Combination strategies of immunotherapy in non-small cell lung cancer: facts and challenges.
Ontology highlight
ABSTRACT: Abstract
Immunotherapy has dramatically altered the treatment of non-small cell lung cancer. Currently, the emergence of combination strategies in immunotherapy has brightened the prospects of improved clinical outcomes and manageable safety profiles in the first/second-line settings. However, sub-optimal response rates are still observed in several clinical trials. Hence, alternative combination models and candidate selection strategies need to be explored. Herein, we have critically reviewed and commented on the published data from several clinical trials, including combined immunotherapy and chemotherapy, anti-angiogenic agents, epidermal growth factor receptor/anaplastic lymphoma kinase tyrosine kinase inhibitors, radiotherapy, and other immune checkpoint inhibitors.
SUBMITTER: Li CL
PROVIDER: S-EPMC8382384 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Immune checkpoint inhibitors enhance the activation and antitumor activity of the immune system, resulting in durable response rates in a select group of patients. Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1) and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of T-cell effector function. These therapeutic drugs were originally evaluated in patients with metastatic melanoma before expansion to all tumor types, including non-small cell lung cancer (NSCLC) with promising results. The PD1 inhibitors such as pembrolizumab have now received FDA approval in the first-line setting for patients with positive PD-L1 expression tumor types; however, only a portion of patients have shown objective and sustainable responses. To expand the number of patients with observed response to immunotherapeutic agents including patients with negative PD-L1 expression tumors, clinical trials are ongoing to assess the safety and efficacy of combination immune checkpoint inhibitors and combination immune checkpoint inhibitors with targeted therapy. Immune checkpoint inhibitors have been found to be a promising therapeutic drug class with sustainable response rates and a tolerable safety profile, and efforts continue to improve these drugs in patients with NSCLC.
| S-EPMC5861267 | biostudies-literature
Project description:Immune-checkpoint inhibitors (ICI), particularly inhibitors of the PD-1 axis, have altered the management of non-small cell lung cancer (NSCLC) over the last 10 years. First demonstrated to improve outcomes in second-line or later therapy of advanced disease, ICIs were shown to improve overall survival compared with chemotherapy in first-line therapy for patients whose tumors express PD-L1 on at least 50% of cells. More recently, combining ICIs with chemotherapy has been shown to improve survival in patients with both squamous and nonsquamous NSCLC, regardless of PD-L1 expression. However, PD-L1 and, more recently, tumor mutational burden have not proven to be straightforward indicative biomarkers. We describe the advances to date in utilizing these biomarkers, as well as novel markers of tumor inflammation, to ascertain which patients are most likely to benefit from ICIs. Ongoing translational work promises to improve the proportion of patients who benefit from these agents.
| S-EPMC6679805 | biostudies-literature
Project description:Immunotherapy has represented one of the main medical revolutions of recent decades, and is currently a consolidated treatment for different types of tumors at different stages and scenarios, and is present in a multitude of clinical trials. One of the diseases in which it is most developed is non-small cell lung cancer. The combination of radiotherapy and immunotherapy in cancer in general and lung cancer in particular currently represents one of the main focuses of basic and clinical research in oncology, due to the synergy of this interaction, which can improve tumor response, resulting in improved survival and disease control. In this review we present the biochemical and molecular basis of the interaction between radiotherapy and immunotherapy. We also present the current clinical status of this interaction in each of the stages and cases of non-small cell lung cancer, with the main results obtained in the different studies both in terms of tumor response and survival as well as toxicity. Finally, we mention the main studies underway and the challenges of this interaction in the coming years, including how these treatments should be combined to achieve the greatest efficacy with the fewest possible side effects (dose, type of radiotherapy and drugs, sequence of treatments).
| S-EPMC8641011 | biostudies-literature
Project description: Not available
| S-EPMC8143766 | biostudies-literature
Project description:Treatment for the most common form of cancer (lung cancer) has historically involved use of cytotoxic chemotherapy. With the advent of mutation analysis, more therapies beyond traditional cytotoxics have been discovered. Most recently, the use of immunotherapy has entered the treatment arsenal of non-small cell lung cancer (NSCLC). This review aims to summarize the current and future use of immunotherapy in the treatment of NSCLC.
| S-EPMC4630527 | biostudies-literature
Project description:Programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitor has become one of the important treatment options for patients with advanced non-small cell lung cancer (NSCLC). However, only a small subset of patients with NSCLC can currently receive single-agent PD-1 inhibitors as first-line therapy, for the limitations of population selection exclude most patients from immuno-oncology (IO) monotherapy. In order to expand the candidate population for IO first-line treatment and make more newly diagnosed patients benefit from IO treatment, a series of studies are focusing on the combination of IO and other drugs in NSCLC. We reviewed the latest clinical data of IO first-line combination therapy in recent years, suggesting that on the basis of PD-1/PD-L1 inhibitors, combined with other IO, chemotherapy, anti-angiogenic drugs, targeted therapy or radiotherapy may produce synergistic anti-tumor effects. It is expected to benefit more newly diagnosed patients.?.
