Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC-Real World Efficacy.
Ontology highlight
ABSTRACT:
SUBMITTER: Mouritzen MT
PROVIDER: S-EPMC8507718 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Introduction Pembrolizumab plus carboplatin and (nab-)paclitaxel (pembrolizumab-chemotherapy) is currently an approved and recommended systemic therapy for patients with previously untreated advanced squamous NSCLC. This retrospective study evaluated real-world time on treatment (rwToT) and overall survival (OS) among patients with advanced squamous NSCLC treated with first-line pembrolizumab-chemotherapy at oncology practices in the United States. Methods Using a real-world database, we selected adult patients with newly diagnosed or recurrent advanced squamous NSCLC (unresectable stages IIIB, IIIC, or IV) and good performance status (Eastern Cooperative Oncology Group 0–1) who initiated first-line pembrolizumab-chemotherapy from November 1, 2018, to May 31, 2020. The Kaplan-Meier method was used to determine rwToT and OS overall and by programmed death-ligand 1 (PD-L1) expression. Data cutoff was October 31, 2021. Results Of 364 eligible patients, 243 (67%) were men; median age was 70 (range: 43–84) years; and PD-L1 expression was greater than or equal to 1%, less than 1%, and unknown for 172 (47%), 94 (26%), and 98 patients (27%), respectively. Median follow-up from pembrolizumab-chemotherapy initiation to data cutoff was 26.2 months. Overall, median pembrolizumab rwToT was 6.5 months (95% confidence interval [CI]: 5.6–7.6), with on-treatment rates of 29.3% and 15.9% at 12 and 24 months, respectively. Median OS was 15.3 months (95% CI: 11.7–18.6), with 12- and 24-month OS rates of 54.9% and 37.3%, respectively. Median OS did not differ with PD-L1 expression: 16.2 months (95% CI: 10.3–20.6) for PD-L1 greater than or equal to 1% and 17.2 months (95% CI: 10.8–20.6) for PD-L1 less than 1%. Conclusions For patients with advanced squamous NSCLC and good performance status treated with first-line pembrolizumab-chemotherapy, rwToT and OS are similar to clinical trial findings for treatment duration and OS.
| S-EPMC9900616 | biostudies-literature
Project description:BackgroundThere have been no comprehensive large-scale studies that have evaluated the benefits of chemotherapy-based regimens in addressing HER2-altered advanced non-small-cell lung cancer (NSCLC) in a first-line setting. Data on HER2 alteration subtypes and concomitant alterations are also limited. Accordingly, our retrospective, real-world POLISH study assesses the efficacy of first-line chemotherapy alone (C) as well as combinations with immune checkpoint inhibitors (C + I) or angiogenesis inhibitors (C + A) for HER2-altered NSCLC; molecular features are also reported.MethodsHER2-altered NSCLC patients who received a first-line treatment between November 2015 and September 2021 were screened. Patients treated with C, C + I, or C + A were included in our final efficacy analysis. Progression-free survival (PFS) was compared between the subgroups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to evaluate concomitant alterations.ResultsA total of 293 patients were screened, with an identification of HER2 amplification and 37 distinct HER2 mutations, and 210 cases treated with C, C + I, or C + A were ultimately included. C + A achieved longer PFS than C (5.63 vs 4.03 months, hazard ratio: 0.64, 95% confidence interval [CI]: 0.46-0.88, p = 0.006). C + I did not improve median PFS compared to C + A or C (both p > 0.05), despite the programmed cell death ligand-1 (PD-L1) expression or tumor mutational burden. KEGG analysis revealed that concomitant upregulation of PI3 K/AKT pathway signaling was common in HER2-altered NSCLC.ConclusionChemotherapy plus angiogenesis inhibitors may yield a greater survival benefit than chemotherapy alone in a first-line setting for HER2-altered NSCLC, whereas an immune-based combination therapy may not be superior to a sole chemotherapy regimen. Activation of PI3 K/AKT signaling may mediate immunosuppression in HER2-altered NSCLC.
