Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial

Lü, Shun; Wu, Lin; Hong, Jian; Chen, Ying; Wang, Qiming; Fang, Jian; Wang, Ziping; Hu, Yanping; Sun, Meili; Liang, Huang; Miao, Liyun; Ding, Cuimin; Cui, Jiuwei; Li, Baolan; Pan, Yueyin; Li, Xingya; Ye, Feng; Liu, Anwen; Wang, Ke; Cang, Shundong; Zhou, Hui; Sun, Xiaofeng; Ferry, David; Lin, Yong; Wang, Shuyan; Zhang, Wen; Zhang, Chengli

doi:10.1016/s1470-2045(22)00382-5

Cited by 122 publications

(112 citation statements)

References 27 publications

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“…Nivolumab monotherapy has limited efficacy after EGFR–TKI resistance, with a mPFS of only 1.5–1.7 months [ 78 , 79 ]. In IMpower 150 and ORIENT-31 studies, EGFR–TKI resistance, followed by immunotherapy combined with bevacizumab and chemotherapy, showed a mPFS of 6.9–9.7 months but no subgroup data on MET amplification and/or c-MET overexpression was reported; meanwhile, safety of the combination therapy regimen needs attention [ 80 , 81 ]. MET -amplified and/or c-MET overexpressed advanced NSCLC patients with EGFR–TKI resistance have limited therapeutic effect with MET inhibitor monotherapy.…”

Section: Discussionmentioning

confidence: 99%

Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration—A Narrative Review

Zhu

Lu²,

Lü

2022

Cancers

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Non-small cell lung cancer (NSCLC) is increasingly being treated with targeted therapies. Savolitinib (Orpathys®) is highly selective mesenchymal epithelial transition (MET)–tyrosine kinase inhibitor (TKI), which is conditionally approved in China for advanced NSCLC with MET exon 14 skipping mutations (METex14). This article summarizes the clinical development of savolitinib, as a monotherapy in NSCLC with METex14 mutation and in combination with epidermal growth factor receptor (EGFR) inhibitor in post EGFR–TKI resistance NSCLC due to MET-based acquired resistance. Preclinical models demonstrated anti-tumor activities in MET-driven cancer cell line and xenograft tumor models. The Phase Ia/Ib study established an optimized, recommended phase II dose in Chinese NSCLC patients, while TATTON study of savolitinib plus osimertinib in patients with EGFR mutant, MET-amplified and TKI-progressed NSCLC showed beneficial efficacy with acceptable safety profile. In a pivotal phase II study, Chinese patients with pulmonary sarcomatoid carcinoma, brain metastasis and other NSCLC subtype positive for METex14 mutation showed notable responses and acceptable safety profile with savolitinib. Currently, results from ongoing clinical trials are eagerly anticipated to confirm the efficacious and safety benefits of savolitinib as monotherapy and in combination with EGFR–TKI in acquired resistance setting in advanced NSCLC and its subtypes with MET alterations.

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Section: Discussionmentioning

confidence: 99%

Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration—A Narrative Review

Zhu

Lu²,

Lü

2022

Cancers

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“…Similarly, another clinical trial showed that combination treatment with atezolizumab, bevacizumab, carboplatin and pemetrexed also achieved promising efficacy in metastatic EGFR-mutated NSCLC patients after EGFR-TKI failure [194]. Recently, interim results from the ORIENT-31 phase III trial (NCT03802240) indicated that PFS was significantly longer (6.9 months vs. 4.3 months) in the sintilimab plus IBI305 (bevacizumab biosimilar) plus cisplatin and pemetrexed group (SBCP regimen) than in the chemotherapy alone group in EGFR-mutated NSCLC patients who progressed on previous EGFR-TKIs therapy [195]. Taken together, these results suggest a synergistic effect of ICIs and antiangiogenic drugs on chemotherapy for the treatment of NSCLC patients in EGFR-mutated settings.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance

