Sintilimab plus chemotherapy improves OS in treatment-naïve, stage III–IV non-squamous NSCLC

The final results of the phase 3 ORIENT-11 trial showed an improved overall survival (OS) in patients with treatment-naïve, stage III–IV non-squamous non-small cell lung cancer (NSCLC) treated with sintilimab plus chemotherapy versus placebo plus chemotherapy.

Antibodies directed at PD-1/PD-L1 are effective therapies for previously untreated patients with metastatic non-squamous NSCLC who do not harbour driver gene mutations. Sintilimab is a selective anti-PD-1 antibody. Preclinical data indicated that sintilimab has a different binding site and therefore potentially greater affinity against PD-1 compared with pembrolizumab or nivolumab [1]. In the phase 3 ORIENT-11 trial (NCT03607539), first-line treatment with sintilimab plus pemetrexed-platinum chemotherapy significantly improved progression-free survival (PFS) compared with placebo plus chemotherapy in patients with stage III–IV non-squamous NSCLC [2]. The final OS results were presented by Dr Yunpeng Yang (Sun Yat-sen University Cancer Center, China) [3].

The ORIENT-11 trial randomised 397 patients with treatment-naïve, stage III–IV non-squamous NSCLC (EGFR/ALK mutation-negative) to sintilimab plus chemotherapy (n=266) or placebo plus chemotherapy (n=131). Participants were stratified by PD-L1 expression, platinum-chemotherapy, and sex. Treatment continued until progressive disease, unacceptable toxicity, or a maximum of 24 months. Participants in the placebo arm were allowed to cross over to receive sintilimab monotherapy upon disease progression.

The median study follow-up for OS was 30.8 months. Of the participants in the placebo arm, 47% crossed over to sintilimab monotherapy. The median OS in the sintilimab arm versus the placebo arm was 24.2 versus 16.8 months (HR 0.65). Estimated 2-year OS rates were 50% and 32%, respectively. OS treatment effect was more pronounced after adjusting for the crossover effect (HR 0.52). The OS benefit of sintilimab in pre-specified subgroups was largely consistent with that of the intention-to-treat population.

In summary, the final analysis of ORIENT-11 continued to demonstrate an improved OS of sintilimab plus chemotherapy compared with placebo plus chemotherapy as first-line therapy in stage III–IV non-squamous NSCLC without EGFR or ALK mutations.

1. Wang J, et al. MAbs. 2019;11:1443–1451.


2. Yang Y, et al. J Thorac Oncol. 2020;15:1636–1646.


3. Yang Y, et al. 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. Abstract 4MO. ELCC 2022 Virtual Meeting, 30 March–02 April.

 

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Posted on 25 May, 2022