Long-term benefit of immunotherapy in metastatic non-small cell lung cancer: the tale of the tail
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PROVIDER: S-EPMC10413014 | biostudies-literature | 2023 May
REPOSITORIES: biostudies-literature
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Project description:ObjectiveNovel therapeutics and supportive care improved outcomes for metastatic non-small-cell lung cancer (mNSCLC) patients. Major advances over the past five decades include the introduction of combination chemotherapy, small molecules targeting mutant proteins, especially EGFR, and more recently immunotherapy. We aim to document real-world long-term survival over the past five decades.MethodsSurvival statistics were extracted from the Survival, Epidemiology, and End Results (SEER) database for mNSCLC patients during 1973-2015. Two- and five-year survival (2yS and 5yS) were analyzed using Kaplan-Meier and proportional hazard models.ResultsThe study population consisted of 280,655mNSCLC patients diagnosed during 1973-2015. Longer survival was seen in younger, female, married, Asian/Pacific Islander race, adenocarcinoma, lower grade, more recent diagnosis, higher income, and chemotherapy-treated patients. 2yS increased during the study period from 2.6% to 12.9%, and 5yS increased from 0.7% to 3.2%. 2yS of patients <50 years of age rose from 2.1% to 22.8%, and their 5yS rose from 0.7% to 6.2%. 2yS of adenocarcinoma patients improved from 2.7% to 16.2%, and their improved 5yS from 1.1% to 3.9%.ConclusionsBetween 1973 and 2015, there was a dramatic improvement in long-term survival, with an approximately five-fold increase in both 2yS and 5yS. Nonetheless, absolute numbers of long-term survivors remained low, with less than 4% living 5 years. This provides a baseline to compare long-term outcomes seen in the current generation of clinical trials.
| S-EPMC7817269 | biostudies-literature
Project description:High heterogeneity in clinical benefit characterizes the use of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We prospectively enrolled 113 advanced NSCLC patients treated with ICIs and performed liquid biopsy at the time of ICI start (T1), after 3 weeks (T2) and at the time of radiological evaluation (T3). Molecular variables were associated with outcome endpoints: cfDNA quantification, its dynamic change (∆T2-T1), variant allele frequency (VAF) of the gene with the highest frequency detected at baseline with NGS (maxVAF) and its dynamic change (∆T2-T1). At multivariate analysis, PD-L1 negativity, T1 cfDNA, cfDNA increase (∆T2-T1), and T2 VAF were significantly associated with shorter progression-free survival (PFS); PD-L1 negativity, squamous histology, T1 cfDNA, cfDNA (∆T2-T1) increase, and T2 maxVAF affected overall survival (OS). Among high PD-L1 expressing patients treated in first-line, elevated T2 maxVAF and cfDNA increase (∆T2-T1) correlated with worse PFS; higher T2 maxVAF and cfDNA increase (∆T2-T1) with worse OS. Derived integrated models were used to build nomograms and categorize different risk groups.
| S-EPMC11486993 | biostudies-literature
Project description:For patients with advanced non-small-cell lung cancer (nsclc) lacking a targetable molecular driver, the mainstay of treatment has been cytotoxic chemotherapy. The survival benefit of chemotherapy in this setting is modest and comes with the potential for significant toxicity. The introduction of immunotherapeutic agents targeting the programmed cell death 1 protein (PD-1) and the programmed cell death ligand 1 (PD-L1) has drastically changed the treatment paradigms for these patients. Three agents-atezolizumab, nivolumab, and pembrolizumab-have been shown to be superior to chemotherapy in the second-line setting. For patients with tumours strongly expressing PD-L1, pembrolizumab has been associated with improved outcomes in the first-line setting. Demonstration of the significant benefits of immunotherapy in nsclc has focused attention on new questions. Combination checkpoint regimens, with acceptable toxicity and potentially enhanced efficacy, have been developed, as have combinations of immunotherapy with chemotherapy. In this review, we focus on the published trials that have changed the treatment landscape in advanced nsclc and on the ongoing clinical trials that offer hope to further improve outcomes for patients with advanced nsclc.
