Special Issue "Current State of Immunotherapy for Lung Cancer"

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Thoracic Oncology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 14764

Special Issue Editor

Prof. Dr. Barbara Melosky
E-Mail Website
Guest Editor
Department of Medical Oncology, The University of British Columbia, Vancouver, BC, Canada
Interests: NSCLC; targeted therapy; EGFR; Immunotherapy

Special Issue Information

Dear Colleagues,

New therapeutic agents continue to expand the use of immunotherapy in the lung cancer setting. The recent publication of influential trials has firmly placed immunotherapy as the standard of care for wild type non-small cell lung cancer (NSCLC) in the first and second line setting in advanced disease and following chemotherapy/radiation in stage lll NSCLC. We hope it soon will be the standard of care in mesothelioma. Evidence in efficacy exists in extensive stage small cell carcinoma and this will be reviewed.  

This Special Issue is aimed at all health care providers specializing in the care of patients with lung cancer. The issue provides a thorough summary of the most recent trial results for immunotherapy in the first line setting in advanced disease including trials KEYNOTE-189 and -407 and CheckMate 227 and 9LA. As we integrate immunotherapy into our clinical practice, we need to understand how to select the patients who are most likely to benefit from this therapy. Current and emerging biomarkers will be discussed. Supporting our patients through toxicity management is another practical matter we must consider, and is relevant to all jurisdictions, not just Canada.

Despite our enthusiasm for this treatment option, immunotherapy raises other important issues that need to be discussed, including improving efficacy, decreasing cost, expanding access and evaluating how immunotherapy works in a real world situation. We encourage all contributors, especially authors from other countries, to add their voice and perspectives to the current state of immunotherapy for lung cancer.

Prof. Dr. Barbara Melosky
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Oncology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (10 papers)

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Editorial

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Editorial
Immunotherapy in Thoracic Malignancies: New Treatment and New Hope
Curr. Oncol. 2022, 29(2), 834-836; https://doi.org/10.3390/curroncol29020070 - 02 Feb 2022
Viewed by 510
Abstract
Over these last two pandemic years, we have all experienced profound changes in how we practice, how we work, and how we live [...] Full article
(This article belongs to the Special Issue Current State of Immunotherapy for Lung Cancer)

