Project description:Targeted therapy and immunotherapy have changed the treatment modes for advanced non-small cell lung cancer (NSCLC), moving from second-line to first-line treatment and significantly extending patients' survival. Surgery and chemoradiotherapy remain the main treatment options for patients with locally advanced lung cancer, but recurrence and metastasis still occur in some patients. The survival rates of conventional perioperative chemotherapy among NSCLC patients have increased by only 5%. Therefore, more studies have begun to explore targeted and immune neoadjuvant/adjuvant therapies in early-stage and locally advanced NSCLC, and the relevant clinical research data have shown good efficacy and safety profiles. This article summarizes several clinical studies of critical importance.
Project description:Lung cancer (LC) is associated with ageing, with the average age of affected individuals being approximately 70 years. However, despite a higher incidence and prevalence among older people, the older adult population is underrepresented in clinical trials. For LC with Epidermal Growth Factor Receptor (EGFR) mutations, there is no clear association of this mutation with age. Geriatric assessments (GAs) and a multidisciplinary approach are essential for defining the optimal treatment. In this consensus, a group of experts selected from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sección de Oncogeriatría de la Sociedad Española de Oncología Médica-SEOM), the Spanish Lung Cancer Group (Grupo Español de Cáncer de Pulmón-GECP) and the Association for Research on Lung Cancer in Women (Asociación para la Investigación del Cáncer de Pulmón en Mujeres-ICAPEM) evaluate the scientific evidence currently available and propose a series of recommendations to optimize the management of older adult patients with advanced LC with EGFR mutations.
Project description:Lung cancer is one of the leading causes of cancer-related death. Lung cancer mortality has decreased over the past decade, which is partly attributed to improved treatments. Curative surgery for patients with early-stage lung cancer is the standard of care, but not all surgical treatments have a good prognosis. Adjuvant and neoadjuvant chemotherapy are used to improve the prognosis of patients with resectable lung cancer. Immunotherapy, an epoch-defining treatment, has improved curative effects, prognosis, and tolerability compared with traditional and ordinary cytotoxic chemotherapy, providing new hope for patients with non-small cell lung cancer (NSCLC). Immunotherapy-related clinical trials have reported encouraging clinical outcomes in their exploration of different types of perioperative immunotherapy, from neoadjuvant immune checkpoint inhibitor (ICI) monotherapy, neoadjuvant immune-combination therapy (chemoimmunotherapy, immunotherapy plus antiangiogenic therapy, immunotherapy plus radiotherapy, or concurrent chemoradiotherapy), adjuvant immunotherapy, and neoadjuvant combined adjuvant immunotherapy. Phase 3 studies such as IMpower 010 and CheckMate 816 reported survival benefits of perioperative immunotherapy for operable patients. This review summarizes up-to-date clinical studies and analyzes the efficiency and feasibility of different neoadjuvant therapies and biomarkers to identify optimal types of perioperative immunotherapy for NSCLC.
Project description:Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) comprises approximately 85% of lung cancers and, unfortunately, more than half of these patients are diagnosed with metastatic disease. Platinum-based chemotherapy has for long been the standard frontline therapy for advanced disease. Despite remarkable advances in targeted therapy for a subset of patients harboring a driver mutation, the prognosis in the majority of the lung cancer population have not changed significantly. More recently, immunotherapy has drastically changed the treatment of NSCLC and have established a new treatment paradigm for these patients. Pembrolizumab is now the new mainstay first-line treatment for those with high-PD-L1 expression. However, many questions remain regarding how to sequence and combine these agents in the frontline setting. The optimal patient selection strategies are also unclear. High PD-L1 expression is associated with higher response rates, but even patients with low or absent PD-L1 expression benefit from these drugs. More recently, tumor mutational burden is been proposed as a potential predictive marker for response. This article will review the data regarding the usage of immunotherapy in treatment naive advanced NSCLC.
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.?.
Project description:Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib) or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib). As a result, anti-PD-1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs. Here, we discuss advances in immunotherapy for the treatment of metastatic non-small-cell lung cancer as well as future perspectives within this framework.
Project description:Currently, the predictive role of POLE mutations for immunotherapy is under intense investigation. The POLE gene encodes one of the four subunits of DNA polymerase important for DNA replication and repair. POLE mutations are related to other favorable predicative factors such as high expression of PD-L1, high TMB, and infiltration of CD8+ cells in the tumor microenvironment. No formal clinical trials studied the efficacy of immunotherapy in lung patients harboring POLE mutation, and only few cases were mentioned in the literature. Moreover, lung cancer patients are prone to brain metastasis, which is notorious for the unresponsiveness to chemotherapy. The efficacy of immunotherapy for brain metastasis is still controversial. Here, we described a case of a POLEmt non-small-cell lung cancer (NSCLC) patient with brain metastasis who was treated with immunotherapy. His brain lesions disappeared after treatment. Our report strongly supported the benefit of immune-combined therapy for advanced NSCLC patients with POLE mutation, even with brain metastasis.
Project description:Currently, immunotherapy is widely used in the treatment of various stages of non-small cell lung cancer. According to clinical experience and results of previous studies, immunotherapy as neoadjuvant therapy seems to exhibit better efficacy against early resectable non-small cell lung cancer as compared to advanced lung cancer, which is often defined as unresectable non-small cell lung cancer. However, this observation has not been established in clinical studies. This systematic review aimed to evaluate the efficacy of immunotherapy in early and late lung cancer, wherein objective response rate (ORR) and disease control rate (DCR) were used as evaluation indexes. The present study also evaluated the safety of immunotherapy in early and late lung cancer, wherein the rate of treatment-related adverse reactions (TRAEs) was used as an indicator. Electronica databases, including PubMed, Cochrane Library, Embase, and other databases, were searched to identify relevant studies. Besides this, all the available reviews, abstracts, and meeting reports from the main international lung cancer meetings were searched manually. ORR, DCR, and TRAEs were extracted as the primary outcomes. A total of 52 randomized controlled trials involving 13,660 patients were shortlisted. It was observed that immunotherapy alone significantly improved DCR in early lung cancer in comparison to advanced lung cancer. Importantly, the improvement in ORR was not to the same extent as reported in the case of advanced lung cancer. The combination of immunotherapy with other therapies, especially immunochemotherapy, significantly improved ORR and DCR in early lung cancer. In terms of safety, immunotherapy either alone or in combination with other therapies exhibited a better safety profile in early lung cancer than in advanced lung cancer. Altogether, the benefits of immunotherapy in early lung cancer appeared to be better than those observed in advanced lung cancer, especially with the regard to the regimen of immunotherapy in combination with chemotherapy. In terms of safety, both immunotherapy alone and its combination with chemotherapy were found to be safer in early lung cancer as compared to advanced lung cancer.