| S-EPMC6318566 | biostudies-literature
Project description:Immunotherapy has become an increasingly important therapeutic strategy for those with cancer, with phase III studies demonstrating survival advantages in melanoma and castration-resistant prostate cancer. Non-small cell lung cancer (NSCLC) is a promising target for the next generation of immune-based strategies. In this article, we examine the current state of the art in lung cancer immunotherapy, including vaccines that specifically target lung tumor antigens and immune checkpoint antibodies such as antiprogrammed death 1 (anti-PD-1). Both approaches harness innate immunity against tumors by suppressing tumor-induced immune paresis. Methods. To identify relevant clinical trials of immunotherapy in NSCLC, PubMed and Medline databases were searched using the terms "immunotherapy" and "NSCLC," and several other therapy-specific search terms (e.g., PD-1, NSCLC). Additionally, abstracts presented at international lung cancer symposia, the American Society of Clinical Oncology annual meeting, and the European Society of Medical Oncology annual meeting between 2005 and 2013 were evaluated. Results. Large international phase III trials of NSCLC vaccines have completed accrual in both the adjuvant and metastatic disease settings. Results of the START study were disappointing, but results from other studies are still awaited. Immune checkpoint modulation has shown promise, with separate phase I studies of the anti-PD-1 antibody, nivolumab, and anti-PD-L1 antibody, MPDL3280A, demonstrating good tolerance and durable responses for certain patients with NSCLC who were heavily pretreated. Conclusions. Immune-based strategies have shown initial promise for early- and advanced-stage NSCLC. Validating these findings in randomized studies and discovering durable biomarkers of response represent the next challenges for investigation.
| S-EPMC3825306 | biostudies-other
Project description:Simple Summary Non-small cell lung cancer is the most common type of lung cancer. Anaplastic Lymphoma Kinase (ALK) rearrangements have been found in 5–6% of non-small cell lung cancers. While ALK rearranged non-small cell lung cancer is exquisitely sensitive to ALK directed targeted therapies, it is generally resistant to immune-based therapies. We aim to describe the mechanisms by which ALK-rearranged non-small cell lung cancers escape host immunity and are thereby unresponsive to immunotherapies. Furthermore, we describe new immunotherapy strategies and the promises and challenges in incorporating these into clinical practice. Abstract Rearrangements in the Anaplastic Lymphoma Kinase (ALK) gene have been implicated in 5–6% of all non-small cell lung cancers. ALK-rearranged non-small cell lung cancers are sensitive to ALK-directed tyrosine kinase inhibitors, but generally resistant to single-agent immune checkpoint inhibitors. Here, we aim to describe the mechanisms of ALK aberrations in non-small cell lung cancer by which an immunosuppressed tumor microenvironment is created, leading to host immune evasion. We report pre-clinical and clinical studies evaluating novel immunotherapeutic approaches and describe the promises and challenges of incorporating immune-based treatments for ALK-rearranged non-small cell lung cancer.
| S-EPMC8004790 | biostudies-literature
Project description:Small cell lung cancer (SCLC) is a highly lethal disease, characterized by early metastasis and rapid growth, and no effective treatment after relapse. Etoposide-platinum (EP) combination has been the backbone therapy of SCLC over the past 30 years. It is extremely urgent and important to seek new therapies for SCLC. In the past 5 years, immunotherapy, such as immune checkpoint inhibitors programmed cell death protein-1 (PD-1), cytotoxic T lymphocyte associatedprotein-4 (CTLA-4), has made remarkable achievements in the treatment of patients with SCLC, and it has become the first-line option for the treatment of some patients. Some traditional chemotherapeutic drugs or targeted drugs, such as alkylating agent temozolomide and transcription inhibitor lurbinectedin, have been found to have immunomodulatory effects and are expected to become new immunotherapeutic agents. In this study, we aimed to review the efficacy of new treatments for SCLC and discuss the current challenges and application prospect in the treatment of SCLC patients.
| S-EPMC7072020 | biostudies-literature
Project description:Treatment for advanced non-small cell lung cancer (NSCLC) has been significantly improved in recent years with the incorporation of drugs targeting antiangiogenesis and more specifically genomic alterations such as the EGFR mutations and ALK translocations. However, most patients invariably progress and die. The emergence of immune checkpoint inhibitors targeting the pathways involved in tumor-induced immunosuppression have redefined the management of the disease, achieving significant long-lasting responses with manageable safety profiles, regardless of histology. Still, response rates with immunotherapy are deemed suboptimal. Current efforts are focusing on new potential combination strategies with synergistic antitumor activity, using immune checkpoint blockade as a partner for targeted agents. Herein we discuss the available data on the combined use of immunotherapy, including PD-1/PD-L1 and CTLA-4 inhibitors, with EGFR and ALK inhibitors and comment on the current status of immunotherapy plus antiangiogenic drugs for molecularly unselected advanced NSCLC.
| S-EPMC5784559 | biostudies-literature