Review

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Review
Present and Emerging Biomarkers in Immunotherapy for Metastatic Non-Small Cell Lung Cancer: A Review
Curr. Oncol. 2022, 29(2), 479-489; https://doi.org/10.3390/curroncol29020043 - 21 Jan 2022
Cited by 4 | Viewed by 1636
Abstract
Targeting the immune system, especially the PDL-1/PD-1 axis, has significantly improved the outcomes of metastatic lung cancer patients. However, only a portion of patients will benefit significantly from PD(L)1 therapeutics alone or in combination with either chemotherapy or anti-CTLA4 antibody. It is therefore [...] Read more.
Targeting the immune system, especially the PDL-1/PD-1 axis, has significantly improved the outcomes of metastatic lung cancer patients. However, only a portion of patients will benefit significantly from PD(L)1 therapeutics alone or in combination with either chemotherapy or anti-CTLA4 antibody. It is therefore important to study predictive biomarkers to help select the patients who will experience the most benefit from immunotherapy. In this paper, the current status of PDL-1 expression on tumour cells, the smoking status of patients, tumour mutational burden, gut microbiome and STK11 and KEAP1 mutations in the tumour as predictive biomarkers for PD(L)-1-based immunotherapy are summarized. Full article
(This article belongs to the Special Issue Current State of Immunotherapy for Lung Cancer)
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Review
New Strategies and Combinations to Improve Outcomes in Immunotherapy in Metastatic Non-Small-Cell Lung Cancer
Curr. Oncol. 2022, 29(1), 38-55; https://doi.org/10.3390/curroncol29010004 - 23 Dec 2021
Cited by 4 | Viewed by 1573
Abstract
Immune checkpoint inhibitors have transformed the treatment of metastatic non-small-cell lung cancer, yielding marked improvements in survival and the potential for durable clinical responses. Primary and acquired resistance to current immune checkpoint inhibitors constitute a key challenge despite the remarkable responses observed in [...] Read more.
Immune checkpoint inhibitors have transformed the treatment of metastatic non-small-cell lung cancer, yielding marked improvements in survival and the potential for durable clinical responses. Primary and acquired resistance to current immune checkpoint inhibitors constitute a key challenge despite the remarkable responses observed in a subset of patients. Multiple novel combination immunotherapy and adoptive cell therapy strategies are presently being developed to address treatment resistance. The success of these strategies hinges upon rational clinical trial design as well as careful consideration of the immunologic mechanisms within the variable tumor immune microenvironment (TIME) which underpin resistance to immunotherapy. Further research is needed to facilitate a deeper understanding of these complex mechanisms within the TIME, which may ultimately provide the key to restoring and enhancing an effective anti-tumor immune response. This review aims to provide an introduction to some of the recent and notable combination immunotherapy and cell therapy strategies used in advanced non-small-cell lung cancer (NSCLC), and the rationale for their use based on current understanding of the anti-tumor immune response and mechanisms of resistance within the TIME. Full article
(This article belongs to the Special Issue Current State of Immunotherapy for Lung Cancer)
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Review
The Evolving Role of Immunotherapy in Stage III Non-Small Cell Lung Cancer
Curr. Oncol. 2021, 28(6), 5408-5421; https://doi.org/10.3390/curroncol28060451 - 16 Dec 2021
Cited by 1 | Viewed by 1276
Abstract
The management of Stage III non-small cell lung cancer (NSCLC) is complex and requires multidisciplinary input. Since the publication of the PACIFIC trial (consolidative durvalumab post concurrent chemotherapy and radiation in Stage III disease) which showed improved survival for patients in the immunotherapy [...] Read more.
The management of Stage III non-small cell lung cancer (NSCLC) is complex and requires multidisciplinary input. Since the publication of the PACIFIC trial (consolidative durvalumab post concurrent chemotherapy and radiation in Stage III disease) which showed improved survival for patients in the immunotherapy arm, there has been much interest in the use of immunotherapy in the Stage III setting. In this review, we explore the biologic and clinical rationale for the use of immunotherapy in Stage III NSCLC, present previously published and upcoming data in the neoadjuvant, adjuvant, and concurrent realms of Stage III management, and discuss unanswered questions and challenges moving forward. Full article
(This article belongs to the Special Issue Current State of Immunotherapy for Lung Cancer)
Review
The Challenge to the Pathologist of PD-L1 Expression in Tumor Cells of Non-Small-Cell Lung Cancer—An Overview
Curr. Oncol. 2021, 28(6), 5227-5239; https://doi.org/10.3390/curroncol28060437 - 08 Dec 2021
Cited by 2 | Viewed by 1205
Abstract
In recent years, the treatment of non-small-cell lung cancer (NSCLC) has been fundamentally changed by immunotherapy where the immune system is reactivated using anti-programmed cell death protein 1/programmed death ligand 1 (PD1/PD-L1) checkpoint inhibition. With this, the immunohistological detection of PD-L1 has become [...] Read more.
In recent years, the treatment of non-small-cell lung cancer (NSCLC) has been fundamentally changed by immunotherapy where the immune system is reactivated using anti-programmed cell death protein 1/programmed death ligand 1 (PD1/PD-L1) checkpoint inhibition. With this, the immunohistological detection of PD-L1 has become one of the most important predictive biomarkers, leading pathologists to play a central role in the immuno-oncological therapy decisions. This has brought them the challenge of requiring the knowledge of relevant checkpoint inhibitors (CI), different PD-L1 scores and cut-offs as well as the choice of the right tissues and controls. Their involvement is also required in the careful validation of both clinical trial assays (CTAs) and laboratory developed tests (LDTs), in addition to the internal and external quality assessment and the interpretation and scoring of the staining based on specialist training. After the training of tumor proportion score (TPS) scoring in NSCLC, pathologists show a high level of concordance, with some variation between different cut-offs. Since not all patients benefit from immunotherapy, further research is needed to validate new predictive markers and optimize existing ones. In this context, these studies focus on a combination of PD-L1 and molecular signatures. Full article
