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Neoadjuvant and consolidation immuno-oncology therapy in stage III non-small cell lung cancer.

ABSTRACT: Lung cancer continues to be the leading cause of cancer death worldwide. Recently, immunotherapy for non-small cell lung cancer (NSCLC) has emerged as a powerful treatment option for advanced lung cancer. The relative success of programmed death 1 (PD-1) and/or programmed death ligand 1 (PD-L1) antibodies in metastatic disease have increased interest in expanding their use to earlier stage NSCLC. The complex and diverse nature of stage III disease also invites the incorporation of immunotherapy into treatment plans in both the neoadjuvant and consolidation settings. Currently available data of anti-PD-(L)1 therapies in stage III NSCLC are limited. However, interim results from two studies are encouraging: a phase II neoadjuvant nivolumab trial demonstrated early signals of efficacy, and the phase III PACIFIC trial of durvalumab recently showed significant improvement in progression-free survival (PFS). Preliminary results for the phase II DETERRED trial of durvalumab have also been reported. Many studies are testing anti-PD-(L)1 therapies in the neoadjuvant and consolidation settings for stage III NSCLC, and will be discussed. As these studies mature they may provide further treatment options in management of stage III NSCLC.

SUBMITTER: Yeh J

PROVIDER: S-EPMC5861269 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Neoadjuvant and consolidation immuno-oncology therapy in stage III non-small cell lung cancer.

Yeh Justin J Marrone Kristen A KA Forde Patrick M PM

Journal of thoracic disease 20180201 Suppl 3

Lung cancer continues to be the leading cause of cancer death worldwide. Recently, immunotherapy for non-small cell lung cancer (NSCLC) has emerged as a powerful treatment option for advanced lung cancer. The relative success of programmed death 1 (PD-1) and/or programmed death ligand 1 (PD-L1) antibodies in metastatic disease have increased interest in expanding their use to earlier stage NSCLC. The complex and diverse nature of stage III disease also invites the incorporation of immunotherapy ...[more]

PMID: 29593890

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Project description:BackgroundThis open, observational clinical study aimed to investigate the efficacy, safety and survival outcomes of neoadjuvant chemotherapy, neoadjuvant immunotherapy with(out) chemotherapy and neoadjuvant targeted therapy among resectable stage III non-small cell lung cancer (NSCLC) patients (NCT04197076) in real world. 48 of the 57 evaluable patients were included in this interim analysis.MethodsThis study was conducted at Shanghai Chest Hospital and included eligible NSCLC patients who were 18 years or older and had resectable clinical stage III disease. Surgical resection was conducted after neoadjuvant chemotherapy (13 patients), immunotherapy with(out) chemotherapy (26 patients), and targeted therapy (9 patients). Disease-free survival (DFS) was evaluated as the primary endpoint. The secondary endpoint was pathological complete response (pCR) rate. Clinical response rate (cRR), related adverse events (AEs), surgical feasibility and pathological features were also discussed in this study.ResultsSignificant differences in DFS were noted between chemotherapy and immunotherapy [7.7 months (range, 3.1 to 23.2 months) vs. 9.6 months (range, 4.0 to 47.9 months); P=0.032], and between chemotherapy and targeted therapy [7.7 months (range, 3.1 to 23.2 months) vs. 13.2 months (range, 7.5 to 32.2 months); P=0.015], but not between immunotherapy and targeted therapy (P=0.500). Subgroup analysis also favored neoadjuvant immunotherapy and targeted therapy. 5 patients achieved pathological complete response (pCR), all of whom were in the neoadjuvant immunotherapy arm, leading to a pCR rate of 19.2% in this arm. Treatment-emergent adverse events (TEAEs) of over grade 3 occurred in 11 patients (19.3%), with 5 (29.4%) in the chemotherapy arm, 5 (16.7%) in the immunotherapy arm and 1 (10.0%) in the targeted therapy arm. One grade 4 and one grade 2 surgery-related serious adverse event occurred in the neoadjuvant chemotherapy and immunotherapy arm, respectively.ConclusionIn patients diagnosed with resectable stage III NSCLC, neoadjuvant immunotherapy and neoadjuvant targeted therapy were associated with significantly longer disease-free survival compared with neoadjuvant chemotherapy. Clinical and pathological response rates were also higher in the immunotherapy and targeted therapy arm. Adverse events were found to be manageable and similar across all three groups, and surgical feasibility favored immunotherapy or targeted therapy rather than chemotherapy.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04197076.

