Improved Overall Survival and Locoregional Disease Control With Concurrent PD-1 Pathway Inhibitors and Stereotactic Radiosurgery for Lung Cancer Patients With Brain Metastases

Schapira, Emily; Hubbeling, Harper; Yeap, Beow Y.; Mehan, William A.; Shaw, Alice T.; Oh, Kevin; Gainor, Justin F.; Shih, Helen A.

doi:10.1016/j.ijrobp.2018.02.175

Cited by 106 publications

(90 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some argue that upfront systemic therapy in these patients addresses patients' intracranial and extracranial disease while also potentially sparing them from the neurotoxic effects of radiation therapy (RT) until intracranial disease progression. Others maintain that the risk of neurotoxicity from SRS is low and that BM‐directed therapy earlier in the course of treatment or, in the case of immunotherapy, combined with systemic therapy may result in better outcomes . Similar optimism existed for upfront the treatment of patients with BMs using EGFR‐TKi therapy; however, a large, multi‐institutional, retrospective study found that upfront SRS was independently associated with improved OS compared with upfront EGFR‐TKi therapy .…”

Section: Systemic Treatment Of Brain Metastasesmentioning

confidence: 99%

“…Others maintain that the risk of neurotoxicity from SRS is low and that BM-directed therapy earlier in the course of treatment or, in the case of immunotherapy, combined with systemic therapy may result in better outcomes. [53][54][55][56][57] Similar optimism existed for upfront the treatment of patients with BMs using EGFR-TKi therapy; however, a large, multi-institutional, retrospective study found that upfront SRS was independently associated with improved OS compared with upfront EGFR-TKi therapy. 41 Further research is required to better determine the efficacy and toxicity of combining immunotherapy with SRS and the optimal sequencing of treatment modalities.…”

Section: Summary On Systemic Therapiesmentioning

confidence: 99%

See 1 more Smart Citation

Current multidisciplinary management of brain metastases

Moravan

Fecci

Anders

et al. 2020

Cancer

View full text Add to dashboard Cite

Brain metastasis (BM), the most common adult brain tumor, develops in 20% to 40% of patients with late‐stage cancer and traditionally are associated with a poor prognosis. The management of patients with BM has become increasingly complex because of new and emerging systemic therapies and advancements in radiation oncology and neurosurgery. Current therapies include stereotactic radiosurgery, whole‐brain radiation therapy, surgical resection, laser‐interstitial thermal therapy, systemic cytotoxic chemotherapy, targeted agents, and immune‐checkpoint inhibitors. Determining the optimal treatment for a specific patient has become increasingly individualized, emphasizing the need for multidisciplinary discussions of patients with BM. Recognizing and addressing the sequelae of BMs and their treatment while maintaining quality of life and neurocognition is especially important because survival for patients with BMs has improved. The authors present current and emerging treatment options for patients with BM and suggest approaches for managing sequelae and disease recurrence.

show abstract

Section: Systemic Treatment Of Brain Metastasesmentioning

confidence: 99%

Section: Summary On Systemic Therapiesmentioning

confidence: 99%

Current multidisciplinary management of brain metastases

Moravan

Fecci

Anders

et al. 2020

Cancer

View full text Add to dashboard Cite

show abstract

“…Therefore, many trials are currently being performed to prove the efficacy of such combined therapies. It was demonstrated that patients treated with concurrent local radiotherapy and immune checkpoint inhibition had a longer OS when compared to those who received radiation either before or after starting immune checkpoint inhibition [ 131 ]. This might be a sign of an increased toxicity of combined therapies.…”

Section: Therapeutic Strategies To Overcome Immune Escape Mechanismentioning

confidence: 99%

Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma

Seliger

Massa

Yang

et al. 2020

IJMS

View full text Add to dashboard Cite

Immunotherapy has been recently approved for the treatment of relapsed and metastatic human papilloma virus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC). However, the response of patients is limited and the overall survival remains short with a low rate of long-term survivors. There exists growing evidence that complex and partially redundant immune escape mechanisms play an important role for the low efficacy of immunotherapies in this disease. These are caused by diverse complex processes characterized by (i) changes in the expression of immune modulatory molecules in tumor cells, (ii) alterations in the frequency, composition and clonal expansion of immune cell subpopulations in the tumor microenvironment and peripheral blood leading to reduced innate and adaptive immune responses, (iii) impaired homing of immune cells to the tumor site as well as (iv) the presence of immune suppressive soluble and physical factors in the tumor microenvironment. We here summarize the major immune escape strategies of HNSCC lesions, highlight pathways, and molecular targets that help to attenuate HNSCC-induced immune tolerance, affect the selection and success of immunotherapeutic approaches to overcome resistance to immunotherapy by targeting immune escape mechanisms and thus improve the HNSCC patients’ outcome.

show abstract

“…62 Improved outcomes have also been shown with metastatic lung cancer with brain metastases, whereby patients underwent stereotactic irradiation. 65 Translation of the effects of radiation therapy on response to ICI and vice versa to HNSCC patients is not yet fully understood. For example, recent research has shown that resistance to radiotherapy plus PD-L1 blockade may arise via the TIM-3 pathway and T reg activation.…”

Section: Pembrolizumab and Radiation Therapymentioning

confidence: 99%

<p>Potential of Pembrolizumab in Metastatic or Recurrent Head and Neck Cancer: Evidence to Date</p>

McCusker¹,

Orkoulas-Razis²,

Mehra³

2020

OTT

View full text Add to dashboard Cite

Relapsed and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a heterogeneous disease previously associated with poor prognosis and limited treatment options until the advent and implementation of immune checkpoint inhibitors (ICIs). The fully humanized monoclonal antibody pembrolizumab alone, or in combination with chemotherapy, was shown to have significantly improved overall survival (OS) when compared to the standard of care (SOC) EXTREME regimen consisting of the monoclonal antibody cetuximab combined with a platinum and 5-fluorouracil. Pembrolizumab with or without chemotherapy will soon supplant the EXTREME regimen that has been in use for over a decade. Given the fast-approaching significant change in the treatment algorithm for R/M HNSCC and the novelty of ICIs in general, it is important to review the literature to date to understand how this rapidly growing treatment class has come about and explore potential areas of research for the plethora of questions that remain unanswered in selecting patients appropriate for treatment with ICIs in the R/M setting. In this review, we explore the landmark trials leading to the use of ICIs for R/M HNSCC with a particular focus on pembrolizumab, the most well-studied ICI in this setting. We also provide an overview of the rationale behind the use of ICIs in relation to the immune system and challenges surrounding tumor heterogeneity and PD-L1 expression status, human papilloma virus (HPV) and the efficacy of ICI, potential of radiation therapy for enhancement of ICI response, and complications of immune-related adverse events (irAEs).

show abstract

Improved Overall Survival and Locoregional Disease Control With Concurrent PD-1 Pathway Inhibitors and Stereotactic Radiosurgery for Lung Cancer Patients With Brain Metastases

Cited by 106 publications

References 19 publications

Current multidisciplinary management of brain metastases

Current multidisciplinary management of brain metastases

Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma

<p>Potential of Pembrolizumab in Metastatic or Recurrent Head and Neck Cancer: Evidence to Date</p>

Contact Info

Product

Resources

About