&lt;p&gt;A Review About Pembrolizumab in First-Line Treatment of Advanced NSCLC: Focus on KEYNOTE Studies&lt;/p&gt;

Qu, Jing; Wang, Li; Jiang, Man; Zhao, Delong; Wang, Yuyang; Zhang, Feng; Li, Jing; Zhang, Xiaochun

doi:10.2147/cmar.s257188

Cited by 26 publications

(28 citation statements)

References 124 publications

(132 reference statements)

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“…In addition to pembrolizumab and atezolizumab, which were developed by multinational corporations (55,56), three locally developed PD-1 inhibitors (camrelizumab, tislelizumab, and sintilimab) are also available in China (31,48,(57)(58)(59). 2) (9,67,68). Some of the trials were conducted only in China, and some were international multicenter clinical trials that involved Chinese sites (69).…”

Section: Current Nsclc Immunotherapy Landscapementioning

confidence: 99%

“…Mounting evidence from randomized controlled trials has confirmed that, compared with platinum-based chemotherapy, ICIs provide better clinical outcomes in patients with advanced NSCLC ( Table 2 ) ( 9 , 67 , 68 ). Some of the trials were conducted only in China, and some were international multicenter clinical trials that involved Chinese sites ( 69 ).…”

Section: Ici As First-line Therapy For Advanced Nsclcmentioning

confidence: 99%

“…Immune checkpoints are key molecules in maintaining immune homeostasis and preventing tissue damage due to excessive or prolonged immune system activation. Thus, ICIs can induce various immune-related adverse events (IRAEs) ( 68 ). The most commonly affected systems in patients experiencing IRAEs are the gastrointestinal, dermatological, and endocrine systems ( 68 ).…”

Section: Adverse Reactions Related To Icismentioning

confidence: 99%

“…Thus, ICIs can induce various immune-related adverse events (IRAEs) ( 68 ). The most commonly affected systems in patients experiencing IRAEs are the gastrointestinal, dermatological, and endocrine systems ( 68 ). The most common side effects of ICIs are rash and mucosal irritation, occurring in nearly 50% of patients ( 27 ).…”

Section: Adverse Reactions Related To Icismentioning

confidence: 99%

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Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China

2021

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Lung cancer causes significant morbidity and mortality in China and worldwide. In China, lung cancer accounts for nearly one-fourth of all cancer deaths. Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, accounting for approximately 80%–85% of all lung cancer cases. Immunotherapy with immune checkpoint inhibitors (ICIs) is revolutionizing the treatment of NSCLC. Immune checkpoint molecules, including PD-1/PD-L1 and CTLA-4, can suppress immune responses by delivering negative signals to T cells. By interfering with these immunosuppressive axes, ICIs unleash antitumor immune responses, ultimately eliminating cancer cells. ICIs have demonstrated promising antitumor efficacy in NSCLC, and mounting evidence supports the use of ICIs in treatment-naïve patients with advanced NSCLC. A comprehensive overview of current and emerging ICIs for the first-line treatment of NSCLC in China will facilitate a better understanding of NSCLC immunotherapy using ICIs and optimize the clinical use of ICIs in previously untreated Chinese patients with NSCLC. Herein, we review the efficacy and safety of currently approved and investigational ICIs as the first-line treatment of NSCLC in China. We also discuss the challenges limiting more widespread use of ICIs and future directions in the first-line treatment of NSCLC using ICIs.

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Section: Current Nsclc Immunotherapy Landscapementioning

confidence: 99%

Section: Ici As First-line Therapy For Advanced Nsclcmentioning

confidence: 99%

Section: Adverse Reactions Related To Icismentioning

confidence: 99%

Section: Adverse Reactions Related To Icismentioning

confidence: 99%

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Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China

2021

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“…Nowadays, immune checkpoint inhibitors (ICIs) have proven to be a major breakthrough achievement in cancer treatment in the past decade. Especially, ICIs have shown convincing efficacy and tolerable safety in monotherapies or combined treatments in NSCLC [ 5 , 6 ]. However, the objective response rate of ICIs is only about 17%, indicating that it could benefit only a limited subpopulation of patients [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Development of nomogram based on immune-related gene FGFR4 for advanced non-small cell lung cancer patients with sensitivity to immune checkpoint inhibitors