| S-EPMC6001755 | biostudies-literature
Project description:Although adoptive immunotherapy (AIT) is a novel emerging target treatment for non-small cell lung cancer (NSCLC), its actual efficacy remains controversial. In this meta-analysis, we aimed to evaluate the efficacy of AIT for NSCLC. We systematically searched PubMed, the Cochrane Library, EMBASE, Medline, and Web of Science for relevant parallel randomized controlled trials (RCTs) and high-quality observation studies of AIT without any language restrictions. Two investigators reviewed all the texts and extracted information regarding overall survival rate (OS), progression-free survival rate (PFS), objective response rate (ORR), and disease control rate (DCR) from eligible studies; sensitivity analyses and subgroup analyses were also conducted to reduce heterogeneity Of 319 suitable studies, 15 studies (13 RCTs and 2 observation studies) involving 1684 patients were finally included. Compared to the Control therapy (CT) group, the AIT group exhibited better 1-year OS (P = 0.001), 2-year OS (P < 0.001), 3-year OS (P < 0.001), 5-year OS (P = 0.032), 1-year PFS (P < 0.001), and 2-year PFS (P = 0.029). The difference in the ORR (P = 0.293) and DCR (P = 0.123) was not significant between the groups. The subgroup analysis showed that DC/CIK did more benefit to NSCLC patients than LAK and the cycles not associated with AIT efficacy. AIT can significantly improve the OS and PFS with acceptable toxicity for NSCLC. Nevertheless, further multicenter studies are needed to confirm our conclusion and determine which adoptive immunotherapy is associated with the greatest efficacy.
| S-EPMC5762575 | biostudies-literature
Project description:BackgroundThe use of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer is increasing. Despite ongoing studies to predict the efficacy of ICIs, its use in clinical practice remains difficult. Thus, we aimed to discover a predictive marker by analyzing blood cell characteristics and developing a scoring system for patients treated with ICIs.MethodsThis was a prospective multicenter study in patients with advanced nonsmall cell lung cancer (NSCLC) who received ICIs as second-line treatment from June 2021 to November 2022. Blood cell parameters in routine blood samples were evaluated using an automated hematology analyzer. Immune checkpoint inhibitor score (IChIS) was calculated as the sum of neutrophil count score and immature granulocyte score.ResultsA total of 143 patients from four institutions were included. The treatment response was as follows: partial response, 8.4%; stable disease, 37.1%; and progressive disease, 44.8%. Median progression-free survival and overall survival after ICI treatment was 3.0 and 8.3 months, respectively. Median progression-free survival in patients with an IChIS of 0 was 4.0 months, which was significantly longer than 1.9 months in patients with an IChIS of 1 and 1.0 month in those with an IChIS of 2 (p=0.001). The median overall survival in patients with an IChIS of 0 was 10.2 months, which was significantly longer than 6.8 and 1.8 months in patients with an IChIS of 1 and 2, respectively (p<0.001).ConclusionBaseline IChIS could be a potential biomarker for predicting survival benefit of immunotherapy in NSCLC.
| S-EPMC11468437 | biostudies-literature
Project description:Circulating tumor DNA (ctDNA) molecular residual disease (MRD) following curative-intent treatment strongly predicts recurrence in multiple tumor types, but whether further treatment can improve outcomes in patients with MRD remains unclear. We applied CAPP-Seq ctDNA analysis to 218 samples from 65 patients receiving chemoradiation therapy (CRT) for locally advanced NSCLC, including 28 patients receiving consolidation immune checkpoint inhibition (CICI). Patients with undetectable ctDNA after CRT had excellent outcomes whether or not they received CICI. Among such patients, one died from CICI-related pneumonitis, highlighting the potential utility of only treating patients with MRD. In contrast, patients with MRD after CRT who received CICI had significantly better outcomes than patients who did not receive CICI. Furthermore, the ctDNA response pattern early during CICI identified patients responding to consolidation therapy. Our results suggest that CICI improves outcomes for NSCLC patients with MRD and that ctDNA analysis may facilitate personalization of consolidation therapy.
