Association of Performance Status With Survival in Patients With Advanced Non–Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy

Sehgal, Kartik; Gill, Ritu R.; Widick, Page; Bindal, Poorva; McDonald, Danielle C.; Shea, Meghan; Rangachari, Deepa; Costa, Daniel B.

doi:10.1001/jamanetworkopen.2020.37120

Cited by 90 publications

(82 citation statements)

References 21 publications

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“…This result is consistent with previously published studies [10][11][12][13]. Worse performance status was associated with decreased efficacy of ICIs considering PFS and OS; this result is similar to previous observations [5,7] and consistent with clinical trials [22][23][24].…”

Section: Discussionsupporting

confidence: 93%

Interrelations between Patients’ Clinicopathological Characteristics and Their Association with Response to Immunotherapy in a Real-World Cohort of NSCLC Patients

Callejo

Frigola²,

Iranzo

et al. 2021

Cancers

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Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment. Unfortunately, only some patients benefit from these therapies. Thus, certain clinicopathological characteristics of the patients have been proposed as biomarkers of ICIs response. We assembled a retrospective cohort of 262 NSCLC patients treated with ICIs, compiled relevant clinicopathological characteristics, and studied their associations with treatment outcome using Cox proportional-hazards survival models. Additionally, we investigated the interrelations between clinicopathological features and devised a method to create a compendium associated with ICIs response by selecting those that provide non-redundant information. In multivariate analyses, ECOG performance status (hazard ratio (HR) 1.37 (95% CI 1.11 to 1.68), p < 0.005), LDH (HR 1.24 (95% CI 1.03 to 1.48), p = 0.02)) and PD-L1 negativity were associated with decreased PFS (HR 1.92 (95% CI 1.03 to 3.58), p < 0.04), whereas presentation of immune-related adverse events (irAEs) (HR 0.35 (95% CI 0.22 to 0.55, p < 0.005) or females (HR 0.52 (95% CI 0.33 to 0.80, p < 0.005) had longer progression-free survival. Additionally, numerous clinicopathological indicators were found to be interrelated. Thus, we searched for features that provide non-redundant information, and found the combination of LDH levels, irAEs, and gender to have a better association with ICIs treatment response (cross-validated c-index = 0.66). We concluded that several clinicopathological features showed prognostic value in our real-world cohort. However, some are interrelated, and compendiums of features should therefore consider these interactions. Joint assessment of LDH, irAEs, and gender may be a good prognostic compendium.

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Section: Discussionsupporting

confidence: 93%

Interrelations between Patients’ Clinicopathological Characteristics and Their Association with Response to Immunotherapy in a Real-World Cohort of NSCLC Patients

Callejo

Frigola²,

Iranzo

et al. 2021

Cancers

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“…Although conventional chemotherapy is not recommended for lung cancer patients with poor PS, modern anti-cancer treatments, including immunotherapies and targeted therapies, are relatively convenient and less toxic than chemotherapy. Although those treatments had been 23,24 After multivariate analysis, our study showed that PS remained an important prognostic factor for PFS and OS among older patients treated with EGFR-TKIs. More metastatic sites indicate a higher tumor burden and may reflect the aggressiveness and rapid growth of cancer cells, which might be associated with a poor prognosis.…”

Section: Discussionmentioning

confidence: 78%

Efficacy and Prognosis of First-Line EGFR-Tyrosine Kinase Inhibitor Treatment in Older Adults Including Poor Performance Status Patients with EGFR-Mutated Non-Small-Cell Lung Cancer

