4MO Final overall survival (OS) data of sintilimab plus pemetrexed (SPP) and platinum as first-line (1L) treatment for locally advanced or metastatic nonsquamous NSCLC (AMnsqNSCLC) in the phase III ORIENT-11 study

Immunotherapy combined with chemotherapy versus chemotherapy alone as the first‐line treatment of PD‐L1‐negative and driver‐gene‐negative advanced nonsquamous non‐small‐cell lung cancer: An updated systematic review and meta‐analysis

“…For PFS, the improvement was statistically significant in immunotherapy in combination with chemotherapy versus chemotherapy in the Keynote‐021G, KEYNOTE‐189, IMPOWER‐130, and IMPOWER‐132 trials among the six trials with available data 17,19,20 . In the four trials with available OS data that were enrolled in this meta‐analysis, only the Keynote‐189 trial showed that pembrolizumab combined with platinum + pemetrexed showed a significant improvement in OS compared with platinum + pemetrexed in the treatment of patients with PD‐L1‐negative and driver‐gene‐negative advanced nonsquamous NSCLC, but the differences between the two treatment modalities were not statistically significant in other trials (KEYNOTE‐021G, IMpower130, and ORIENT 11 trials) 17–19,23 . The updated data from the KEYNOTE‐189 study (23.1‐month follow‐up time) demonstrated that the median OS (mOS) of patients with PD‐L1‐negative and driver‐gene‐negative advanced nonsquamous NSCLC was 17.2 months in the pembrolizumab + platinum + pemetrexed group versus 10.2 months in the platinum + pemetrexed group (HR 0.52, 95% CI 0.36–0.74); the median PFS (mPFS) was 6.2 months and 5.1 months, respectively (HR 0.64, 95% CI 0.47–0.89) 18 .…”

“…The IMPOWER130 and IMPOWER 132 trials compared the clinical benefit achieved in patients in the atezolizumab + chemotherapy group versus the chemotherapy group 19,20 . The CameL, RATIONALE 304, and ORIENT 11 trials compared the efficacy of three PD‐1 inhibitors produced in China (carrelizumab, tislelizumab, and sintilizumab) combined with chemotherapy versus chemotherapy in the treatment of patients with PD‐L1‐negative and driver‐gene‐negative advanced nonsquamous NSCLC 21–23 . The baseline characteristics and the outcome measures of the included studies are shown in Table 1.…”

The Applicability of the Results in the Asian Population of ORIENT-11 to a Western Population According to the ICH-E5 Framework

“…Furthermore, in a mixed lymphocyte reaction assay, sintilimab increased interleukin-2 and interferong in a dose-dependent manner, similar to nivolumab; however, sintilimab did not induce cytokine release (8). Gene expression analyses evaluating the association between clinical outcome with sintilimab and a specific immune cell signature revealed that a longer PFS and/or OS was attained in patients who had a higher MHC-II-associated gene expression (10), which has also been previously observed with pembrolizumab and nivolumab (21,22). This potentially implicates antigen presentation pathways, such as MHC-II pathway, in the mechanism of action and a crucial component to attain clinical benefit from sintilimab combination therapy (10).…”

“…The updated OS analysis (data cutoff: January 15, 2021) of ORIENT-11 with a median follow-up of 22.9 months continued to demonstrate an improved OS with the addition of sintilimab to chemotherapy. Median OS was still not reached in the sintilimab arm compared with 16.8 months in the control arm (Table 2) (10). Despite a crossover rate in ORIENT-11 of 45.8% from the control arm to the sintilimab arm following disease progression, in line with KEYNOTE-189 (41.3%) (4), OS was still more favorable in the sintilimab combination arm [HR = 0.60 (95% CI: 0.45-0.79); p = 0.0003; data cutoff: January 2021].…”

“…Sintilimab is a recombinant fully human immunoglobulin G (IgG4) anti-PD-1 monoclonal antibody which has demonstrated both preclinical activity as monotherapy (7,8) and clinical benefit when used in combination with pemetrexed and platinum chemotherapy for NSCLC (9). The ORIENT-11 trial demonstrated improved OS, PFS, and objective response rate (ORR) with the addition of sintilimab to pemetrexed plus platinum (10). The ORIENT-11 results support sintilimab plus platinum and pemetrexed as a novel first-line treatment option for nonsquamous NSCLC.…”