. Results: After adjustment, progression-free survival remained superior for SPP. Other efficacy and safety outcomes were consistent. Conclusion: These results provide evidence on how the effects observed with SPP in ORIENT-11 could translate to a US population with untreated locally advanced/metastatic nonsquamous NSCLC. Plain language summary Sintilimab is an immunotherapy drug that was successfully developed and tested in China for untreated locally advanced/metastatic nonsquamous non-small-cell lung cancer. To assess if results from the Chinese ORIENT-11 trial are applicable to the US population, this study used US real-world patient data to adjust the ORIENT-11 trial analysis. After adjustment, progression-free survival benefit observed in ORIENT-11 with the addition of sintilimab to standard chemotherapy remained superior, and other efficacy and safety end points were consistent. This finding may help inform clinical decisions about the applicability of ORIENT-11 trial results to US patients with untreated locally advanced/metastatic nonsquamous NSCLC. In addition, this study offers another way real-world evidence can be applied to help complement clinical trial evidence and optimize treatment decisions.