Chang¹,

Chang²,

Lai³

et al. 2021

CMAR

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Introduction: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutated non-small-cell lung cancer (NSCLC) patients. The efficacy of EGFR-TKIs in older patients including poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) is seldom investigated. Methods: We enrolled patients 65 years or older with EGFR-mutated Stage IIIB-IV NSCLC and evaluated the efficacy and prognosis of first-line EGFR-TKI treatment. Clinical and demographic characteristics were reviewed and analyzed, including age, sex, PS, smoking history, EGFR mutation type, treatment regimen, progression-free survival (PFS), and overall survival (OS). Results: From January 2015 to December 2019, a total of 237 patients were included, 205 of whom were eligible for efficacy and outcome analyses. Among them, 91 (44.4%) were categorized as poor PS (2-4). Compared with patients categorized as good PS (0-1), those with poor PS were older (79 versus 75 years), had a higher proportion of brain metastases (41.8% versus 25.4%), more comorbidities (74.7% versus 54.4%), and more likely to be treated with first-generation TKIs (74.7% versus 57.0%). The PFS and OS were 17.1 and 26.7 months respectively in patients with good PS and 12.7 and 18.2 months in those with poor PS (both p < 0.001). In the multivariate analysis, good PS, <3 metastatic sites, and firstline treatment with afatinib compared with erlotinib and gefitinib were associated with longer PFS. A relatively younger age, good PS, < 3 metastatic sites, and no brain metastasis at diagnosis were associated with better OS. Conclusion:In older patients with EGFR-mutated NSCLC and receive EGFR-TKI treatment, a good PS and <3 metastatic sites at diagnosis were associated with a longer PFS and OS. In addition, afatinib as first-line treatment was associated with a longer PFS whereas a relatively younger age and no brain metastasis at diagnosis were associated with better OS.

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“…In our study, no patients had a complete response and the partial response rate (PRR) in the overall population was slightly lower than in the KEYNOTE-024; we also found a significant decrease in PRR in patients with a PS ≥ 2. In other studies, the objective response rate (partial plus complete response) in PS ≥ 2 patients ranged between 17.9% and 45% [ 12 , 20 , 21 , 22 , 23 ]. In contrast with our results, most authors have not found significant differences according to PS [ 12 , 20 , 23 ], with the exception of Alessi et al [ 22 ], who detected a significantly poorer objective response rate in patients with a PS of 2 (43.1 vs. 25.6%), although this variable in our cohort with a PS ≥ 2 was notably lower.…”

Section: Discussionmentioning

confidence: 93%

“…The retrospective study carried out by Sehgal et al [ 20 ] included 74 patients with advanced NSCL treated in monotherapy with pembrolizumab. The purpose of this study was to determine the influence of PS on PFS and OS.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, in our cohort, there were no statistically significant differences between these two subgroups of patients. In the study conducted by Alessi et al [ 20 ], a low proportion of PS = 2 patients were included (16.7%), but also median PFS and OS were shorter in patients with PS = 2 (4 and 7.4 months, respectively). In this study, baseline characteristics were balanced according to PS.…”

Section: Discussionmentioning

confidence: 99%

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Influence of Performance Status on the Effectiveness of Pembrolizumab Monotherapy in First-Line for Advanced Non-Small-Cell Lung Cancer: Results in a Real-World Population

Galán

Mel

Pérez-Moreno

et al. 2021

Biology

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The KEYNOTE-024 clinical trial showed promising results for pembrolizumab in the first-line of treatment of advanced non-small-cell lung cancer (NSCLC). However, the profile of patients in real-world practice differs from those included in this clinical trial. Here, an observational single-center retrospective study was performed through a comparative analysis of clinical outcomes after pembrolizumab therapy according to the Eastern Cooperative Oncology Group Stage Performance Status (ECOG PS). Moreover, univariate and multivariate analyses were carried out to detect prognostic factors. In our cohort, 63.7% of patients had an ECOG PS of 0–1. Regarding response rate, 31.8% of patients had a partial response (PR), 19.3% had stable disease (SD) and 23.9% had progression disease. On the other hand, patients with ECOG PS ≥ 2 showed a significantly lower rate of PR and SD to pembrolizumab than patients with a PS of 0–1. The rate of response, median overall survival (OS) and progression-free survival (PFS) were significantly higher in patients with ECOG PS 0–1 than in those with ECOG PS ≥ 2. In the current study, we found ECOG PS as the only independent predictor of OS and PFS. Due to the ECOG PS scale being a subjective parameter, other tools are needed to identify treatment effectiveness to each patient.

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Association of Performance Status With Survival in Patients With Advanced Non–Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy

Cited by 90 publications

References 21 publications

Interrelations between Patients’ Clinicopathological Characteristics and Their Association with Response to Immunotherapy in a Real-World Cohort of NSCLC Patients

Interrelations between Patients’ Clinicopathological Characteristics and Their Association with Response to Immunotherapy in a Real-World Cohort of NSCLC Patients

Efficacy and Prognosis of First-Line EGFR-Tyrosine Kinase Inhibitor Treatment in Older Adults Including Poor Performance Status Patients with EGFR-Mutated Non-Small-Cell Lung Cancer

Influence of Performance Status on the Effectiveness of Pembrolizumab Monotherapy in First-Line for Advanced Non-Small-Cell Lung Cancer: Results in a Real-World Population

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