Sintilimab provided superior clinical benefit compared to docetaxel in patients with previously treated, advanced and/or metastatic squamous non–small cell lung cancer (NSCLC), according to phase III study findings presented by Shi et al at the European Society for Medical Oncology (ESMO) Immuno-Oncology Virtual Congress 2020 (Abstract 30MO).
ORIENT-3
The phase III ORIENT-3 study evaluated the efficacy and safety of sintilimab, an anti–PD-1 monoclonal antibody, compared with docetaxel as second-line treatment in squamous NSCLC.
The study enrolled patients with stage IIIB/IIIC or IV squamous NSCLC who were ineligible for radical chemoradiotherapy and had failed first-line platinum-based chemotherapy. Following 1:1 random assignment, 145 patients received sintilimab at 200 mg and 145 received docetaxel at 75 mg/m2; both agents were delivered intravenously every 3 weeks until disease progression or intolerable toxicity.
In addition, patients were stratified according to Eastern Cooperative Oncology Group (ECOG) performance score of 0 vs 1. The patients’ baseline characteristics were well-balanced between treatment groups, with the majority (75.9% vs 77.0% in the sintilimab and docetaxel arms, respectively) having an ECOG performance score of 1.
Overall survival was the primary study endpoint.
Results
As of July 31, 2020, a median of 8.0 cycles of sintilimab (range = 1–45) and 2.0 cycles of docetaxel (range = 1–15) had been administered. The efficacy analysis comprised 280 patients in the full analysis set; 10 patients in the docetaxel arm were excluded from the full analysis set due to initiation of immunotherapy before receiving docetaxel treatment or before radiographic disease progression on study treatment.
With a median of 23.56 months, the patients treated with sintilimab demonstrated improved overall survival compared to those treated with docetaxel; median overall survival was 11.79 months (95% confidence interval [CI] = 10.28–15.57) vs 8.25 months (95% CI = 6.47–9.82) (hazard ratio [HR] = 0.74, 95% CI = 0.56–0.96, P = .02489).
The median progression-free survival was significantly prolonged—4.30 months (95% CI = 4.04–5.78) in the sintilimab group compared to 2.79 months (95% CI = 1.91–3.19) in the docetaxel group (HR = 0.52, 95% CI = 0.39–0.68, P < .00001).
The response was more than fivefold higher with sintilimab, with an objective response rate of 27.6 % (95% CI = 20.5–35.6) compared to 5.2% (95% CI = 2.1–10.4) with docetaxel.
The safety analysis was done in the safety set of 274 patients (n = 144 in sintiliamb arm, n = 130 in docetaxel arm); 84.7% of patients receiving sintilimab and 83.1% of patients receiving docetaxel reported treatment-related adverse events. Treatment-related adverse events of at least grade 3 occurred at half the frequency with sintilimab vs docetaxel (18.1% vs 36.2%, respectively).
Based on these findings, the authors were able to conclude that sintilimab as second-line treatment for advanced/metastatic squamous NSCLC provided superior overall and progression-free survival compared to docetaxel.
Disclosure: Funding for this study was reported from Innovent Biologics, Inc, and Eli Lilly and Company. For full disclosures of the study authors, visit annalsofoncology.org.
