Dataset Information

Clinical outcomes of hyperprogression based on volumetry in non-small cell lung cancer after immune checkpoint inhibitor treatment.

ABSTRACT:

Background

Hyperprogressive disease (HPD) is a novel pattern of the treatment course after immune checkpoint inhibitor (ICI) therapy in patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics, outcomes, and associated factors of HPD using a semiautomatic volume measurement.

Methods

This retrospective study enrolled patients with recurrent and/or metastatic NSCLC treated with ICIs between January 2015 and August 2019 at eight tertiary centers in Korea. HPD was defined according to the tumor growth kinetics and time to treatment failure. Tumor volume was measured using a semiautomatic software.

Results

A total of 219 NSCLC patients with 35 HPD by volumetric measurement (HPDv) (15.9%) were enrolled. The median duration of overall survival (OS) and OS after ICI treatment (ICI-OS) were 34.5 and 18.4 months, respectively. HPDv patients had significantly worse progression-free survival (PFS) than progressive disease patients without HPDv (1.16 vs. 1.82 months, p-value <0.001). ICI-OS did not significantly differ between patients with HPDv and those without HPDv (2.66 vs. 5.4 months, p = 0.105). PD-L1 expression lower than 50%, more than three metastatic sites, neutrophil-to-lymphocyte ratio equal to or higher than 3.3, and hemoglobin level lower than 10 were found to be associated with HPDv.

Conclusions

There is no standardized definition of HPD. However, defining HPD in NSCLC patients treated with ICI using a semiautomatic volume measurement software is feasible.

SUBMITTER: Kim J

PROVIDER: S-EPMC9346184 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Clinical outcomes of hyperprogression based on volumetry in non-small cell lung cancer after immune checkpoint inhibitor treatment.

Kim Jehun J Kim Taeyun T Jang Tae Won TW Kang Hee H Kim Mi Hyun MH Yoon Seong Hoon SH Son Choon-Hee CH Lee Hyun-Kyung HK Kim Hyun-Kuk HK Lee Shin Yup SY Shin Kyeong Choel KC Han Ji-Yeon JY Kang Eun-Ju EJ

Thoracic cancer 20220703 15

<h4>Background</h4>Hyperprogressive disease (HPD) is a novel pattern of the treatment course after immune checkpoint inhibitor (ICI) therapy in patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics, outcomes, and associated factors of HPD using a semiautomatic volume measurement.<h4>Methods</h4>This retrospective study enrolled patients with recurrent and/or metastatic NSCLC treated with ICIs between January 2015 and August 2019 at eight t ...[more]

PMID: 35785522

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Project description:ImportanceDerived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level have been correlated with immune checkpoint inhibitor (ICI) outcomes in patients with melanoma.ObjectiveTo determine whether pretreatment dNLR and LDH are associated with resistance to ICIs in patients with advanced non-small cell lung cancer (NSCLC).Design, setting, and participantsMulticenter retrospective study with a test (n = 161) and a validation set (n = 305) treated with programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors in 8 European centers, and a control cohort (n = 162) treated with chemotherapy only. Complete blood cell counts, LDH, and albumin levels were measured before ICI treatment. A lung immune prognostic index (LIPI) based on dNLR greater than 3 and LDH greater than upper limit of normal (ULN) was developed, characterizing 3 groups (good, 0 factors; intermediate, 1 factor; poor, 2 factors).Main outcomes and measuresThe primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS) and disease control rate (DCR).ResultsIn the pooled ICI cohort (N = 466), 301 patients (65%) were male, 422 (90%) were current or former smokers, and 401 (87%) had performance status of 1 or less; median age at diagnosis was 62 (range, 29-86) years; 270 (58%) had adenocarcinoma and 159 (34%) had squamous histologic subtype. Among 129 patients with PD-L1 data, 96 (74%) had PD-L1 of at least 1% by immunohistochemical analysis, and 33 (26%) had negative results. In the test cohort, median PFS and OS were 3 (95% CI, 2-4) and 10 (95% CI, 8-13) months, respectively. A dNLR greater than 3 and LDH greater than ULN were independently associated with OS (hazard ratio [HR] 2.22; 95% CI, 1.23-4.01 and HR, 2.51; 95% CI, 1.32-4.76, respectively). Median OS for poor, intermediate, and good LIPI was 3 months (95% CI, 1 month to not reached [NR]), 10 months (95% CI, 8 months to NR), and 34 months (95% CI, 17 months to NR), respectively, and median PFS was 2.0 (95% CI, 1.7-4.0), 3.7 (95% CI, 3.0-4.8), and 6.3 (95% CI, 5.0-8.0) months (both P < .001). Disease control rate was also correlated with dNLR greater than 3 and LDH greater than ULN. Results were reproducible in the ICI validation cohort for OS, PFS, and DCR, but were nonsignificant in the chemotherapy cohort.Conclusions and relevancePretreatment LIPI, combining dNLR greater than 3 and LDH greater than ULN, was correlated with worse outcomes for ICI, but not for chemotherapy, suggesting that LIPI can serve as a potentially useful tool when selecting ICI treatment, raising the hypothesis that the LIPI might be useful for identifying patients unlikely to benefit from treatment with an ICI.

