Long-term comparative efficacy and safety of nivolumab plus ipilimumab relative to other first-line therapies for advanced non-small-cell lung cancer: A systematic literature review and network meta-analysis

O’Byrne, Kenneth J.; Popoff, Evan; Badin, Firas; Lee, Adam F.; Yuan, Yong; Lozano‐Ortega, Greta; Eccles, Laura J.; Varol, N.; Waser, Nathalie; Penrod, John R.; Goring, Sarah

doi:10.1016/j.lungcan.2023.01.006

Cited by 11 publications

(6 citation statements)

References 47 publications

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“…The underlying mechanism may relate to the strength of the immune response to self-antigens-eventually leading to the occurrence of irAEs-and the robustness of the T-cell immune response to cancer-associated antigens. This enhanced T-cell immune response has been corroborated in a recent meta-analysis 27 comparing the e cacy of NIVO and IPI combination therapy to ICI plus chemotherapy in the long term. This analysis revealed a higher occurrence of Grade ≥ 3 irAEs in patients receiving NIVO and IPI compared with pembrolizumab monotherapy, whereas there were no reported cases of CRS among patients receiving the combination of NIVO and IPI, as observed in the NIPPON study, in global phase III trials investigating this combination for advanced NSCLC 14,15 .…”

Section: Discussionmentioning

confidence: 66%

Clinical Association Between Immune-Related Adverse Events and Treatment Efficacy in Non-Small Cell Lung Cancer Patients Treated with Nivolumab plus Ipilimumab-Based Therapy

Ebi,

Inoue,

Igata

et al. 2024

Preprint

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Nivolumab and ipilimumab combination therapy, explored for advanced non-small cell lung cancer (NSCLC) in trials like CheckMate 227 and CheckMate 9LA, raises questions about the relationship between immune-related adverse events (irAEs) and treatment efficacy in real-world settings. In our retrospective analysis of 28 advanced or recurrent NSCLC patients treated with nivolumab plus ipilimumab (with/without platinum-doublet chemotherapy) from February 2021 to January 2023, we aimed to understand the clinical association between irAEs and treatment efficacy. Among the 28 patients, 22 (78.6%) experienced irAEs. Patients with irAEs demonstrated significantly longer median progression-free survival (PFS) and overall survival (OS) than those without (P = 0.0158 and P = 0.000394, respectively). irAE severity did not significantly influence PFS or OS. The objective response rate was higher in patients with irAEs than those without (50.0% versus 0.0%, P = 0.0549). Multivariate analysis identified irAE occurrence as an independent factor for PFS (hazard ratio = 0.2084, P = 0.01383) and OS (hazard ratio = 0.0857, P = 0.001588). Interstitial lung disease was inferior to other irAE profiles for both PFS and OS. In conclusion, advanced NSCLC patients experiencing irAEs demonstrated superior clinical outcomes with nivolumab plus ipilimumab-based therapy, though interstitial lung disease may be less linked with PFS and OS than other irAE profiles.

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Section: Discussionmentioning

confidence: 66%

Clinical Association Between Immune-Related Adverse Events and Treatment Efficacy in Non-Small Cell Lung Cancer Patients Treated with Nivolumab plus Ipilimumab-Based Therapy

Ebi,

Inoue,

Igata

et al. 2024

Preprint

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“…that the combination outperforms nivolumab monotherapy in terms of ORR and DCR, however patients may experience increased AEs [36]. One particular instance where using Ipilimumab+Nivolumab has been clearly demonstrated in multiple meta-analyses to result in improved ORR response [37][38][39]. Ipilimumab+Nivolumab use, however, still requires cautious consideration because of the possibility of excessive adverse effects.…”

Section: Discussionmentioning

confidence: 99%

The Efficacy and Safety of Pembrolizumab, Ipilimumab, and Nivolumab Monoteraphy and Combination for Colorectal Cancer: A Systematic Review and Meta-Analysis

