Immunotherapy and Vaccination in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC).
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ABSTRACT:
SUBMITTER: Chiu LC
PROVIDER: S-EPMC8310081 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Surgical resection is the mainstay of therapy for patients with resectable and operable early stage non-small cell lung cancer (NSCLC). Surgery alone yields an unacceptably high rate of lung cancer recurrence. The addition of chemotherapy to surgery as adjuvant or neoadjuvant treatment can improve survival rates by roughly 5% at 5 years. Recently, major advances in cancer immunotherapy have led to better outcomes for many patients with lung cancer. Monoclonal antibodies to programmed death 1 and its ligand are now approved for both first and second line treatment patients with metastatic lung cancer. In this review, we will outline the rationale and current research strategies investigating the role of immunotherapy in resectable NSCLC.
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Project description:Lung cancer is the malignant tumor with the highest morbidity and mortality in the world. In recent ten years, with the emergence of new drugs and the optimization of treatment mode, the treatment of lung cancer is entering an era of precision and individualization. Neoadjuvant therapy can reduce tumor size, degrade tumor stage, kill circulating tumor cells and micrometastases in the body, afford operation possibility, and benefit the long-term survival of patients. However, the traditional neoadjuvant chemotherapy combined with surgical treatment seems to have entered the bottleneck period of efficacy and is difficult to achieve breakthrough progress. At the same time, the amazing efficacy of immunotherapy is gradually innovating the treatment mode of lung cancer. In recent years, the research data of immune checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC) shows an explosive growth. Immunotherapy has been applied to the first-line treatment of advanced NSCLC. Therefore, some clinical trials have applied immunotherapy to neoadjuvant treatment of resectable NSCLC patients. In this paper, the efficacy, possible mechanisms, potential risks and existing problems of neoadjuvant immunotherapy for resectable NSCLC patients are reviewed, and the future development direction of neoadjuvant immunotherapy is discussed.
| S-EPMC8263648 | biostudies-literature
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.
| S-EPMC8507745 | biostudies-literature
Project description:Treatment with immunotherapy has made a significant impact in the outcomes for those individuals diagnosed with metastatic non-small cell lung cancer (NSCLC) and its use is currently an established treatment modality. In light of recent advances in immunotherapy, improved survival, particularly for patients with stage IV NSCLC, has been reported with durable and prolonged responses in a subset of patients. Immune check point inhibitors, which include nivolumab, pembrolizumab, and atezolizumab, are standard treatment options in the salvage setting. Nivolumab and atezolizumab are approved for patients regardless of programmed death-ligand 1 (PD-L1) expression, whereas pembrolizumab requires tumor PD-L1 expression at the cut-off ?1%. In this review, we will outline the clinical development of immunotherapy in previously treated NSCLC, current challenges and discuss novel treatment strategies.
| S-EPMC5861264 | biostudies-literature
Project description: Not available
| S-EPMC8743523 | biostudies-literature
Project description:Surgery is the standard of care for patients with operable non-small cell lung cancer (NSCLC). However, as a single modality, surgery for early stage or locally advanced NSCLC remains associated with high rates of local and distant recurrence. The addition of neoadjuvant or adjuvant chemotherapy has modestly improved outcomes. While systemic therapy paired with surgery for other malignancies such as breast cancer have resulted in far better outcomes for equivalent stage designations, outcome improvements for operable NSCLC have lagged in part as a result of trials where adjuvant chemotherapy seemed to incur harm for stage IA patients and only modest survival benefit for stage IB-IIIA patients (AJCC 7th ed.). In recent years, immunotherapy for NSCLC has emerged as a systemic therapy with significant benefit over traditional chemotherapy regimens. These advances with immune checkpoint inhibitors (ICIs) have opened the door to administering peri-operative immunotherapy for operable NSCLC. As a result, a great multitude of studies investigating the use of immunotherapy in combination with surgery for NSCLC as well as several other malignancies have emerged. In this review, we outline the rationale for neoadjuvant immunotherapy in the treatment of operable NSCLC and summarize the available evidence that include preoperative ICI as a single modality or in combination with systemic agents and/or radiotherapy. Further, we summarize how such treatment trajectories open multiple unique windows of opportunity for scientific discovery and potential therapeutic gains for these vulnerable patients.