| S-EPMC8894956 | biostudies-literature
Project description:IntroductionData on utilization and clinical outcomes of programmed cell death protein or programmed death-ligand 1 (PD-[L]1) inhibitors in NSCLC with uncommon oncogenic alterations is limited.MethodsThis retrospective study used a deidentified U.S. nationwide clinicogenomic database to select patients with advanced nonsquamous NSCLC without EGFR, ALK, or ROS1 alterations, diagnosed from January 1, 2016 to September 30, 2020, who initiated first-line therapy. Our objectives were to summarize characteristics and treatment patterns for patients with four little-studied genomic alterations or driver-negative NSCLC. We estimated Kaplan-Meier real-world time on treatment (rwTOT) and time to next treatment for patients receiving PD-(L)1 inhibitors. The data cutoff was September 30, 2021.ResultsOf the 3971 eligible patients, 84 (2%) had NSCLC with BRAF V600E mutation, 117 (3%) had MET exon 14 skipping mutation, 130 (3%) had MET amplification, 91 (2%) had ERBB2 activation mutation, and 691 patients (17%) had driver-negative NSCLC. Patient characteristics differed among cohorts as expected. The most common first-line regimen in each cohort was a PD-(L)1 inhibitor as monotherapy or in combination with chemotherapy. The median rwTOT with anti-PD-(L)1 monotherapy was 4.6 months in the driver-negative cohort and ranged from 2.9 months (ERBB2 mutation) to 7.6 months (BRAF V600E mutation). The median rwTOT with anti-PD-(L)1-chemotherapy combination was 5.2 months in the driver-negative cohort and 6 months in all but the BRAF V600E cohort (17.5 mo). The patterns of real-world time to next treatment results were similar.ConclusionsSubstantial use of anti-PD-(L)1 therapy and associated clinical outcomes are consistent with previous real-world findings and suggest no detriment from PD-(L)1 inhibitors for advanced nonsquamous NSCLC harboring one of these four genomic alterations relative to driver-negative NSCLC.
| S-EPMC10514206 | biostudies-literature
Project description:BackgroundMany studies have compared real-world clinical outcomes of immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC) with reported outcomes data from pivotal trials. However, any differences observed could be only limitedly explored further for causation because of the unavailability of individual patient data (IPD) from trial participants. The present study aims to explore the additional benefit of comparison with IPD.MethodsThis study compares progression free survival (PFS) and overall survival (OS) of metastatic NSCLC patients treated with second line nivolumab in real-world clinical practice (n = 141) with IPD from participants in the Checkmate-057 clinical trial (n = 292). Univariate and multivariate Cox proportional hazards models were used to construct HRs for real-world practice versus clinical trial.ResultsReal-world patients were older (64 vs. 61 years), had more often ECOG PS ≥ 2 (5 vs. 0%) and were less often treated with subsequent anti-cancer treatment (28.4 vs. 42.5%) compared to trial patients. The median PFS in real-world patients was longer (3.84 (95%CI: 3.19-5.49) vs 2.30 (2.20-3.50) months) and the OS shorter than in trial participants (8.25 (6.93-13.2) vs. 12.2 (9.90-15.1) months). Adjustment with available patient characteristics, led to a shift in the hazard ratio (HR) for OS, but not for PFS (HRs from 1.13 (0.88-1.44) to 1.07 (0.83-1.38), and from 0.82 (0.66-1.03) to 0.79 (0.63-1.00), respectively).ConclusionsThis study is an example how IPD from both real-world and trial patients can be applied to search for factors that could explain an efficacy-effectiveness gap. Making IPD from clinical trials available to the international research community allows this.