(This article belongs to the Special Issue Current State of Immunotherapy for Lung Cancer)
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Review
The Role of Immunotherapy in the Treatment of Malignant Pleural Mesothelioma
Curr. Oncol. 2021, 28(6), 4542-4551; https://doi.org/10.3390/curroncol28060385 - 08 Nov 2021
Cited by 2 | Viewed by 1021
Abstract
Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient [...] Read more.
Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos. With an improved understanding of the relationship between the immune system and cancer progression, immunotherapies are playing a greater role in the treatment of many cancers. Several early- and late-phase trials in malignant pleural mesothelioma, including assessments of the first-line efficacy of combination ipilimumab/nivolumab treatment, have now demonstrated promising results for both immune checkpoint inhibition and cell-based therapies. These immune therapies are likely to play a central role in the treatment of this disease going forward. Full article
(This article belongs to the Special Issue Current State of Immunotherapy for Lung Cancer)
Review
Immunotherapy in the First-Line Setting in Wild-Type NSCLC
Curr. Oncol. 2021, 28(6), 4457-4470; https://doi.org/10.3390/curroncol28060378 - 03 Nov 2021
Cited by 4 | Viewed by 1569
Abstract
Treatment algorithms in the treatment of advanced non-small cell lung cancer (NSCLC) continue to evolve as new therapeutics show positive efficacy improvements. This review article summarizes the data for the use of immunotherapy for treatment in first-line stage IV NSCLC, organized by the [...] Read more.
Treatment algorithms in the treatment of advanced non-small cell lung cancer (NSCLC) continue to evolve as new therapeutics show positive efficacy improvements. This review article summarizes the data for the use of immunotherapy for treatment in first-line stage IV NSCLC, organized by the following four sections: single-agent immunotherapy, immunotherapy and chemotherapy, dual immunotherapy, and dual immunotherapy and chemotherapy. The results are summarized and tabulated. Finally, application of the trial data is illustrated in four clinical scenarios depending on the programmed death-ligand 1 (PD-L1) expression levels. Single checkpoint inhibitors have become an easy and excellent treatment in patients whose tumors have high PD-L1 expression. Adding chemotherapy to immunotherapy benefits our patients. Immunotherapy, with or without chemotherapy, is now the standard of care in the first-line setting in patients without EGFR, ALK, or ROS driver mutations. Full article
(This article belongs to the Special Issue Current State of Immunotherapy for Lung Cancer)
Review
The Price of Success: Immune-Related Adverse Events from Immunotherapy in Lung Cancer
Curr. Oncol. 2021, 28(6), 4392-4407; https://doi.org/10.3390/curroncol28060373 - 02 Nov 2021
Cited by 3 | Viewed by 1081
Abstract
Cancer immunotherapy has the goal of enhancing a patient’s intrinsic immune processes in order to mount a successful immune response against tumor cells. Cancer cells actively employ tactics to evade, delay, alter, or attenuate the anti-tumor immune response. Immune checkpoint inhibitors (ICIs) modulate [...] Read more.
Cancer immunotherapy has the goal of enhancing a patient’s intrinsic immune processes in order to mount a successful immune response against tumor cells. Cancer cells actively employ tactics to evade, delay, alter, or attenuate the anti-tumor immune response. Immune checkpoint inhibitors (ICIs) modulate endogenous regulatory immune mechanisms to enhance immune system activation, and have become the mainstay of therapy in many cancer types. This activation occurs broadly and as a result, activation is supraphysiologic and relatively non-specific, which can lead to immune-related adverse events (irAEs), the frequency of which depends on the patient, the cancer type, and the specific ICI antibody. Careful assessment of patients for irAEs through history taking, physical exam, and routine laboratory assessments are key to identifying irAEs at early stages, when they can potentially be managed more easily and before progressing to higher grades or more serious effects. Generally, most patients with low grade irAEs are eligible for re-challenge with ICIs, and the use of corticosteroids to address an irAE is not associated with poorer patient outcomes. This paper reviews immune checkpoint inhibitors (ICIs) including their mechanisms of action, usage, associated irAEs, and their management. Full article
(This article belongs to the Special Issue Current State of Immunotherapy for Lung Cancer)
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Review
Immunotherapy in Extensive-Stage Small Cell Lung Cancer
Curr. Oncol. 2021, 28(5), 4093-4108; https://doi.org/10.3390/curroncol28050347 - 12 Oct 2021
Cited by 8 | Viewed by 2008
Abstract
Small cell lung cancer (SCLC) remains a poorly understood disease with aggressive features, high relapse rates, and significant morbidity as well as mortality, yet persistently limited treatment options. For three decades, the treatment algorithm of SCLC has been stagnant despite multiple attempts to [...] Read more.
Small cell lung cancer (SCLC) remains a poorly understood disease with aggressive features, high relapse rates, and significant morbidity as well as mortality, yet persistently limited treatment options. For three decades, the treatment algorithm of SCLC has been stagnant despite multiple attempts to find alternative therapeutic options that could improve responses and increase survival rates. On the other hand, immunotherapy has been a thriving concept that revolutionized treatment options in multiple malignancies, rendering previously untreatable diseases potentially curable. In extensive stage SCLC, immunotherapy significantly altered the course of disease and is now part of the treatment algorithm in the first-line setting. Nevertheless, the important questions that arise are how best to implement immunotherapy, who would benefit the most, and finally, how to enhance responses. Full article
(This article belongs to the Special Issue Current State of Immunotherapy for Lung Cancer)
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Other

