VP9-2021: ORIENT-31: Phase III study of sintilimab with or without IBI305 plus chemotherapy in patients with EGFR mutated nonsquamous NSCLC who progressed after EGFR-TKI therapy

Lu, Shun; Wu, Lin; Hong, Jian; Cheng, Ying; Wang, Q.; Fang, Jian; Wang, Z.; Hu, Yang; Sun, Meili; Han, Liang; Miao, Liyun; Ding, Cuimin; Cui, Jiuwei; Li, B.; Li, X.; Wang, K.; Cang, Shundong; Pan, Yueyin; Ye, F.; Liu, A.

doi:10.1016/j.annonc.2021.10.007

Cited by 31 publications

(25 citation statements)

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“…The data from the IMpower150 study suggested an improvement in PFS and OS with the ABCP regimen in EGFR-TKI-resistant NSCLC patients compared to the BCP regimen. Recently, the interim analysis of a phase III ORIENT-31 study demonstrated a significant improvement in mPFS (6.9 vs. 4.3 months) and ORR (44% vs. 25%) with the combination of sintilimab, bevacizumab, pemetrexed and cisplatin compared to pemetrexed plus cisplatin in EGFR-TKI-resistant patients, which further confirms the role of antiangiogenic agents with ICI combined with chemotherapy in EGFR-TKI-resistant patients (Lu et al, 2022). A final OS analysis is eagerly awaited to confirm whether the PFS improvement can translate into a long-term survival benefit.…”

Section: Figurementioning

confidence: 78%

“…Different studies have investigated the combinations of ICIs and antiangiogenic inhibitors, including both monoclonal antibodies (mAbs) targeting VEGF/VEGFR, such as bevacizumab and ramucirumab, and small molecule tyrosine kinase inhibitors (TKIs) ( Gadgeel et al, 2018 ; Reck et al, 2019b ; Herbst et al, 2019 ; Zhou et al, 2019 ; Bang et al, 2020 ; Herbst et al, 2020 ; Lee et al, 2020 ; Nishio et al, 2020 ; Seto et al, 2020 ; Taylor et al, 2020 ; Zhou et al, 2020 ; Han et al, 2021a ; Ardeshir-Larijani et al, 2021 ; Han et al, 2021b ; Chu et al, 2021 ; Gao et al, 2021 ; Leal et al, 2021 ; Neal et al, 2021 ; Yang et al, 2021 ; Gao et al, 2022 ; Lee et al, 2022 ; Lu et al, 2022 ; Ren et al, 2022 ). However, the reported studies to date are mostly single-arm or retrospective studies with limited patient enrollment and heterogeneous results.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of combined immunotherapy and antiangiogenesis with or without chemotherapy for advanced non-small-cell lung cancer: A systematic review and pooled analysis from 23 prospective studies

Gao

Song²,

Sun³

et al. 2022

Front. Pharmacol.

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Purpose: Immune checkpoint and antiangiogenic inhibitors have a potentially synergistic antitumor effect. We aimed to assess the efficacy and safety of immunotherapy in combination with antiangiogenesis therapy with or without chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).Methods: PubMed, Embase, the Cochrane library, Google Scholar, Ovid, Scopus, and Web of Science were searched for eligible trials. ClinicalTrials.gov and meeting abstracts were also searched for qualified clinical studies. The inclusion criteria were as follows: prospective studies (including single-arm studies) that evaluated efficacy and/or toxicity of immunotherapy combined with antiangiogenic agents (A + I) with or without chemotherapy (A + I + chemo) in patients with advanced or metastatic NSCLC; and primary outcome of each study reported at least one of these endpoints: progression-free survival (PFS), overall survival, objective response rate (ORR), disease control rate (DCR), or adverse events (AEs).Results: Twenty three prospective studies comprising 1,856 patients with advanced NSCLC were included. The pooled ORR, median PFS and estimated overall survival were 39%, 6.8 months [95% confidence interval (CI), 5.53–8.13], and 18.6 months in the overall group. Similar ORR and median PFS with A + I + chemo versus A + I were observed in patients treated in first-line setting [59% and 9.47 months (95% CI, 6.45–12.49) versus 52% and 10.9 months (95% CI, 1.81–19.98), respectively]. We also observed improved ORR and mPFS with A + I + chemo versus A + I in subsequent-line setting [56% and 8.1 months (95% CI, 5.00–11.26) versus 22% and 5.1 months (95% CI, 4.01–6.15), respectively]. Efficacy of A + I + chemo therapy was evident across different PD-L1 subgroups, especially in patients with EGFR mutations [ORR: 59%; mPFS: 8.13 months (95% CI: 5.00–11.26)] or baseline liver metastases. The incidence of AEs with a major grade of ≥3 in the overall, A + I, and A + I + chemo groups were 4.1% vs. 5.5% vs. 3.4% for proteinuria, 13.7% vs. 16.2% vs. 9.7% for hypertension, and 1.9% vs. 1.2% vs. 2.8% for rash, respectively. No new safety signals were identified in this pooled analysis.Conclusion: Immunotherapy combined with antiangiogenic agents with or without chemotherapy showed encouraging antitumor activity and an acceptable toxicity profile in treatment-naïve or pretreated patients with advanced NSCLC. Doublet treatment with immunotherapy and antiangiogenic agents might be a new option for patients with advanced NSCLC, especially those who are treatment-naive or cannot tolerate chemotherapy.