Project description:BackgroundStage III Non-small cell lung cancer (NSCLC) is a heterogenous disease with novel treatment options. Recently, immunotherapy has attracted a lot of attention for advanced NSCLC.ObjectiveThe objective of our study was to assess the efficacy and safety of neoadjuvant immuno-chemotherapy for resectable stage III NSCLC.MethodsWe analyzed 11 stage III primary NSCLC surgical cases who had undergone standard lobectomy or bronchial sleeve resection and lymph node dissection between December 2020 and July 2021. The data analyzed included basic clinical features, serum levels of key biomarkers, clinical efficacy in the perioperative period, postoperative pathological results, postoperative complications and the incidence rates of Immune-Related Adverse Events.ResultsEleven patients were enrolled in our study with a mean age of 67.7 ± 4.8 years, and 10 patients being men with former or current smoking history. Squamous carcinoma (10/11, 91.1%) was the most common cancer type. Six patients had stage IIIa, five had stage IIIb. All patients received two or three cycles of neoadjuvant immuno-chemotherapy, with the median duration between the last treatment and surgery being 39 days (range, 32-46 days). All patients underwent R0 resection with ten patients undergoing single-port video-assisted thoracoscopic surgery. The median operative time was 170 min (range, 120-240 min). Only three (3/11, 27.3%) patients experienced mild postoperative complications and the mean hospital stay time was 6.9 days (range, 4-15 days). Nine (9/11, 81.8%) patients experienced major pathological response of which seven (7/11, 63.6%) was complete pathological response in postoperative results. The pathological stage was downgraded in 10 (10/11, 91.1%) patients, and although the incidence of Immune-Related Adverse Events was slightly higher (8/11, 72.7%), most events were grade 1-2 and did not delay surgery.ConclusionOur study demonstrated that neoadjuvant immuno-chemotherapy is feasible and relatively safe for resectable stage III primary NSCLC patients. We hope this new neoadjuvant immuno-chemotherapy model can improve overall survival and open a new era for stage III primary NSCLC patients.

Project description:BackgroundStage III non-small cell lung cancer (NSCLC) is a heterogeneous disease with different subtypes, multidisciplinary teams-led management, and a poor prognosis. Currently, the clinical benefits of stage III NSCLC in the neoadjuvant setting are still unclear. We performed a meta-analysis of published data on neoadjuvant chemoimmunotherapy in stage III NSCLC to systematically evaluate its efficacy and safety.MethodsWe searched the databases to identify eligible studies of neoadjuvant chemoimmunotherapy for stage III NSCLC. The primary outcomes mainly included pathological and radiological response outcomes, the feasibility of surgery, and the safety of the regimen. The pathological and radiological response included the rate of major pathologic response (MPR), complete pathologic response (pCR), radiological response outcomes, and R0 resection; The feasibility included the rate of surgical resection, conversion to thoracotomy, surgical complications, pathological downstaging of clinical disease stage. The safety included the incidence of treatment-related adverse events (TRAEs) and severe adverse events (SAEs). R 4.1.3 software was conducted for data analysis, and p < 0.05 was considered statistically significant.ResultsNine trials containing a total of 382 populations were eligible for the meta-analysis, with the pooled surgical resection rate of 90%. Owing to the large heterogeneity of the single-rate meta-analysis, the random effect model was adopted. The estimated pooled prevalence of MPR was 56% (95%CI 0.39-0.72) and of pCR was 39% (95%CI 0.28-0.51). The pooled rate of TRAEs was 65% (95%CI 0.17-0.99) and SAEs was 24% (95%CI 0.05-0.49).ConclusionCompared to neoadjuvant chemotherapy or immunotherapy, neoadjuvant chemoimmunotherapy achieved more pathological and radiological relief, and has a high surgical resection rate and low risk of conversion to thoracotomy and surgical complications, with poor tolerance of toxicity but rarely developing life-threatening adverse events. In conclusion, neoadjuvant chemoimmunotherapy is suggested to be beneficial for stage III NSCLC.

Project description:ImportanceIn early 2018, durvalumab became the first immunotherapy to be approved for adjuvant treatment of patients with unresectable stage III non-small cell lung cancer (NSCLC) whose cancer has not progressed after definitive chemoradiotherapy. However, the cost-effectiveness and potential economic implications of using this high-priced therapy in this indication are unknown to date.ObjectiveTo explore the cost-effectiveness and potential budgetary consequences of durvalumab consolidation therapy vs no consolidation therapy after chemoradiotherapy in stage III NSCLC in the context of the US health care system.Design, setting, and participantsA decision analytic microsimulation model was developed in an academic medical setting to compare the following 2 postchemoradiotherapy strategies: all patients receive no consolidation therapy until progression vs all patients receive durvalumab consolidation therapy until progression or for a maximum of 1 year. The potential budgetary consequence was calculated by applying the proportion of patients with NSCLC who were diagnosed in stage III and received chemoradiotherapy to the projected number of annual new cases for 2018 to 2022 to find total eligible patients and then multiplied by the mean difference in annual cost between the strategies over this 5-year period. Simulated conditions were matched to those of the PACIFIC phase 3 randomized clinical trial and reasonable treatment strategies for metastatic NSCLC. All simulated patients begin disease free after having received radical treatment with chemoradiotherapy and are followed up as they progress to metastatic disease first-line treatment, metastatic disease second-line treatment, end-stage progressive disease, and death.Main outcomes and measuresThe main outcome of this study was the incremental cost-effectiveness ratio of durvalumab consolidation therapy vs no consolidation therapy, given as aggregate cost of treatment per quality-adjusted life-year gained.ResultsAmong 2 million simulated patients, durvalumab consolidation therapy was cost-effective compared with no consolidation therapy at a $100 000 per quality-adjusted life-year willingness-to-pay threshold, with an estimated incremental cost-effectiveness ratio of $67 421 per quality-adjusted life-year, and would contribute an additional $768 million to national cancer spending in year 1. The annual budgetary consequence would then decrease to $241 million in year 5.Conclusions and relevanceDurvalumab consolidation therapy represents an indication where expensive immunotherapies can be cost-effective. Treating with immunotherapy earlier in the course of cancer progression can provide significant value, despite having a substantial budgetary consequence.

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Neoadjuvant and consolidation immuno-oncology therapy in stage III non-small cell lung cancer.

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Neoadjuvant and consolidation immuno-oncology therapy in stage III non-small cell lung cancer.

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