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Systematic Review
Meta-Analysis of Neoadjuvant Immunotherapy for Patients with Resectable Non-Small Cell Lung Cancer
Curr. Oncol. 2021, 28(6), 4686-4701; https://doi.org/10.3390/curroncol28060395 - 14 Nov 2021
Cited by 8 | Viewed by 1720
Abstract
Purpose: Immunotherapy has created a paradigm shift in the treatment of metastatic non-small cell lung cancer (NSCLC), overcoming the therapeutic plateau previously achieved by systemic chemotherapy. There is growing interest in the utility of immunotherapy for patients with resectable NSCLC in the neoadjuvant [...] Read more.
Purpose: Immunotherapy has created a paradigm shift in the treatment of metastatic non-small cell lung cancer (NSCLC), overcoming the therapeutic plateau previously achieved by systemic chemotherapy. There is growing interest in the utility of immunotherapy for patients with resectable NSCLC in the neoadjuvant setting. The present systematic review and meta-analysis aim to provide an overview of the existing evidence, with a focus on pathological and radiological response, perioperative clinical outcomes, and long-term survival. Methods: A systematic review was conducted using electronic databases from their dates of inception to August 2021. Pooled data on pathological response, radiological response, and perioperative outcomes were meta-analyzed where possible. Results: Eighteen publications from sixteen studies were identified, involving 548 enrolled patients who underwent neoadjuvant immunotherapy, of whom 507 underwent surgery. Pathologically, 52% achieved a major pathological response, 24% a complete pathological response, and 20% reported a complete pathological response of both the primary lesion as well as the sampled lymph nodes. Radiologically, 84% of patients had stable disease or partial response. Mortality within 30 days was 0.6%, and morbidities were reported according to grade and frequency. Conclusion: The present meta-analysis demonstrated that neoadjuvant immunotherapy was feasible and safe based on perioperative clinical data and completion rates of surgery within their intended timeframe. The pathological response after neoadjuvant immunotherapy was superior to historical data for patients who were treated with neoadjuvant chemotherapy alone, whilst surgical and treatment-related adverse events were comparable. The limitations of the study included the heterogenous treatment regimens, lack of long-term follow-up, variations in the reporting of potential prognostic factors, and potential publication bias. Full article
(This article belongs to the Special Issue Current State of Immunotherapy for Lung Cancer)
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