Xie

Wang

et al. 2022

J Hematol Oncol

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Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the preferential options for advanced non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. Osimertinib is a potent irreversible third-generation EGFR-TKI targeting EGFR mutations but has little effect on wild-type EGFR. In view of its remarkable efficacy and manageable safety, osimertinib was recommended as the standard first-line treatment for advanced or metastatic NSCLC patients with EGFR mutations. However, as the other EGFR-TKIs, osimertinib will inevitably develop acquired resistance, which limits its efficacy on the treatment of EGFR-mutated NSCLC patients. The etiology of triggering osimertinib resistance is complex including EGFR-dependent and EGFR-independent pathways, and different therapeutic strategies for the NSCLC patients with osimertinib resistance have been developed. Herein, we comprehensively summarized the resistance mechanisms of osimertinib and discuss in detail the potential therapeutic strategies for EGFR-mutated NSCLC patients suffering osimertinib resistance for the sake of the improvement of survival and further achievement of precise medicine.

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“… 9 Moreover, clinical trials provided strong evidence of programmed cell death ligand-1 (PD-(L)1) blockade and chemotherapy plus anti-angiogenesis as a new therapeutic strategy in EGFR-TKI-resistant patients. 10 , 11 Despite these triumphs, the majority of patients eventually failed to respond to immune checkpoint inhibitors (ICIs) therapy due to the evolution of primary or secondary resistance. Approximately, only 20–48% of patients with metastatic disease responded to ICIs 6 , 12 , 13 while the majority of them would eventually progress.…”

Section: Introductionmentioning

confidence: 99%

Treatment strategies based on different oligoprogressive patterns after immunotherapy failure in metastatic NSCLC

et al. 2023

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Background: Oligoprogressive disease is recognized as the overall umbrella term; however, a small number of progressions on imaging can represent different clinical scenarios. This study aims to explore the optimal treatment strategy after immunotherapy (IO) resistance in advanced non-small-cell lung cancer (NSCLC), especially in personalized therapies for patients with different oligoprogressive patterns. Methods: Based on European Society for Radiotherapy and Oncology/European Organization for Research and Treatment of Cancer consensus, metastatic NSCLC patients with cancer progression after IO resistance were divided into four patterns, repeat oligoprogression (REO, oligoprogression with a history of oligometastatic disease), induced oligoprogression (INO, oligoprogression with a history of polymetastatic disease), de-novo polyprogression (DNP, polyprogression with a history of oligometastatic disease), and repeat polyprogression (REP, polyprogression with a history of polymetastatic disease). Patients with advanced NSCLC who received programmed cell death-1/programmed cell death ligand-1 inhibitors between January 2016 and July 2021 at Shanghai Chest Hospital were identified. The progression patterns and next-line progression-free survival (nPFS), overall survival (OS) were investigated stratified by treatment strategies. nPFS and OS were calculated using the Kaplan–Meier method. Results: A total of 500 metastatic NSCLC patients were included. Among 401 patients developed progression, 36.2% (145/401) developed oligoprogression and 63.8% (256/401) developed polyprogression. Specifically, 26.9% (108/401) patients had REO, 9.2% (37/401) patients had INO, 27.4% (110/401) patients had DNP, and 36.4% (146/401) patients had REP, respectively. The patients with REO who received local ablative therapy (LAT) had significant longer median nPFS and OS compared with no LAT group (6.8 versus 3.3 months; p = 0.0135; OS, not reached versus 24.5 months; p = 0.0337). By contrast, there were no nPFS and OS differences in INO patients who received LAT compared with no LAT group (nPFS, 3.6 versus 5.3 months; p = 0.3540; OS, 36.6 versus 45.4 months; p = 0.8659). But in INO patients, there were significant longer median nPFS and OS using IO maintenance by contrast with IO halt treatment (nPFS, 6.1 versus 4.1 months; p = 0.0264; OS, 45.4 versus 32.3 months; p = 0.0348). Conclusions: LAT (radiation or surgery) is more important for patients with REO while IO maintenance plays a more dominant role in patients with INO.

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Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial

Cited by 122 publications

References 27 publications

Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration—A Narrative Review

Landscape of Savolitinib Development for the Treatment of Non-Small Cell Lung Cancer with MET Alteration—A Narrative Review

Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance

Treatment strategies based on different oligoprogressive patterns after immunotherapy failure in metastatic NSCLC

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