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Section: Figurementioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of combined immunotherapy and antiangiogenesis with or without chemotherapy for advanced non-small-cell lung cancer: A systematic review and pooled analysis from 23 prospective studies

Gao

Song²,

Sun³

et al. 2022

Front. Pharmacol.

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“…Another similar quadruplet that bears promising early results is currently being investigated in the phase III ORIENT-31 trial. Sintilimab, a novel anti-PD-1 agent with or without IBI305, a biosimilar of bevacizumab, plus chemotherapy in EGFRm NSCLC after progression on EGFR-TKI significantly prolonged mPFS (6.9 versus 4.3 months; HR 0.464, 95% CI: 0.337, 0.639; p < 0.0001) and increased ORR (43.9 versus 25.2%) in comparison with chemotherapy alone [ 175 ].…”

Section: Resultsmentioning

confidence: 99%

Resistance to TKIs in EGFR-Mutated Non-Small Cell Lung Cancer: From Mechanisms to New Therapeutic Strategies

Koulouris

Tsagkaris

Corriero

et al. 2022

Cancers

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Resistance to tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) in advanced mutant Non-Small Cell Lung Cancer (NSCLC) constitutes a therapeutic challenge. This review intends to summarize the existing knowledge about the mechanisms of resistance to TKIs in the context of EGFR mutant NSCLC and discuss its clinical and therapeutic implications. EGFR-dependent and independent molecular pathways have the potential to overcome or circumvent the activity of EGFR-targeted agents including the third-generation TKI, osimertinib, negatively impacting clinical outcomes. CNS metastases occur frequently in patients on EGFR-TKIs, due to the inability of first and second-generation agents to overcome both the BBB and the acquired resistance of cancer cells in the CNS. Newer-generation TKIs, TKIs targeting EGFR-independent resistance mechanisms, bispecific antibodies and antibody-drug conjugates or combinations of TKIs with other TKIs or chemotherapy, immunotherapy and Anti–Vascular Endothelial Growth Factors (anti-VEGFs) are currently in use or under investigation in EGFR mutant NSCLC. Liquid biopsies detecting mutant cell-free DNA (cfDNA) provide a window of opportunity to attack mutant clones before they become clinically apparent. Overall, EGFR TKIs-resistant NSCLC constitutes a multifaceted therapeutic challenge. Mapping its underlying mutational landscape, accelerating the detection of resistance mechanisms and diversifying treatment strategies are essential for the management of the disease.

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“…Lastly, ORIENT-31 is an ongoing phase 3, randomized, double-blind trial investigating the anti-PD-1 antibody sintilimab, with or without the bevacizumab biosimilar IBI305, plus pemetrexed and cisplatin chemotherapy in patients with EGFRm NSCLC who progressed after EGFR-TKI therapy (NCT03802240). Preliminary results (median follow-up 9.8 months) found median PFS was 6.9 months with combination therapy sintilimab/IBI305/pemetrexed/ cisplatin compared with 4.3 months in patients receiving pemetrexed/ cisplatin; ORR also improved in the combination therapy group vs the chemotherapy only group [86,87].…”

Section: Angiogenesis Inhibitors For Egfr-mutated Nsclcmentioning

confidence: 98%

Treatment strategies and outcomes for patients with EGFR-mutant non-small cell lung cancer resistant to EGFR tyrosine kinase inhibitors: Focus on novel therapies

et al. 2022

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VP9-2021: ORIENT-31: Phase III study of sintilimab with or without IBI305 plus chemotherapy in patients with EGFR mutated nonsquamous NSCLC who progressed after EGFR-TKI therapy

Cited by 31 publications

References 0 publications

Efficacy and safety of combined immunotherapy and antiangiogenesis with or without chemotherapy for advanced non-small-cell lung cancer: A systematic review and pooled analysis from 23 prospective studies

Efficacy and safety of combined immunotherapy and antiangiogenesis with or without chemotherapy for advanced non-small-cell lung cancer: A systematic review and pooled analysis from 23 prospective studies

Resistance to TKIs in EGFR-Mutated Non-Small Cell Lung Cancer: From Mechanisms to New Therapeutic Strategies

Treatment strategies and outcomes for patients with EGFR-mutant non-small cell lung cancer resistant to EGFR tyrosine kinase inhibitors: Focus on novel therapies

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