Adrianto,

Riwanto,

Sadhana

et al. 2024

Preprint

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BackgroundColorectal cancer (CRC) ranks third globally in cancer-related mortality, with rising incidence, particularly in Asia, projecting a 60% surge by 2030. Metastatic CRC (mCRC) presents a significant challenge with a grim 5-year survival rate of 14%. Emerging evidence suggests that tumors with DNA mismatch repair deficiency (dMMR) and high microsatellite instability (MSI-H) respond well to immune checkpoint inhibitors (ICIs), marking a paradigm shift in therapeutic approaches. This systematic review and meta-analysis aim to comprehensively assess Pembrolizumab, Nivolumab, and the combination of Nivolumab and Ipilimumab in advanced CRC, considering their significant antitumor efficacy in MSI-H/dMMR mCRC.MethodsFollowing PRISMA guidelines and Cochrane Handbook standards, this study covers 2014 to 2024, involving advanced CRC patients treated with ICIs. A comprehensive literature search employed 12 independent authors across eight databases. Parameters such as overall survival, progression-free survival, and objective response rate were extracted.The Cochrane Collaboration’s Risk of Bias version 2 tool assessed risk. Statistical analysis utilized mean difference and risk ratios with random-effect models due to anticipated heterogeneity. Robustness was ensured through publication bias analysis and sensitivity meta-analysis. Linear regression explored associations in subgroup analysis.ResultsThe meta-analysis evaluated ORR and OS across different immunotherapy interventions. Nivolumab, Nivolumab+Ipilimumab, and Pembrolizumab exhibited varying ORR and OS effect sizes with corresponding heterogeneity levels. Progression-free survival (PFS) analysis also showed diverse effect sizes and heterogeneity levels across the three interventions. The study provides a comprehensive overview of response rates and survival outcomes for these immunotherapies in advanced CRC.ConclusionsThe study concludes that combination immunotherapy, particularly Nivolumab and Ipilimumab, presents a promising avenue for advanced CRC treatment, showing superior efficacy. Pembrolizumab monotherapy also exhibited promise. While the study offers valuable insights, the identified heterogeneity emphasizes the need for additional research. Adverse effects were generally low, supporting the viability of the studied immunotherapies. The study acknowledges limitations and calls for ongoing investigation to refine and validate these findings, marking a pioneering effort in systematically comparing short-term and long-term effects of anti-CTLA-4 and anti-PD-1 therapies in CRC.

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“…After all, how we interpret the results of an experiment (clinical trial or basic research) depends on the design of the experiments to test a hypothesis, which may or may not be correct or relevant. Again, the answers we receive often depend on the questions we pose, and the results we obtain depend on the hypotheses we formulate, no matter what tools (e.g., statistics) we use [ 87 , 90 ].…”

Section: Checkpoint Inhibitors Are Not Equalmentioning

confidence: 99%

Stem Cell Origin of Cancer: Clinical Implications beyond Immunotherapy for Drug versus Therapy Development in Cancer Care

Tu,

Trikannad,

Vellanki

et al. 2024

Cancers

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Although immunotherapy has revolutionized cancer care, there is still an urgent need to enhance its efficacy and ensure its safety. A correct cancer theory and proper scientific method empower pertinent cancer research and enable effective and efficient drug versus therapy development for patient care. In this perspective, we revisit the concept of immune privilege in a cancer cell versus normal cell, as well as in a cancer stem cell versus normal stem cell. We re-examine whether effective immunotherapies are efficacious due to their anti-cancer and/or immune modulatory mechanisms. We reassess why checkpoint inhibitors (CPIs) are not equal. We reconsider whether one can attribute the utility of immunotherapy to specific cancer subtypes and its futility to certain tumor/immune compartments, components, and microenvironments. We propose ways and means to advance immunotherapy beyond CPIs by combining anti-PD1/L1 with various other treatment modalities according to an appropriate scientific theory, e.g., stem cell origin of cancer, and based on available clinical evidence, e.g., randomized clinical trials. We predict that a stem cell theory of cancer will facilitate the design of better and safer immunotherapy with improved selection of its use for the right patient with the right cancer type at the right time to optimize clinical benefits and minimize potential toxic effects and complications.

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Long-term comparative efficacy and safety of nivolumab plus ipilimumab relative to other first-line therapies for advanced non-small-cell lung cancer: A systematic literature review and network meta-analysis

Cited by 11 publications

References 47 publications

Clinical Association Between Immune-Related Adverse Events and Treatment Efficacy in Non-Small Cell Lung Cancer Patients Treated with Nivolumab plus Ipilimumab-Based Therapy

Clinical Association Between Immune-Related Adverse Events and Treatment Efficacy in Non-Small Cell Lung Cancer Patients Treated with Nivolumab plus Ipilimumab-Based Therapy

The Efficacy and Safety of Pembrolizumab, Ipilimumab, and Nivolumab Monoteraphy and Combination for Colorectal Cancer: A Systematic Review and Meta-Analysis

Stem Cell Origin of Cancer: Clinical Implications beyond Immunotherapy for Drug versus Therapy Development in Cancer Care

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