The Evolving Role of Immunotherapy in Stage III Non-Small Cell Lung Cancer.
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ABSTRACT:
SUBMITTER: Perdrizet K
PROVIDER: S-EPMC8700596 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Simple Summary The treatment of resectable stage III non-small-cell lung cancer with N2 lymph node involvement is usually multimodal and is generally based on neoadjuvant chemotherapy +/− radiotherapy followed by surgery, but the cure rate is still low. Immunotherapy based on anti-PD1/PD-L1 immune checkpoint inhibitors has improved survival in advanced and stage III non-resectable NSCLC patients and is being studied in earlier stages to improve the cure rate of lung cancer. In this article, we review all therapeutic approaches to stage III-N2 NSCLC, analysing both completed and ongoing studies that evaluate the addition of immunotherapy with or without chemotherapy and/or radiotherapy. Abstract Stage III non-small-cell lung cancer (NSCLC) with N2 lymph node involvement is a heterogeneous group with different potential therapeutic approaches. Patients with potentially resectable III-N2 NSCLC are those who are considered to be able to receive a multimodality treatment that includes tumour resection after neoadjuvant therapy. Current treatment for these patients is based on neoadjuvant chemotherapy +/− radiotherapy followed by surgery and subsequent assessment for adjuvant chemotherapy and/or radiotherapy. In addition, some selected III-N2 patients could receive upfront surgery or pathologic N2 incidental involvement can be found a posteriori during analysis of the surgical specimen. The standard treatment for these patients is adjuvant chemotherapy and evaluation for complementary radiotherapy. Despite being a locally advanced stage, the cure rate for these patients continues to be low, with a broad improvement margin. The most immediate hope for improving survival data and curing these patients relies on integrating immunotherapy into perioperative treatment. Immunotherapy based on anti-PD1/PD-L1 immune checkpoint inhibitors is already a standard treatment in stage III unresectable and advanced NSCLC. Data from the first phase II studies in monotherapy neoadjuvant therapy and, in particular, in combination with chemotherapy, are highly promising, with impressive improved and complete pathological response rates. Despite the lack of confirmatory data from phase III trials and long-term survival data, and in spite of various unresolved questions, immunotherapy will soon be incorporated into the armamentarium for treating stage III-N2 NSCLC. In this article, we review all therapeutic approaches to stage III-N2 NSCLC, analysing both completed and ongoing studies that evaluate the addition of immunotherapy with or without chemotherapy and/or radiotherapy.
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Project description:Until recently, the standard treatment in unresectable stage III non-small cell lung cancer was concurrent chemoradiotherapy, but often with dismal outcome. The introduction of consolidation treatment with immune checkpoint inhibitors has shifted the treatment landscape and prognosis of these patients. However, patients whose tumors harbors an epidermal growth factor receptor (EGFR) mutation derived less benefit, with an increased risk of immune-related adverse events. Moreover, current data suggested that patients with oncogenic addicted tumors, mainly EGFR-positive tumors, and also anaplastic lymphoma kinase (ALK)-positive have poorer progression free survival after chemoradiotherapy. Indeed, these tumors have also inferior distant control compared with those who have wild-type disease, especially in the central nervous system, highlighting the need for assessing the role of targeted therapies in this patient population. It is speculated that outcome could probably increase with a consolidation treatment strategy including an EGFR tyrosine kinase inhibitor. However, a personalized treatment approach is not considered standard of care in this setting due to lack of robust evidence, as the majority of trials were performed in unselected patients, number of patients is limited and the majority of these studies were underpowered. In this review we summarize the role of tyrosine kinase inhibitors in unresectable stage III NSCLC, specifically focusing on EGFR-mutant tumors.
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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.
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Project description:Background:The management of unresectable stage iii non-small-cell lung cancer (nsclc) is complex and best determined through multidisciplinary consultation. A longitudinal, population-level study was carried out to describe the management approach and outcomes of treatment in the real-world setting in Ontario. Methods:Individuals diagnosed with nsclc between 1 April 2010 and 31 March 2015 were identified in the Ontario Cancer Registry. Unresectable disease was defined as no surgery reported within 3 months of diagnosis. Initial treatments included radiotherapy (rt, curative or palliative), chemotherapy, targeted therapy, and chemoradiation [crt, concurrent (ccrt) or sequential (scrt)]. Survival was calculated from diagnosis with stage iii disease to death or last follow-up. Results:Of the 24,729 individuals diagnosed with nsclc, 5243 (21.2%) had stage iii disease, with most of the latter group (4542, 86.6%) having unresectable disease. Median age was 70 years, and 54.2% were men. The frequency of first-line treatment was ccrt, 22.1%; palliative rt, 21.0%; curative rt, 19.6%; no treatment, 19.6%; chemotherapy alone, 11.6%; scrt, 5.4%; and targeted therapy, 0.7%. Median overall survival (mos) was 14.2 months [95% confidence interval (ci): 13.6 months to 14.7 months], with the longest survival observed in patients who received targeted therapy (mos: 34.7 months; 95% ci: 21.4 months to 51.2 months), and the poorest, in those receiving no cancer treatment (mos: 5.9 months; 95% ci: 5.0 months to 6.4 months). The mos in patients receiving ccrt was 23.6 months (95% ci: 21.4 months to 25.6 months). Conclusions:Guideline-recommended ccrt is undertaken in only a small proportion of patients with unresectable nsclc in Ontario. The reasons for low uptake of that recommendation are only partly understood.
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