Checkpoint Inhibitors in Metastatic EGFR- Mutated Non–Small Cell Lung Cancer—A Meta-Analysis

Lee, Chee Khoon; Man, Johnathan; Lord, Sarah J.; Links, Matthew; Gebski, Val; Mok, Tony; Yang, James Chih‐Hsin

doi:10.1016/j.jtho.2016.10.007

Cited by 684 publications

(512 citation statements)

References 15 publications

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“…All the above-mentioned biological knowledge and preclinical evidence indicates that the benefit from ICB in NSCLC patients with EGFR mutations or EML4-ALK rearrangements is doubtful. Indeed the subgroup analyses from ICB clinical trials have shown no benefit from anti-PD-1/L1 antibodies in NSCLC patients with EGFR mutations (52,53). In a retrospective analysis, the objective response to anti-PD-1/L1 antibodies was 3.6% for EGFR mutant and ALK rearranged NSCLC patients compared to 23.3% for EGFR and ALK wild type or those with unknown status (42).…”

Section: Introductionmentioning

confidence: 99%

The combination of checkpoint immunotherapy and targeted therapy in cancer

Karachaliou¹,

Cao²,

Sosa³

et al. 2017

Ann. Transl. Med.

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Abstract:The therapeutic possibilities for patients with metastatic melanoma have changed due to the development of targeted therapies that inhibit oncogenic signaling pathways as well as immune modulating therapies that unleash the patient antitumor immunity. These therapeutic changes have impressively increased the median overall survival of the patients. Considering the dramatic but transient responses that occur with targeted therapies for a subgroup of patients and the durable responses that can be achieved with immunotherapy in a subset of patients, a lot of effort is ongoing for the clinical development of combinations of these two therapeutic approaches. Herein we discuss the existing preclinical and clinical data for the combination of targeted therapies and immunotherapy focusing mainly on melanoma and non-small cell lung cancer (NSCLC).

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Section: Introductionmentioning

confidence: 99%

The combination of checkpoint immunotherapy and targeted therapy in cancer

Karachaliou¹,

Cao²,

Sosa³

et al. 2017

Ann. Transl. Med.

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“…However the majority of clinical trials of immunecheckpoint inhibitors (ICI) in lung cancer have shown that single agent ICIs are not effective in pre-treated NSCLC patients harboring EGFR-mutations, discouraging their clinical use in this subgroup of patients. A recent meta-analysis also confirmed that PD1/PDL1 inhibitors don't improve OS compared to docetaxel in pre-treated, EGFR-mutated NSCLC patients (Lee et al, 2017 Feb). Translational studies clearly demonstrated that NSCLC with oncogene drivers, including both EGFR activating and resistant mutations, are characterized by a very low tumor mutation burden (TMB), which is commonly considered as good predictor of response to ICI therapy (Spigel et al, 2016;Rizvi et al, 2015).…”

Section: Immunotherapymentioning

confidence: 95%

EGFR inhibition in NSCLC: New findings…. and opened questions?

Passiglia

Listì

Castiglia

et al. 2017

Critical Reviews in Oncology/Hematology

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The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients’ outcomes. In this review we summarize the most important recent findings regarding EGFR-inhibition in NSCLC, highlighting the current unsolved questions on the selection of the best TKI in first-line, which therapy can be combined with upfront EGFR-TKIs, how to overcome acquired resistance, and which are the clinical applications of liquid biopsy

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Section: Immunotherapeutics and Patient Selectionmentioning

confidence: 99%

“…For example, the use of epidermal growth factor receptor (EGFR) TKIs is standard of care in patients with EGFR-mutation-positive NSCLC [92][93][94], and studies suggest that this population may not derive benefit from immunotherapy versus EGFR TKIs [95] or chemotherapy [96]. Therefore, the clinical benefit from monotherapy with anti-PD-1/PD-L1 antibodies remains suboptimal in EGFR-mutation-positive NSCLC, and novel combination and therapeutic approaches are needed [96]. The approval of anti-PD-1 therapy for the treatment of adult and pediatric patients with MSI-H or dMMR solid tumors (pembrolizumab) or colorectal cancer (pembrolizumab and nivolumab) that has progressed, underscores the importance of considering other biomarkers that are not specific to the immune checkpoint pathway when making ICB therapy decisions [13].…”

Section: Immunotherapeutics and Patient Selectionmentioning

confidence: 99%

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

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Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival. Immunotherapies function through modulation of the immune system, which can lead to immune-mediated adverse events (imAEs). These include a range of dermatologic, gastrointestinal, endocrine, and hepatic toxicities, as well as other less common inflammatory events. ImAEs are typically low grade and manageable when identified early and treated with appropriate measures. Identifying the right patient for the right therapy will become more important as new immunotherapies and immunotherapy-based combinations are approved and costs of cancer care continue to rise.

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Checkpoint Inhibitors in Metastatic EGFR- Mutated Non–Small Cell Lung Cancer—A Meta-Analysis

Abstract: In EGFR-mutant advanced NSCLC, immune checkpoint inhibitors do not improve OS over that with docetaxel. Mechanisms of acquired resistance to first-line tyrosine kinase inhibitor therapy should be elucidated to guide selection of second-line treatment for these patients.

Cited by 684 publications

References 15 publications

The combination of checkpoint immunotherapy and targeted therapy in cancer

The combination of checkpoint immunotherapy and targeted therapy in cancer

EGFR inhibition in NSCLC: New findings…. and opened questions?

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

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