Promising outlook with sugemalimab in non-small-cell lung cancer.

Abstract

Anti-PD-L1 (durvalumab) immunotherapy after chemotherapy with external beam radiotherapy (ie, the PACIFIC regimen) is standard care for patients with unresectable stage III non-small-cell lung cancer (NSCLC). In the PACIFIC trial, 1 Faivre-Finn C Vicente D Kurata T et al. Four-year survival with durvalumab after chemoradiotherapy in stage III NSCLC—an update from the PACIFIC trial. J Thorac Oncol. 2021; 16: 860-867 Summary Full Text Full Text PDF PubMed Scopus (153) Google Scholar this regimen showed durable progression-free survival, with the estimated number of randomly assigned patients who remained alive at 4 years being 50% in the group that received 12 months of anti-PD-L1 consolidation therapy using durvalumab following chemotherapy plus concurrent radiotherapy versus 36% in patients who received placebo alone. Preclinical studies have shown that radiotherapy can boost anti-tumour immune response and overcome resistance to current immunotherapies. Clinical studies have shown improved responsiveness to pembrolizumab (anti-PD-1 antibody) in metastatic NSCLC, and to durvalumab (anti-PD-L1 antibody) in operable NSCLC. In the PEMBRO-RT and MDACC trials, 2 Theelen W Chen D Verma V et al. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med. 2021; 9: 467-475 Summary Full Text Full Text PDF PubMed Scopus (98) Google Scholar the best abscopal response (for non-irradiated lesions) was 20% with pembrolizumab versus 42% with pembrolizumab plus radiotherapy (odds ratio 2·96, 95% CI 1·42–6·20; p=0·0039). Median progression-free survival was 4·4 months (95% CI 2·9–5·9) with pembrolizumab alone versus 9·0 months (6·8–11·2) with pembrolizumab plus radiotherapy (hazard ratio [HR] 0·67, 95% CI 0·45–0·99; p=0·045). 2 Theelen W Chen D Verma V et al. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med. 2021; 9: 467-475 Summary Full Text Full Text PDF PubMed Scopus (98) Google Scholar In a phase 2 trial comparing neoadjuvant durvalumab alone versus neoadjuvant durvalumab plus stereotactic radiotherapy in patients with resectable early-stage NSCLC (clinical stages I–IIIA), a major pathological response was observed in 7% of the durvalumab alone group versus 53% of the durvalumab plus radiotherapy group. 3 Altorki NK McGraw TE Borczuk AC et al. Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial. Lancet Oncol. 2021; 22: 824-835 Summary Full Text Full Text PDF PubMed Scopus (59) Google Scholar Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trialSugemalimab plus chemotherapy showed a statistically significant and clinically meaningful progression-free survival improvement compared with placebo plus chemotherapy, in patients with previously untreated squamous and non-squamous metastatic NSCLC, regardless of PD-L1 expression, and could be a newfirst-line treatment option for both squamous and non-squamous metastatic NSCLC. Full-Text PDF Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trialSugemalimab after definitive concurrent or sequential chemoradiotherapy could be an effective consolidation therapy for patients with stage III NSCLC whose disease has not progressed after sequential or concurrent chemoradiotherapy. Longer follow-up is needed to confirm this conclusion. Full-Text PDF