| S-EPMC9807419 | biostudies-literature
Project description:BackgroundCurrently, limited data on targeted therapy and immunotherapy sequencing in patients with BRAF-mutant melanoma is available. Targeted therapy and immunotherapy are expected to be comparable in terms of overall survival (OS) when used as second-line therapies; therefore, understanding the characteristics of patients who completed sequential treatment is needed.MethodsThe primary objective of this study was to analyze the efficacy of BRAFi/MEKi activity as second-line therapy in patients with advanced melanoma. We also aimed to describe the clinical characteristics of patients with advanced melanoma who were treated sequentially with immunotherapy and targeted therapy. We enrolled 97 patients treated between 1st December 2015 and 31st December 2020 with first-line immunotherapy with programmed cell death 1 (PD-1) checkpoint inhibitors; and for the second-line treatment with at least one cycle of BRAFi/MEKi therapy with follow-up through 31 January 2022.ResultsMedian OS since first-line treatment initiation was 19.9 months and 12.8 months since initiation of BRAFi/MEKi treatment. All BRAFi/MRKi combinations were similarly effective. Median progression free survival (PFS) was 7.5 months since initiation of any BRAFi/MEKi treatment.ConclusionsBRAFi/MEKi therapy is effective in the second-line in advanced and metastatic melanoma patients. For the first time, the efficacy of all BRAFi/MEKi combinations as second-line therapy is shown.
| S-EPMC9032972 | biostudies-literature
Project description:Background & objective"Anti-angiogenetic drugs plus chemotherapy" (anti-angio-chemo) and "immune checkpoint inhibitors plus chemotherapy" (ICI-chemo) are superior to traditional chemotherapy in the first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). However, in the absence of a direct comparison of ICI-chemo with anti-angio-chemo, the superior one between them has not been decided, and the benefit of adding anti-angiogenetic agents to ICI-chemo remains controversial. This study aimed to investigate the role of antiangiogenic agents for advanced NSCLC in the era of immunotherapy.MethodsEligible randomized controlled trials (RCTs) comparing chemotherapy versus therapeutic regimens involving ICIs or anti-angiogenetic drugs were included. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and rate of grade 3-4 toxicity assessment. R-4.3.1 was utilized to perform the analysis.ResultsA total of 54 studies with a sample size of 25,046 were finally enrolled. "Atezolizumab + Bevacizumab + Chemotherapy" significantly improved the ORR compared with "Atezolizumab + Chemotherapy" (Odds ratio (OR) = 2.73, 95% confidence interval (CI): 1.27-5.87). The trend also favored "Atezolizumab + Bevacizumab + Chemotherapy" in PFS and OS (hazard ratio (HR) = 0.71, 95% CI: 0.39-1.31; HR = 0.94, 95% CI: 0.77-1.16, respectively). In addition, "Pembrolizumab + Chemotherapy" and "Camrelizumab + Chemotherapy" significantly prolonged the PFS compared to "Bevacizumab + Chemotherapy" (HR = 0.65, 95% CI: 0.46-0.92; HR = 0.63, 95% CI: 0.41-0.97; respectively). Meanwhile, "Pembrolizumab + Chemotherapy" and "Sintilimab + Chemotherapy" yielded more OS benefits than "Bevacizumab + Chemotherapy" (HR = 0.69, 95% CI: 0.56-0.83; HR = 0.64, 95%CI: 0.46-0.91; respectively). Scheme between "Atezolizumab + Bevacizumab + Chemotherapy" and "Atezolizumab + Chemotherapy" made no significant difference (OR = 1.18, 95%CI: 0.56-2.42) concerning the rate of grade 3-4 toxicity. It seemed that ICI-chemo yielded more improvement in quality-adjusted life-year (QALY) than "Bevacizumab + Chemotherapy" in cost-effectiveness analysis.ConclusionOur results suggest that ICI-chemo is associated with potentially longer survival, better cost-effectiveness outcomes, and comparable safety profiles than anti-angio-chemo. Also, adding bevacizumab to ICI-chemo seemed to provide additional therapeutic benefits without adding treatment burden. Our findings would supplement the current standard of care and help the design of future clinical trials for the first-line treatment of patients with advanced NSCLC.
