The beginning of the perioperative immunotherapy era in early-stage non-small cell lung cancer.
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ABSTRACT:
SUBMITTER: Riano I
PROVIDER: S-EPMC10713273 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
Publications
The beginning of the perioperative immunotherapy era in early-stage non-small cell lung cancer.
Riano Ivy I Dragnev Konstantin H KH Phillips Joseph D JD
Translational lung cancer research 20231101 11
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Project description:Surgery or concurrent chemoradiation are standard of care treatments for patients with localized and locally advanced non-small cell lung cancer (NSCLC). While resection and chemoradiation are potentially curative therapies for early-stage disease, relapse rates remain high. Adjuvant or neoadjuvant chemotherapy improves cure rates 5-15% compared with surgery alone for patients with resectable disease. Immune checkpoint inhibitors (ICI) have heralded a new era for the treatment of advanced NSCLC with one-third of patients experiencing long-term survival. There is increasing interest in examining the role of ICI therapy in patients with early-stage NSCLC. Consolidation durvalumab after chemoradiation has become a part of standard of care for patients with inoperable, locally advanced disease. More recently, there is emerging evidence that neoadjuvant treatment with ICIs results in substantial rates of major pathologic response and pathologic complete response, and high rates of R0 resection with no significant delay in time to surgery. Furthermore, preliminary data show that adjuvant treatment with ICIs after adjuvant chemotherapy improves disease-free survival and may play a critical role in reducing disease recurrence in patients with resectable disease. In this review, we discuss recently reported and ongoing studies that are designed to define the role of immunotherapy in patients with non-metastatic NSCLC.
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Project description:Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, only 0.8%-2.5% of the patients presented complete response after chemoimmunotherapy. Considering that ES-SCLC is highly sensitive to radiotherapy, the addition of radiotherapy after first-line treatment for ES-SCLC could further improve local control, which may be beneficial for patients' survival. Prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy. However, the efficacy and safety of cTRT in the immunotherapy era remain unclear owing to a lack of prospective studies. Prophylactic cranial irradiation (PCI) has been shown to decrease brain metastasis (BM) and prolong survival in patients with limited-stage SCLC in previous reports. However, according to current guidelines, PCI is not commonly recommended for ES-SCLC. Immunotherapy has the potential to reduce the incidence of BM. Whether PCI can be replaced with regular magnetic resonance imaging surveillance for ES-SCLC in the era of immunotherapy remains controversial. Whole brain radiation therapy (WBRT) is the standard treatment for BM in SCLC patients. Stereotactic radiosurgery (SRS) has shown promise in the treatment of limited BM. Considering the potential of immunotherapy to decrease BM, it is controversial whether SRS can replace WBRT for limited BM in the immunotherapy era. Additionally, with the addition of immunotherapy, the role of palliative radiotherapy may be weakened in patients with asymptomatic metastatic lesions. However, it is still indispensable and urgent for patients with obvious symptoms of metastatic disease, such as spinal cord compression, superior vena cava syndrome, lobar obstruction, and weight-bearing metastases, which may critically damage the quality of life and prognosis. To improve the outcome of ES-SCLC, we discuss the feasibility of radiotherapy, including cTRT, PCI, WBRT/SRS, and palliative radiotherapy with immunotherapy based on existing evidence, which may offer specific prospects for further randomized trials and clinical applications.
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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.
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Project description:Currently, chemotherapy is the standard adjuvant treatment for early-stage non-small cell lung cancer (NSCLC). However, adjuvant cisplatin-based chemotherapy after surgery has been shown to improve 5-year survival rates by only 4-5%. Immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced NSCLC, there is a growing interest in the role of immunotherapy in early-stage NSCLC. Here, we summarize the rationale for adjuvant immunotherapy, including the postoperative immunosuppressive environment and immunological effects of platinum chemotherapy. Many ongoing clinical trials and the related progress in adjuvant immunotherapy in early-stage resectable NSCLC are discussed. Furthermore, we highlight several unresolved challenges, including markers predictive of treatment benefit, the efficacy of treatment for some oncogene-addicted tumors, the optimal combination therapy, the duration of adjuvant immunotherapy, and optimal selection between neoadjuvant and adjuvant immunotherapy. Early findings in some clinical trials are promising, and updated overall survival results will be useful for validating the current role of adjuvant immunotherapy, particularly in the context of perioperative strategy.
