Randomized Phase 3 Study of Sintilimab versus Docetaxel in Advanced Squamous NSCLC (ORIENT-3)

Compared with docetaxel, sintilimab significantly prolonged median overall survival by more than 3 months in patients with advanced squamous non–small-cell lung cancer (NSCLC).

Patients with advanced squamous non–small-cell lung cancer (NSCLC) have few treatment options after failure of a platinum-based doublet chemotherapy regimen. ORIENT-3, a randomized phase 3 study, was conducted to compare the efficacy and safety of sintilimab, an anti–PD-1 antibody, with docetaxel in the second-line treatment of patients with squamous NSCLC.1

Patients with squamous NSCLC (stage IIIB, stage IIIC, or stage IV and ineligible for radical chemo-radiotherapy) who experienced disease progression during or after first-line platinum-based chemotherapy were enrolled in ORIENT-3. They were randomized 1:1 to receive intravenous sintilimab 200 mg or docetaxel 75 mg/m2 every 3 weeks until disease progression or intolerable toxicity. Patient stratification was based on Eastern Cooperative Oncology Group (ECOG) performance status score (0 vs 1). The primary end point of ORIENT-3 was overall survival (OS).1

As of July 31, 2020, 290 patients were enrolled in the study, with 145 patients in each treatment group. The efficacy analysis was based on the final analysis set of 280 patients. The safety analysis was based on the safety set of 274 patients.1

Baseline characteristics were well balanced between the 2 treatment groups. Most patients in the efficacy analysis had an ECOG score of 1: 76% in the sintilimab arm, 77% in the docetaxel arm. Patients received a median of 8 cycles (range, 1-45) of sintilimab, and a median of 2 cycles of docetaxel (range, 1-15).1

After a median follow-up of 23.6 months, sintilimab significantly improved OS versus docetaxel: median 11.8 months (95% confidence interval [CI], 10.3-15.6) versus 8.3 months (95% CI, 6.5-9.8) (hazard ratio [HR], 0.74; 95% CI, 0.56-0.96; P = .025). The median PFS was also significantly superior in the sintilimab arm compared with the docetaxel arm: 4.3 months (95% CI, 4.0-5.8) versus 2.8 months (95% CI, 1.9-3.2) (HR, 0.52; 95% CI, 0.39-0.68; P <.00001). The confirmed ORR was 25.5% (95% CI, 18.6%-33.4%) in the sintilimab arm and 2.2% (95% CI, 0.5%-6.4%) in the docetaxel arm.1

Treatment-related adverse events (TRAEs) were reported in 85% of patients in the sintilimab arm and in 83% of patients in docetaxel arm. The most common TRAEs were hypothyroidism (18%) and alopecia (35%), for sintilimab and docetaxel, respectively. Severe TRAEs (grade ≥3) were less frequent in the sintilimab arm (18%) than in the docetaxel arm (36%). Five patient deaths were related to sintilimab and 1 death was reported as related to docetaxel.1

Researchers concluded that sintilimab used as second-line treatment for advanced and metastatic squamous NSCLC offers superior OS and PFS benefits compared with docetaxel.1

1. Shi Y, Wu L, Yu X, et al. ORIENT-3: a randomized, open-label, phase 3 study of sintilimab versus docetaxel in previously treated advanced/metastatic squamous non-small-cell lung cancer (sqNSCLC). Presented at: American Association of Cancer Research Annual Meeting 2021; April 10-15, 2021. Abstract CT041.