| S-EPMC9862794 | biostudies-literature
Project description:Background and objectivesEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard-of-care first-line (1L) treatment for EGFR mutation-positive advanced/metastatic non-small cell lung cancer. In 2015, osimertinib, a third-generation EGFR-TKI, received US accelerated approval for second-line (2L) EGFR T790M-positive non-small cell lung cancer treatment. The objective of this US study was to characterize treatment patterns, attrition, and survival in EGFR mutation-positive non-small cell lung cancer, after 1L first-/second-generation EGFR-TKI treatment.MethodsWe retrospectively analyzed 1029 patients diagnosed with stage IIIB/IV non-small cell lung cancer from 1 January, 2011 to 31 December, 2018 using the US electronic medical record CancerLinQ Discovery® database. Demographic/disease characteristics, EGFR mutations, treatments, and death dates were collected.ResultsFrom 1 January, 2011 to 31 December, 2014 (< 2015 cohort), 519 patients received 1L EGFR-TKIs and 510 between 1 January, 2015 and 31 December, 2018 (≥ 2015 cohort). Median follow-up from advanced diagnosis was 19.8 months (interquartile range: 9.9-33.4 months). Twenty-eight percent of patients (288/1029) died without receiving 2L, and 52% (539/1029) initiated 2L with 35% (186/539) receiving osimertinib; in the < 2015 and ≥ 2015 cohorts, the same proportion initiated 2L (52%; 272/519 vs 267/510, respectively). Median overall survival from advanced diagnosis for patients initially diagnosed with stage I-IIIA disease was 43.3 months (95% confidence interval 30.9-73.7), vs 26.4 months (95% confidence interval 24.4-28.1) for stage IIIB-IV; all-cause mortality hazard ratio: 1.56 (95% confidence interval 1.2-2.0; p = 0.001).ConclusionsWe identified disease stage, performance status, and central nervous system metastasis as survival predictors, highlighting the importance of optimal 1L treatment selection. Over a quarter of patients died before initiating 2L; half progressed after 1L and received 2L, of whom a third received 2L osimertinib.
| S-EPMC9392819 | biostudies-literature
Project description:BackgroundThis study was to investigate the influence of GSTP1 gene polymorphism on the clinical outcomes of patients with advanced non-small-cell lung cancer (NSCLC) receiving first-line bevacizumab plus chemotherapy regimen.MethodsA total of 128 patients with advanced NSCLC who were administered with bevacizumab-based first-line regimens were recruited in this study. Available blood specimen and peripheral blood mononuclear cells (PBMCs) of the patients were obtained for the analysis of polymorphism and GSTP1 gene mRNA expression, respectively. The association between genotype status and clinical outcomes and other variates was analyzed and presented.ResultsThe prevalence of rs1695 were in accordance with Hardy-Weinberg Equilibrium (P = .978). Patients with GG and AG genotypes were merged in a pattern of dominant inheritance to seek for the potentially clinical significance. Analysis of efficacy exhibited that the objective response rate (ORR) of patients with AA genotype and AG/GG genotypes were 62.1% (54/87) and 51.2% (21/41) (P = 0.245). Prognosis demonstrated that the median progression-free survival (PFS) of patients with AA genotype and AG/GG genotypes were 9.5 and 5.6 months, respectively (P = .007). Furthermore, the median overall survival (OS) of the two genotypes were 22.0 and 16.6 months, respectively (P = .003). In addition, adjusted in multivariate Cox analysis for OS, AG/GG genotype was an independent factor for OS. Interestingly, mRNA analysis suggested that the mRNA expression of GSTP1 in PBMC of the patients with AG/GG genotypes of rs1695 polymorphism was significantly higher than those of patients with AA genotype (P < .001).ConclusionGSTP1 polymorphism rs1695 could be used for the prognostic evaluation of patients with advanced NSCLC receiving bevacizumab combined chemotherapy regimen.