| S-EPMC7867741 | biostudies-literature
Project description:Locally advanced non-small cell lung cancer accounts for one third of non-small cell lung cancer (NSCLC) at the time of initial diagnosis and presents with a wide range of clinical and pathological heterogeneity. To date, the combined multimodality approach involving both local and systemic control is the gold standard for these patients, since occult distant micrometastatic disease should always be suspected. With the rapid increase in treatment options, the need for an interdisciplinary discussion involving oncologists, surgeons, radiation oncologists and radiologists has become essential. Surgery should be recommended to patients with non-bulky, discrete, or single-level N2 involvement and be included in the multimodality treatment. Resectable stage IIIA patients have been the subject of a number of clinical trials and retrospective analysis, discussing the efficiency and survival benefits on patients treated with the available therapeutic approaches. However, most of them have some limitations due to their retrospective nature, lack of exact pretreatment staging, and the involvement of heterogeneous populations leading to the awareness that each patient should undergo a tailored therapy in light of the nature of his tumor, its extension and his performance status.
| S-EPMC7465235 | biostudies-literature
Project description:BackgroundPD-L1 tumor expression has been associated with poor prognosis in a variety of solid tumors, including lung cancer, and represents a validated target for immune checkpoint inhibition in advanced malignances. It remains unknown, however, if PD-L1 can be used to predict survival in early stage, surgically treated cancers. This meta-analysis compares PD-L1 tumor expression and long term survival after surgical resection in early non-small cell lung cancer (NSCLC).MethodsPubMed was searched to identify eligible studies that compared survival of surgically resected stage I-III NSCLC patients according to PD-L1 tumor expression. Included studies were grouped according to measurement criteria of PD-L1 expression: 1%, 5%, 50% cutoffs or H-score. Meta-analysis was performed using a linear mixed-effects model to determine overall survival (OS). I2 was used as a measure of heterogeneity.ResultsThere were 40 eligible studies, including 10,380 patients. Regardless of cut-off used, higher PD-L1 tumor expression was associated with worse OS [hazard ratio (HR)1%: 1.59, 95% confidence interval (CI), 1.17-2.17; HR5%: 1.44, 95% CI, 1.03-2.00; HR50%: 1.52, 95% CI, 1.02-2.25, HRH-score: 1.34, 95% CI, 1.04-1.73]. Study heterogeneity was low and not statistically significant under all PD-L1 cutoffs.ConclusionsPD-L1 expression is consistently associated with worse survival, regardless of how it is quantified. In addition to acting as a prognostic biomarker, PD-L1 may also be used in future as a predictive biomarker for patients most likely to benefit from adjuvant immunotherapy.
| S-EPMC7481631 | biostudies-literature
Project description:PurposeImmunotherapy 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.MethodsA 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.ResultsEighteen 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.ConclusionThe 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.
| S-EPMC8628782 | biostudies-literature
Project description:The prevalence of small cell lung cancer (SCLC) has declined in the U.S. as the prevalence of tobacco use has declined. However, a significant number of people in the U.S. are current or former smokers and are at risk of developing SCLC. Routine histological or cytological evaluation can reliably make the diagnosis of SCLC, and immunohistochemistry stains (thyroid transcription factor-1, chromogranin, synaptophysin, and CD56) can be used if there is uncertainty about the diagnosis. Rarely do patients present with SCLC amendable to surgical resection, and evaluation requires a meticulous workup for extra-thoracic metastases and invasive staging of the mediastinum. Resected patients require adjuvant chemotherapy and/or thoracic radiation therapy (TRT), and prophylactic cranial radiation (PCI) should be considered depending on the stage. For limited-stage disease, concurrent platinum-etoposide and TRT followed by PCI is the standard. Thoracic radiation therapy should be started early in treatment, and can be given twice daily to 45 Gy or once daily to 60-70 Gy. For extensive-stage disease, platinum-etoposide remains the standard first-line therapy, and the standard second-line therapy is topotecan. Preliminary studies have demonstrated the activity of immunotherapy, and the response rate is approximately 10-30% with some durable responses observed. Rovalpituzumab tesirine, an antibody drug conjugate, has shown promising activity in patients with high delta-like protein 3 tumor expression (approximately 70% of patients with SCLC). The emergence of these and other promising agents has rekindled interest in drug development in SCLC. Several ongoing trials are investigating novel agents in the first-line, maintenance, and second-line settings.This review will provide an update on the standard therapies for surgically resected limited-stage small cell lung cancer and extensive-stage small cell lung cancer that have been investigated in recent clinical trials.
| S-EPMC5728020 | biostudies-literature