Multi‐target angiogenesis inhibitor combined with <scp>PD</scp>‐1 inhibitors may benefit advanced non‐small cell lung cancer patients in late line after failure of <scp>EGFR‐TKI</scp> therapy

Yu, Lian; Hu, Yaohua; Xu, Jianlin; Qiao, Rong; Han, Baohui; Xia, Jinjing; Zhong, Runbo

doi:10.1002/ijc.34536

Cited by 13 publications

(12 citation statements)

References 34 publications

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“…However, cabozantinib plus atezolizumab only demonstrated modest activity in 30 patients with previously‐treated advanced EGFR ‐mutated NSCLC (ORR = 7%, DCR = 63%, median PFS = 2.7 months, and median OS = 6.1 months) 35 . In contrast, anlotinib combined with ICIs exhibited a longer median PFS (4.3 months vs 3.6 months, p = 0.005), and OS (14.2 months vs 9.0 months p = 0.029) than chemotherapy for the late‐line treatment of patients with NSCLC and EGFR‐TKI resistance 36 . Additionally, the phase 3 Orient‐31 trial reported that sintilimab plus the bevacizumab biosimilar IBI305 and chemotherapy led to significant improvements in PFS over chemotherapy alone in patients with advanced EGFR ‐mutated NSCLC after TKI failure (6.9 vs 4.3 months; p < 0.001) 37 .…”

Section: Discussionmentioning

confidence: 98%

Sintilimab plus anlotinib as second‐ or third‐line therapy in metastatic non‐small cell lung cancer with uncommon epidermal growth factor receptor mutations: A prospective, single‐arm, phase II trial

Chen,

Xu,

Huang

et al. 2023

Cancer Medicine

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BackgroundPatients with non‐small‐cell lung cancer (NSCLC) and uncommon EGFR alterations typically have worse treatment outcomes than patients with classically EGFR‐mutated NSCLC. This study aimed to investigate the efficacy and safety of PD‐1 blockade with sintilimab plus anti‐angiogenic treatment with anlotinib in patients with NSCLC harboring uncommon EGFR mutations.MethodsPatients with metastatic NSCLC harboring uncommon EGFR mutations after two previous treatments, including a platinum‐based chemotherapy regimen and a targeted treatment (or chemotherapy only for patients harboring EGFR ex20ins), received sintilimab combined with anlotinib. The primary endpoint was objective response rate (ORR).ResultsAt data cutoff (September 27, 2022), median follow‐up was 22.3 months (range, 1.2–37.6). Among 21 enrolled patients, 12 had EGFR ex20ins and nine had other uncommon EGFR mutations such as L861Q, G719A, and G709X. Overall, eight patients (38.1%) achieved an objective response, and 18 (85.7%) achieved disease control. Median (95% CI) progression‐free survival (PFS) was 7.0 (5.4–8.6) months, and median overall survival (OS) was 20.0 (15.6–24.4) months. The 12‐month PFS rate (95% CI) was 22.2% (7.4–42.0), and the 12‐month OS rate was 66.7% (42.5–82.5). Patients harboring EGFR ex20ins had similar ORR and PFS to those with other mutations. Six patients (28.6%) experienced grade 3 treatment‐related adverse events (TRAEs); hand‐foot syndrome was the most common grade 3 TRAE (2 patients; 9.5%). No grade ≥4 TRAEs were observed.ConclusionsThe combination of sintilimab and anlotinib demonstrated durable efficacy and was generally well tolerated in patients with NSCLC and uncommon EGFR mutations who had received prior standard‐of‐care treatments. (ClinicalTrials.gov identifier: NCT04790409).

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Section: Discussionmentioning

confidence: 98%

Sintilimab plus anlotinib as second‐ or third‐line therapy in metastatic non‐small cell lung cancer with uncommon epidermal growth factor receptor mutations: A prospective, single‐arm, phase II trial

Chen,

Xu,

Huang

et al. 2023

Cancer Medicine

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“…Several studies have demonstrated that immunotherapy shows clinical activity in LUAD [ 49 , 50 ]. In this research, the risk scores are highly correlated with immune checkpoint expression, including HAVCR2 and CTLA4.…”

Section: Discussionmentioning

confidence: 99%

Molecular subgroup establishment and signature creation of lncRNAs associated with acetylation in lung adenocarcinoma

Chen,

Wang,

Shao

et al. 2024

Aging

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Background: The significance of long non-coding RNAs (lncRNAs) as pivotal mediators of histone acetylation and their influential role in predicting the prognosis of lung adenocarcinoma (LUAD) has been increasingly recognized. However, there remains uncertainty regarding the potential utility of acetylation-related lncRNAs (ARLs) in prognosticating the overall survival (OS) of LUAD specimens. Methods: The RNA-Seq and clinical information were downloaded from The Cancer Genome Atlas (TCGA). Through the differential analysis, weighted correlation network analysis (WGCNA), Pearson correlation test and univariate Cox regression, we found out the prognosis associated ARLs and divided LUAD specimens into two molecular subclasses. The ARLs were employed to construct a unique signature through the implementation of the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. Subsequently, the predictive performance was evaluated using ROC analysis and Kaplan-Meier survival curve analysis. Finally, ARL expression in LUAD was confirmed by quantitative real-time PCR (qRT-PCR). Results: We triumphantly built a ARLs prognostic model with excellent predictive accuracy for LUAD. Univariate and multivariate Cox analysis illustrated that risk model served as an independent predictor for influencing the overall survival OS of LUAD. Furthermore, a nomogram exhibited strong prognostic validity. Additionally, variations were observed among subgroups in the field of immunity, biological functions, drug sensitivity and gene mutations within the field. Conclusions: Nine ARLs were identified as promising indicators of personalized prognosis and drug selection for people suffering with LUAD.