Project description:PurposeLung cancer is one of the most common types of cancer, resulting in approximately 1.8 million deaths worldwide. Immunotherapy using checkpoint inhibitors has become standard of care in advanced non-small cell lung cancer (NSCLC), and there is increasing interest in further improving outcomes through combination with other therapeutics. This systematic review evaluates emerging phase III data on the efficacy and safety of checkpoint inhibitor combinations as first-line treatment for advanced NSCLC.Materials and methodsPublished and presented literature was searched using the key search terms "non-small cell lung cancer" AND "checkpoint-inhibitors" (OR respective aliases) AND phase III trials. Seven randomized phase III clinical trials reporting outcomes on checkpoint inhibitor combinations in first-line advanced NSCLC were identified.ResultsFour first-line trials reported outcomes for checkpoint inhibitor combinations in nonsquamous NSCLC. Pembrolizumab-chemotherapy, atezolizumab-chemotherapy, and atezolizumab-bevacizumab-chemotherapy showed significantly improved overall survival compared with controls in patients with advanced nonsquamous epidermal growth factor receptor-negative (EGFR-)/ anaplastic lymphoma kinase gene (ALK)- NSCLC. Two trials reported outcomes for squamous NSCLC, with pembrolizumab-chemotherapy reporting significantly improved overall survival (OS) compared with chemotherapy. The combination of nivolumab-ipilimumab in all-comer histology failed to improve OS compared with histology appropriate chemotherapy in patients regardless of their tumor mutational burden status. Based on improved survival and safety, either pembrolizumab monotherapy or pembrolizumab-chemotherapy administered based on PD-L1 status and histology is a preferred treatment option. Outcomes for atezolizumab-bevacizumab-chemotherapy in EGFR+/ALK+ patients are promising and require further exploration.ConclusionFirst-line checkpoint inhibitors added to standard therapies improve overall survival for nonsquamous EGFR-/ALK- and squamous advanced NSCLC.Implications for practiceSingle-agent immune checkpoint inhibitors are now standard of care for advanced non-small cell lung cancer (NSCLC), and emerging data show that combining these agents with established chemotherapy further improves outcomes. The phase III KEYNOTE-189 and IMPower-130 trials showed significantly improved survival using this strategy for nonsquamous NSCLC, and the phase III KEYNOTE-407 trial showed similar results in squamous disease. Checkpoint inhibitor combinations are therefore an important new treatment option for first-line NSCLC. Programmed death ligand-1 expression may inform the use of checkpoint inhibitor combination therapy, and overall tumor mutation burden is also an emerging biomarker for this new treatment strategy.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have led to dramatic improvements in survival a subset of patients with non-small cell lung cancer (NSCLC); however, they have been shown to cause life-threatening toxicity such as immune checkpoint inhibitor-related pneumonitis (CIP). Our previous studies have shown that chronic obstructive pulmonary disease (COPD) and circulating cytokines are associated with clinical outcomes in NSCLC patients receiving ICIs. However, the relationship between these factors and the development of CIP is unclear. In this study, we retrospectively assessed NSCLC patients receiving ICIs to identify CIP risk factors.MethodsThis retrospective cohort study reviewed medical records of NSCLC patients receiving ICIs targeting programmed cell death 1 (PD-1) or its ligand PD-L1 between March 2017 and December 2020 at Zhongshan Hospital Fudan University. CIP was diagnosed by the treating investigator. Clinical characteristics and baseline plasma cytokines were collected. Logistic regression was used to compare clinical characteristics and circulating cytokine levels between patients with and without CIP to identify CIP risk factors.ResultsOf 164 NSCLC patients who received ICIs, CIP developed in 20 cases (12.2%). The presence of COPD [odds ratio (OR), 7.194; 95% confidence interval (CI): 1.130 to 45.798; P=0.037] and PD-L1 expression of ≥50% (OR, 7.184; 95% CI: 1.154 to 44.721; P=0.035) were independently associated with a higher incidence of CIP, whereas a higher baseline level of interleukin-8 (IL-8) was associated with a lower incidence of CIP (OR, 0.758; 95% CI: 0.587 to 0.978; P=0.033). The independent risk factors from final multivariate analysis were incorporated into a nomogram to predict the incidence of CIP. The nomogram model receiver operating characteristic (ROC) curve had a good predictive accuracy of 0.883 (95% CI: 0.806 to 0.959).ConclusionsIncreased risk of CIP independently associated with history of COPD, tumor PD-L1 expression ≥50%, and low baseline IL-8 level. The nomogram may hold promise for CIP risk assessment in the administration of ICIs.

Dataset Information

Clinical outcomes of hyperprogression based on volumetry in non-small cell lung cancer after immune checkpoint inhibitor treatment.

Background

Methods

Results

Conclusions

Publications

Clinical outcomes of hyperprogression based on volumetry in non-small cell lung cancer after immune checkpoint inhibitor treatment.

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