| S-EPMC8425388 | biostudies-literature
Project description:PurposeBrain metastases (BMs) are common in Small Cell Lung Cancer (SCLC), but the prognosis is very poor. Currently, there is no standard of care on what constitutes optimal treatment, and there is no consensus regarding maintenance therapy in SCLC.Case descriptionWe report the case of a 55-year-old man with advanced SCLC. After the initial diagnosis, he received routine chemotherapy and chest radiotherapy but developed brain metastases with 2 lesions seven months later. We used an effective combination therapy consisting of the antiangiogenic inhibitor, Anlotinib and whole-brain radiotherapy. We then administered anti-PD-L1 immunotherapy Atezolizumab in combination with Anlotinib as long-term maintenance therapy. Twelve months later, there was a progression in one of the brain metastases. The patient underwent further stereotactic radiotherapy (SRT) for the lesion. However, after four months of treatment with SRT, the lesion began to gradually grow in size. The patient underwent surgical resection of the lesion, which confirmed radioactive brain necrosis. After a full 3-year course of anti-PD-L1 therapy, the patient discontinued immunotherapy and was administered only Anlotinib as maintenance. At the time of writing up this report, the patient was alive and the overall survival reached 41 months after the onset of BM.ConclusionThis indicated a potential synergistic effect of combined immunotherapy and antiangiogenic targeted therapy with local radiotherapy in patients with BM-SCLC and can provide directions for future clinical decisions.
| S-EPMC10587576 | biostudies-literature
Project description:BackgroundCombining radiotherapy (RT) and immunotherapy (IT) may enhance outcomes for metastatic non-small cell lung cancer (mNSCLC). However, data on the immunomodulatory effects of extracranial RT remains limited. This retrospective database analysis examined real-world practice patterns, predictors of survival, and comparative effectiveness of extracranial radioimmunotherapy (RT + IT) versus early-incorporation immunotherapy (eIT) in patients with mNSCLC.MethodsPatients diagnosed with mNSCLC between 2004-2016 treated with eIT or RT + IT were identified in the National Cancer Database. Practice patterns were assessed using Cochrane-Armitrage trend test. Cox proportional hazards and Kaplan-Meier method were used to analyze overall survival (OS). Propensity score matching was performed to account for baseline imbalances. Biologically effective doses (BED) were stratified based on the median (39 Gy10). Stereotactic body radiotherapy (SBRT) was defined as above median BED in ≤5 fractions.ResultseIT utilization increased from 0.3% in 2010 to 13.2% in 2016 (P<0.0001). Rates of RT + eIT increased from 38.8% in 2010 to 49.1% in 2016 among those who received eIT (P<0.0001). Compared to eIT alone, RT + eIT demonstrated worse median OS (11.2 vs. 13.2 months) while SBRT + eIT demonstrated improved median OS (25 vs. 13.2 months) (P<0.0001). There were no significant differences in OS based on sequencing of eIT relative to RT (log-rank P=0.4415) or irradiated site (log-rank P=0.1606). On multivariate analysis, factors associated with improved OS included chemotherapy (HR 0.86, P=0.0058), treatment at academic facilities (HR 0.83, P<0.0001), and SBRT (HR 0.60, P=0.0009); after propensity-score multivariate analysis, SBRT alone showed improved OS (HR 0.28, P<0.0001).ConclusionsUtilization of RT + eIT in mNSCLC is increasing. SBRT + eIT was associated with improved OS on propensity-score matched analysis. There were no significant differences in OS based on RT + eIT sequencing or site irradiated. Whether these observations reflect patient selection or possible immunomodulatory benefits of RT is unclear and warrants further study.
| S-EPMC7867754 | biostudies-literature
Project description: Not available
| S-EPMC10923855 | biostudies-literature
Project description:Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/- ramucirumab n=381; platinum/taxane-based regimens n=73). Progression-free survival (PFS) and overall survival (OS) were compared among different subpopulations with different cancer gene mutations and between patients who received docetaxel +/- ramucirumab versus platinum/taxane-based regimens. Among patients who received docetaxel +/- ramucirumab, the top mutated cancer genes included TP53 (n=167), KRAS (n=127), EGFR (n=65), STK11 (n=32), ERBB2 (HER2) (n=26), etc. None of these cancer gene mutations or PD-L1 expression was associated with PFS or OS. Platinum/taxane-based regimens were associated with a significantly longer mQS (13.00 m, 95% Cl: 11.20-14.80 m versus 8.40 m, 95% Cl: 7.12-9.68 m, LogRank P=0.019) than docetaxel +/- ramcirumab. Key prognostic factors including age, histology, and performance status were not different between these two groups. In conclusion, in patients with metastatic NSCLC who have progressed on platinum doublets and ICIs, the clinical benefit from docetaxel +/- ramucirumab is not associated with the cancer gene mutation status. Platinum/taxane-based regimens may offer a superior clinical benefit over docetaxel +/- ramucirumab in this patient population.
| S-EPMC10931294 | biostudies-literature