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“…In the IMpower 150 trial, the combination of ICIs, bevacizumab, and chemotherapy showed an advantage as a first-line treatment for nonsquamous NSCLC ( 27 ). Some studies have found good results with the combination of anlotinib and ICIs in a variety of tumors, including lung cancer ( 16 , 19 , 28 , 29 ). Our study found superior efficacy of anlotinib and PD-1 blockade combination therapy as second- and subsequent-line treatment of patients with advanced driver-negative LUAD, a subset of patients that few studies have focused on.…”

Section: Discussionmentioning

confidence: 99%

“…Combination strategy of anti-angiogenesis inhibitor and ICIs could counteract the immunosuppression, exerting synergistic antitumor effects. The efficacy and safety of anlotinib and ICIs combination therapy has been validated in several solid tumors, including advanced NSCLC as first-line treatment ( 16 - 19 ). This retrospective study aimed to explore the efficacy and safety of anlotinib and ICIs as a second- and subsequent-line treatment for advanced lung adenocarcinoma (LUAD) in patients without oncogenic driver alterations.…”

Section: Introductionmentioning

confidence: 99%

Comparative efficacy and safety of multitarget angiogenesis inhibitor combined with immune checkpoint inhibitor and nivolumab monotherapy as second-line or beyond for advanced lung adenocarcinoma in driver-negative patients: a retrospective comparative cohort study

Yu¹,

Xu²,

Qiao³

et al. 2023

Transl Lung Cancer Res

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Background The efficacy of immune monotherapy is not satisfactory in patients with advanced, treated non-small cell lung cancer (NSCLC). Combining antiangiogenic agents and immune checkpoint inhibitors (ICIs) can counteract the immunosuppression and confer synergistic therapeutic benefits. We explored the efficacy and safety of anlotinib and ICIs as a second- and subsequent-line treatment for advanced lung adenocarcinoma (LUAD) in patients without oncogenic driver alterations. Methods We reviewed patients with driver-negative LUAD who had received anlotinib, a multityrosine kinase inhibitor affecting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit, in combination with ICIs from October 2018 to July 2021 at Shanghai Chest Hospital as second- and subsequent-line treatment. Patients with advanced driver-negative LUAD who received nivolumab monotherapy as second-line treatment were included as a control group. Results In this study, 71 patients were included who had received anlotinib and programmed cell death-1 (PD-1) blockade combination therapy as second- and subsequent-line treatment, and 63 patients who had received nivolumab monotherapy as second-line therapy were included as controls, most of whom were male smokers at stage IV. The median progression-free survival (PFS) of the combination therapy and nivolumab monotherapy groups were 6.00 and 3.41 months, respectively (P<0.001). The median overall survival (OS) of the combination therapy and nivolumab monotherapy groups were 16.13 and 11.88 months, respectively (P=0.046). Twenty-nine patients (40.8%) in the combination group underwent previous immunotherapy (15 of whom were in first line), and they also achieved good survival (median OS: 25.67 months). The adverse reactions in the combination therapy group were mainly associated with either anlotinib or ICI administration, and there was a low incidence of grade 3 adverse events, all of which were resolved after intervention or discontinuation. Conclusions The combination of the multitargeting tyrosine kinase inhibitor anlotinib and PD-1 blockade demonstrated significant benefits as the second- and subsequent-line treatment in driver-negative patients with advanced LUAD, even in those who underwent previous immunotherapy.

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Multi‐target angiogenesis inhibitor combined with PD‐1 inhibitors may benefit advanced non‐small cell lung cancer patients in late line after failure of EGFR‐TKI therapy

Cited by 13 publications

References 34 publications

Sintilimab plus anlotinib as second‐ or third‐line therapy in metastatic non‐small cell lung cancer with uncommon epidermal growth factor receptor mutations: A prospective, single‐arm, phase II trial

Sintilimab plus anlotinib as second‐ or third‐line therapy in metastatic non‐small cell lung cancer with uncommon epidermal growth factor receptor mutations: A prospective, single‐arm, phase II trial

Molecular subgroup establishment and signature creation of lncRNAs associated with acetylation in lung adenocarcinoma

Comparative efficacy and safety of multitarget angiogenesis inhibitor combined with immune checkpoint inhibitor and nivolumab monotherapy as second-line or beyond for advanced lung adenocarcinoma in driver-negative patients: a retrospective comparative cohort study

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