ORIENT-12 Study: Addition of Sintilimab to Gemcitabine/Platinum in Advanced Squamous NSCLC

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Adding sintilimab to a regimen of gemcitabine and platinum demonstrated clinical benefit over gemcitabine and platinum alone as first-line therapy in patients with locally advanced or metastatic squamous non–small cell lung cancer (NSCLC). These results from the ORIENT-12 trial were published by Zhou et al in the Journal of Thoracic Oncology.

The standard chemotherapy for squamous NSCLC includes platinum plus gemcitabine. Sintilimab—an anti–PD-1 antibody—plus platinum/gemcitabine has shown encouraging efficacy as first-line therapy for squamous NSCLC in the phase III ECOG 1594 study. 


Researchers conducted a randomized double-blind phase III trial to further compare the efficacy and safety of sintilimab with placebo, both in combination with gemcitabine/platinum. Patients with locally advanced or metastatic squamous NSCLC and without EGFR-sensitive mutations or ALK rearrangements were included in the trial. 

Overall, researchers screened 543 patients from 42 centers throughout China. Of those, 357 patients were randomly assigned to receive sintilimab plus gemcitabine/platinum (n = 179) or placebo plus gemcitabine/platinum (n = 178).

The primary endpoint was progression-free survival (defined as the time from random assignment to the first disease progression or death from any cause) as assessed by the independent radiographic review committee.

Improvement in Progression-Free Survival

After a median follow-up period of 12.9 months, patients in the sintilimab plus gemcitabine/platinum group continued to demonstrate a meaningful improvement in progression-free survival over the placebo plus gemcitabine/platinum group (hazard ratio = 0.536, 95% confidence interval = 0.422–0.681, P < .00001). The incidence of treatment-emergent adverse events leading to death was 4.5% and 6.7%, respectively.

“In this study, the risk of disease progression or death was reduced by 37.9% at interim analysis and by 46.4% at updated analysis,” said first author Caicun Zhou, MD, PhD. “The results from ORIENT-12 could provide a new option for combination therapy in this patient population.”

The study authors concluded, “In terms of progression-free survival, sintilimab plus gemcitabine/platinum demonstrates clinical benefit over gemcitabine/platinum alone as first-line therapy in patients with locally advanced or metastatic squamous NSCLC. The toxicity was acceptable, and no new unexpected safety signals were observed.”

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