Adding Sintilimab to Platinum Plus Gemcitabine Demonstrated Clinical Benefit in First-Line Squamous NSCLC

Sintilimab with gemcitabine plus platinum produced superior clinical benefit for patients with locally advanced or metastatic squamous cell non–small cell lung cancer when compared with gemcitabine plus platinum alone.

The addition of sintilimab (Tyvyt) to gemcitabine and platinum (GP) demonstrated a clinical benefit in progression-free survival (PFS) over GP alone in patients with locally advanced or metastatic squamous cell nonsmall cell lung cancer (sqNSCLC) in the first-line setting, according to data from the phase 3 ORIENT-12 trial (NCT03629925).1

At the October 15, 2019 interim analysis data cutoff point, the median (PFS) as assessed by independent radiographic review committee (IRRC) was 5.1 months for patients in the sintilimab/GP group (95% CI, 4.9-5.7) compared with 4.9 months (95% CI, 4.8-5.0) for patients in the placebo-GP group (HR = 0.621; 95% CI, 0.473–0.815; P = .00056). At 6 months, the PFS rate was 41.4% (95% CI, 32.8%-49.8%) in the sintilimab/GP group and 24.7% (95% CI, 17.8-32.2) in the placebo/GP group. The median follow-up was 8.0 months (range, 0.5-12.6).

“In this phase 3 study, sintilimab in combination with GP revealed a significant PFS benefit compared with placebo plus GP as first-line therapy in patients with advanced or metastatic sqNSCLC,” the investigators wrote. “This result confirmed the findings from a previous phase 1b study, which revealed a clinical benefit with the addition of sintilimab to standard GP chemotherapy compared with historical results for GP treatment alone.”

A total of 357 patients were enrolled between September 25, 2018, and July 26, 2019, and randomly assigned to either the sintilimab/GP group (n = 179) or the placebo/GP group (n = 178). The research was conducted across 42 centers throughout China and was led by Caicun Zhou, MD, PhD, of the Shanghai Pulmonary Hospital in Shanghai, China.2

Patients were randomized to receive either 200 mg of sintilimab or matching placebo intravenously (IV) on day 1 every 3 weeks (Q3W) in combination with gemcitabine (1.0 g/m2 IV on day 1 and day 8 Q3W) and either cisplatin (75 mg/m2 IV on day 1 Q3W) or carboplatin (area under the concentration–time curve 5 mg/mL/min IV on day 1 Q3W) for 4 or 6 cycles.

Additional data from the study indicated that the median overall survival (OS) was not reached at the interim analysis. Compared with the placebo/GP group, the sintilimab/GP arm demonstrated a benefit trend (HR = 0.567; 95% CI, 0.353-0.909; P = .01701). At 6 months, OS rates were 91.8% (95% CI, 86.2%-95.2%) and 80.6% (95% CI, 73.6%-85.9%) in the sintilimab/GP and placebo/GP groups, respectively.

At the March 25, 2020, updated analysis cutoff point, median PFS was 5.5 months (95% CI, 4.9-6.8) for the sintilimab/GP group and 4.9 months (95% CI, 4.8-5.0) for the placebo/GP group (HR = 0.536; 95% CI, 0.422-0.681; P < .00001). The 12-month PFS rate was 22.3% (95% CI, 16.0%-29.4%) and 3.1% (95% CI, 1.2-6.7) in the sintilimab/GP and placebo/GP groups, respectively.

The confirmed IRRC-assessed overall response rate (ORR) for patients in the sintilimab/GP group was 44.7% (95% CI, 37.3%-52.3%) and 35.4% (95% CI, 28.4%-42.9%) for patients in the placebo/GP group. Moreover, the median duration of response was 6.1 months (95% CI, 4.7-9.6) in the sintilimab/GP group and 5.1 months (95% CI, 3.7-5.5) in the placebo/GP group.

Any grade treatment-emergent adverse effects (TEAEs) were observed in all patients included in the trial, with grade 3 or higher TEAEs occurring in 155 patients (86.6%) and 148 patients (83.1%) in the sintilimab/GP and placebo/GP groups, respectively.

TEAEs that led to discontinuations were observed in 14.5% (n = 26) and 16.3% (n = 29) of those in the sintilimab/GP and placebo/GP groups, respectively. Additionally, TEAEs leading to death were observed in 8 (4.5%) and 12 patients (6.7%) in both groups, respectively.

Common TEAEs across the sintilimab/GP and placebo/GP cohorts included anemia (93.3% vs 90.4%), decreased white blood cell count (88.8% vs 86.0%), decreased neutrophil count (83.2% vs 82.0%), and decreased platelet count (72.6% vs 70.2%). Grade 3 or worse TEAEs included decreased neutrophil count (48.6% vs 47.8%), decreased platelet count (45.3% vs 42.7%), decreased white blood cell count (36.3% vs 36.5%), and anemia (33.5% vs 32.0%)

“The ORIENT-12 study revealed that the addition of sintilimab to standard chemotherapy with gemcitabine and platinum could significantly prolong the PFS in patients with previously untreated advanced or metastatic sqNSCLC, with manageable safety profiles. The results from ORIENT-12 could provide a new option for combination therapy in this patient population,” the investigators concluded.


  1. Zhou C, Wu L, Fan Y, et al. Sintilimab plus platinum and gemcitabine as first-line treatment for advanced or metastatic squamous NSCLC: results from a randomized, double-blind, phase 3 trial (ORIENT-12). J Thorac Oncol. Published online ahead of print, May 25, 2021;S1556-0864(21)02128-6. doi:10.1016/j.jtho.2021.04.011
  2. ORIENT-12 study demonstrates adding sintilimab to gemcitabine/platinum has clinical benefit. News release. International Association for the Study of Lung Cancer. Published May 25, 2021. Accessed July 20, 2021.