| S-EPMC8679038 | biostudies-literature
Project description:Evidence from real-world clinical settings is lacking with regard to first-line immunotherapy plus chemotherapy for the treatment of non-small cell lung cancer (NSCLC). Our aim was to describe outcomes for patients treated with first-line pembrolizumab-combination therapy for metastatic nonsquamous NSCLC in US oncology practices. Using an anonymized, nationwide electronic health record-derived database, we identified patients who initiated pembrolizumab plus pemetrexed-carboplatin in the first-line setting (May 2017 to August 2018) after diagnosis of metastatic nonsquamous NSCLC that tested negative for EGFR and ALK genomic aberrations. Eligible patients had ECOG performance status of 0-1. An enhanced manual chart review was used to collect outcome information. Time-to-event analyses were performed using the Kaplan-Meier method. Of 283 eligible patients, 168 (59%) were male; median age was 66 years (range 33-84); and the proportions of patients with PD-L1 tumor proportion score (TPS) of ≥ 50%, 1-49%, < 1%, and unknown were 28%, 27%, 28%, and 17%, respectively. At data cutoff on August 31, 2019, median patient follow-up was 20.3 months (range 12-28 months), and median real-world times on treatment (rwToT) with pembrolizumab and pemetrexed were 5.6 (95% CI 4.5-6.4) and 2.8 months (95% CI 2.2-3.5), respectively. Median overall survival (OS) was 16.5 months (95% CI 13.2-20.6); estimated 12-month survival was 59.5% (95% CI 53.3-65.0); rwProgression-free survival was 6.4 months (95% CI 5.4-7.8); and rwTumor response rate (complete or partial response) was 56.5% (95% CI 50.5-62.4). Median OS was 20.6, 16.3, 13.2, and 13.7 months for patient cohorts with PD-L1 TPS ≥ 50%, 1-49%, < 1%, and unknown, respectively. These findings demonstrate the effectiveness of pembrolizumab plus pemetrexed-carboplatin by describing clinical outcomes among patients with metastatic nonsquamous NSCLC who were treated at US oncology practices.
| S-EPMC8080779 | biostudies-literature
Project description:IntroductionOver the past decade, ALK tyrosine kinase inhibitors have delivered unprecedented survival for individuals with ALK-positive (ALK+) lung cancers. Real-world data enhance the understanding of optimal drug sequencing and expectations for survival.MethodsMulticenter real-world study of individuals with pretreated advanced ALK+ lung cancers managed on a lorlatinib access program between 2016 and 2020. Key outcomes were lorlatinib efficacy, tolerability, and treatment sequencing. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method among all individuals (PFSa and OSa), with at least 30 days (one-cycle) lorlatinib exposure (PFSb and OSb), and with good performance status (PFSc and OSc). Subgroups of interest were analyzed to assess signals of potential clinical applicability. Two OS index dates were analyzed, from lorlatinib initiation and advanced ALK+ diagnosis.ResultsThe population (N = 38, 10 sites) was heavily pretreated (23 had ≥2 previous treatment lines) with a high disease burden (26 had 2-4 sites and 11 had >4 sites of metastatic disease, 19 had brain metastases). The overall response rate was 44% and the disease control rate was 81%. Lorlatinib dose reduction (18%), interruption (16%), and discontinuation (3%) were consistent with the trial experience. From advanced ALK+ diagnosis, the median OS for populations a, b, and c was 45.0 months, 69.9 months and 61.2 months respectively. From lorlatinib initiation, the median PFSa, PFSb and PFSc was 7.3 months, 13.2 months and 27.7 months and the median OSa, OSb and OSc was 19.9 months, 25.1 months and 27.7 months. The median PFSa with versus without brain metastases was 34.6 months versus 5.8 months (p = 0.09). The intracranial median PFS was 14.2 months. Previous good response versus poor response to the first ALK-directed therapy median PFSa was 27.7 months versus 4.7 months with a hazard ratio of 0.3 (p = 0.01).ConclusionsLorlatinib is a potent, highly active brain-penetrant third-generation ALK tyrosine kinase inhibitors with benefits for most individuals in the later-line setting in a real-world evaluation, consistent with clinical trial data.
| S-EPMC10106481 | biostudies-literature