Wang

Ren

et al. 2021

J Transl Med

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Introduction Immune checkpoint inhibitors (ICIs) have become a frontier in the field of clinical technology for advanced non-small cell lung cancer (NSCLC). Currently, the predictive biomarker of ICIs mainly including the expression of PD-L1, TMB, TIICs, MMR and MSI-H. However, there are no official biomarkers to guide the treatment of ICIs and to determine the prognosis. Therefore, it is essential to explore a systematic nomogram to predict the prognosis of ICIs treatment in NSCLC Methods In this work, we obtained gene expression and clinical data of NSCLC patients from the TCGA database. Immune-related genes (IRGs) were downloaded from the ImmPort database. The detailed clinical annotation and response data of 240 advanced NSCLC patients who received ICIs treatment were obtained from the cBioPortal for Cancer Genomics. Kaplan–Meier survival analysis was used to perform survival analyses, and selected clinical variables to develop a novel nomogram. The prognostic significance of FGFR4 was validated by another cohort in cBioPortal for Cancer Genomics. Results 3% of the NSCLC patients harbored FGFR4 mutations. The mutation of FGFR4 were confirmed to be associated with PD-L1, and TMB. Patients harbored FGFR4 mutations were found to have a better prolonged progression-free survival (PFS) to ICIs treatment (FGFR4: P = 0.0209). Here, we built and verified a novel nomogram to predict the prognosis of ICIs treatment for NSCLC patients. Conclusion Our results showed that FGFR4 could serve as novel biomarkers to predict the prognosis of ICIs treatment of advanced NSCLC. Our systematic prognostic nomogram showed a great potential to predict the prognosis of ICIs for advanced NSCLC patients.

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Phase 1 dose escalation study of FGFR4 inhibitor in combination with pembrolizumab in advanced solid tumors patients

Cui

Jiang

et al. 2023

Cancer Medicine

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Inhibition of fibroblast growth factor (FGF) 19-FGF Receptor 4 (FGFR4) signaling demonstrates potent anticancer activity. EVER4010001 is a highly selective FGFR4 inhibitor and pembrolizumab is approved for the treatment of several solid tumors. This study determined the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), pharmacokinetics, safety, and preliminary efficacy of EVER4010001 plus pembrolizumab in patients with advanced solid tumors. Methods: This Phase 1, multicenter, open-label study enrolled 19 Asian-Chinese patients (57.9% male: median age 58 years) with advanced solid tumors. For "3+3" dose escalation, 3-6 patients received treatment at each dose level (EVER4010001 40, 60, 80, or 100 mg twice daily [BID] plus pembrolizumab 200 mg every 3 weeks).Results: At the data cutoff (August 12, 2021), no dose-limiting toxicities (DLTs) were reported at 40 mg-80 mg. At 100 mg, 2 (40.0%) patients had 3 DLTs within the 28-day DLT observation period after first administration. Median time to peak EVER4010001 concentration (T max ) was 0.55-1.03 hours. Mean terminal EVER4010001 half-life (T 1/2 ) was 4.00-4.92 hours. The area under the concentration-time curve (AUC 0-t ) and maximum observed concentration (C max ) ranged from 2370.87-5475.77 hour*ng/ml and 606.07-1348.86 ng/ml, respectively. The most common EVER4010001-related treatment-emergent adverse events were diarrhea (94.7%), increased aspartate aminotransferase (57.9%), and increased alanine aminotransferase (47.4%). Conclusion:Eighty milligrams BID was the MTD and RP2D for EVER4010001 plus pembrolizumab. Efficacy results were promising, and no new safety risks were reported, justifying the Phase 2 portion of this study.

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<p>A Review About Pembrolizumab in First-Line Treatment of Advanced NSCLC: Focus on KEYNOTE Studies</p>

Cited by 26 publications

References 124 publications

Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China

Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China

Development of nomogram based on immune-related gene FGFR4 for advanced non-small cell lung cancer patients with sensitivity to immune checkpoint inhibitors

Phase 1 dose escalation study of FGFR4 inhibitor in combination with pembrolizumab in advanced solid tumors patients

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