| S-EPMC9909200 | biostudies-literature
Project description:Lung cancer is the leading cause of cancer deaths in the world. Surgery is the most potentially curative therapeutic option for patients with early-stage non-small cell lung cancer (NSCLC). The five-year survival for these patients remains poor and variable, depending on the stage of disease at diagnosis, and the risk of recurrence following tumor resection is high. During the last 20 years, there has been a modest improvement in the therapeutic strategies for resectable NSCLC. Immune checkpoint inhibitors (ICIs), alone or in combination with chemotherapy, have become the cornerstone for the treatment of metastatic NSCLC patients. Recently, their clinical development has been shifted in the neoadjuvant and adjuvant settings where they have demonstrated remarkable efficacy, leading to improved clinical outcomes. Based on the positive results from phase III trials, ICIs have become a therapeutic option in neoadjuvant and adjuvant settings. On October 2021 the Food and Drug Administration (FDA) approved atezolizumab as an adjuvant treatment following surgery and platinum-based chemotherapy for patients with NSCLC whose tumors express PD-L1 ≥ 1%. In March 2022, nivolumab in combination with platinum-doublet chemotherapy was approved for adult patients with resectable NSCLC in the neoadjuvant setting. The current review provides an updated overview of the clinical trials exploring the role of immunotherapy in patients with early-stage NSCLC, focusing on the biological rationale for their use in the perioperative setting. We will also discuss the role of potential predictive biomarkers to personalize therapy and optimize the incorporation of immunotherapy into the multimodality management of stage I-III NSCLC.
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Project description:BackgroundHistorically, older patients with advanced lung cancer have often received no systemic treatment. Immunotherapy has improved outcomes in clinical trials, but its dissemination and implementation at the population level is not well-understood.MethodsA retrospective cohort study of patients with stage IV non-small cell lung cancer (NSCLC) diagnosed age 66 or older from 2012 to 2015 was conducted using SEER-Medicare. Treatment patterns within one year of diagnosis were ascertained. Outcomes included delivery of (a) any systemic therapy; (b) any second-line infusional therapy, following first-line infusional therapy; and (c) any second-line immunotherapy, following first-line infusional therapy. Trends in care patterns associated with second-line immunotherapy approvals in 2015 were assessed using generalized additive models. Sociodemographic and clinical predictors of treatment were explored using logistic regression.ResultsAmong 10 303 patients, 5173 (50.2%) received first-line systemic therapy, with little change between the years 2012 (47.5%) and 2015 (50.3%). Among 3943 patients completing first-line infusional therapy, the proportion starting second-line infusional treatment remained stable from 2012 (30.5%) through 2014 (32.9%), before increasing in 2015 (42.4%) concurrent with second-line immunotherapy approvals. Factors associated with decreased utilization of any therapy included age, black race, Medicaid eligibility, residence in a high-poverty area, nonadenocarcinoma histology, and comorbidity; factors associated with increased utilization of any therapy included Asian race and Hispanic ethnicity. Among patients who received first-line infusional therapy, factors associated with decreased utilization of second-line infusional therapy included age, Medicaid eligibility, nonadenocarcinoma histology, and comorbidity; Asian race was associated with increased utilization of second-line infusional therapy.ConclusionUnited States Food and Drug Administration (FDA) approvals of immunotherapy for the second-line treatment of advanced NSCLC in 2015 were associated with increased rates of any second-line treatment, but disparities based on social determinants of health persisted.
| S-EPMC7064091 | biostudies-literature
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.
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Project description:BackgroundOur study was designed to determine the safety, efficacy, and immunological effects of perioperative pembrolizumab in early-stage NSCLC.MethodsThis is a single-arm phase II study of perioperative pembrolizumab in patients with untreated, clinical stage IB to IIIA NSCLC. Patients received two doses of 200 mg pembrolizumab, surgery, standard adjuvant chemotherapy, followed by four doses adjuvant pembrolizumab. The primary objective of this study was to determine surgical feasibility rate, and secondary objectives are pathological response rate, treatment adverse events, efficacy data, and exploratory analysis of biomarkers.Results30 patients initiated perioperative pembrolizumab, and 25 completed tumor resection. At median follow-up of 59 months after surgical resection, seven patients had disease progression, while six had died representing. A 5-year progression-free survival (PFS) from time of surgery was 72.0% (56.4%-91.9%) and overall survival (OS) from time of surgery was 75.8% (60.7%-94.7%). Major pathological response (MPR) was found in seven tumors (28%) including two complete responses (4%). Across all treated patients, four receiving neoadjuvant and four receiving adjuvant pembrolizumab experienced treatment-related adverse events of grade 3 or higher with no grade 5 events. Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased across our patient cohort over time from baseline until postsurgery and remained elevated at the end of treatment. There was a significant difference between mean plasma PCSK9 levels for patients with MPR versus all other patients on study when checked postoperatively.ConclusionsPerioperative pembrolizumab was safe and effective with promising MPR rate, PFS, and OS.
| S-EPMC11795402 | biostudies-literature