Sintilimab provided superior clinical benefit compared to docetaxel in patients with previously treated advanced and/or metastatic squamous non-small cell lung cancer (sqNSCLC), according to phase III study findings presented at the ESMO Immuno-Oncology Virtual Congress 2020, held from 9 to 12 December 2020.

Yuankai Shi of the Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing, China presented results from the phase III ORIENT-3 study (NCT03150875), which evaluated the efficacy and safety of sintilimab compared with docetaxel as second-line treatment in sqNSCLC. Sintilimab is a monoclonal antibody targeting the programmed-death-receptor-1 (PD-1).

The study enrolled patients with stage IIIB/IIIC or IV sqNSCLC who were ineligible for radical chemo-radiotherapy and had failed first-line platinum-based chemotherapy. Following 1:1 randomisation, 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 ECOG performance score of 0 versus 1. The patients’ baseline characteristics were well balanced between treatment groups, with the majority (75.9% versus 77.0% in the sintilimab versus docetaxel arms, respectively) having an ECOG performance score of 1.

Overall survival (OS) served as the primary study endpoint.

Second-line sintilimab showed greater clinical benefit than docetaxel

As of 31 July 2020, a median of 8.0 cycles of sintilimab (range, 1 to 45) and 2.0 cycles of docetaxel (range, 1 to 15) had been administered. The efficacy analysis comprised 280 patients in the full analysis set (FAS), 10 patients in the docetaxel arm were excluded from FAS 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 OS compared to docetaxel; median OS was 11.79 months (95% confidence interval [CI] 10.28-15.57) versus 8.25 months (95% CI 6.47-9.82) respectively (hazard ratio [HR] 0.74; 95% CI 0.56-0.96; p = 0.02489).

The median progression-free survival (PFS) was significantly prolonged, with 4.30 months (95% CI 4.04-5.78) in sintilimab group compared to 2.79 months (95% CI 1.91-3.19) in docetaxel group (HR 0.52; 95% CI 0.39-0.68; p < 0.00001).


Overall survival and progression-free survival in the ORIENT-3 study.

© Yuankai Shi.

The response was more than 5-fold higher with sintilimab, where the objective response rate was 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) and revealed a similar prevalence of adverse events (AEs) in the treatment arms; 84.7% of patients on sintilimab and 83.1% of patients receiving docetaxel reported treatment-related AEs (TRAEs). TRAEs ≥ grade 3 occurred at half the frequency with sintilimab versus docetaxel (18.1% versus 36.2%, respectively).


Based upon these findings, the authors were able to conclude that sintilimab as second-line treatment for advanced/metastatic sqNSCLC provided superior OS and PFS as compared with docetaxel.

Funding for this study was reported from Innovent Biologics, Inc. and Eli Lilly and Company.


30MO – Shi Y, Wu L, Yu X, et al. ORIENT-3: A randomized, open-label, phase III study of sintilimab versus docetaxel in previously treated advanced/metastatic squamous non-small cell lung cancer (sqNSCLC). ESMO Immuno-Oncology Virtual Congress 2020 (9-12 December).