Efficacy of Immune Checkpoint Inhibitors for Lung Cancer According to Patient Age and Eastern Cooperative Oncology Group Performance Status: A Systematic Review and Meta-analysis

Abstract Background For treatment of advanced lung cancer, immune checkpoint inhibitors (ICIs) + chemotherapy or the combination of dual ICIs has become the standard first-line treatment in recent years. Considering the differences among patients’ immune systems, the response to ICIs may vary. Therefore, we aimed to evaluate the predictive implications of patient age and Eastern Cooperative Oncology Group (ECOG) performance status (PS) for the efficacy of ICIs for the treatment of lung cancer. Methods We searched the PubMed, Cochrane Library, Web of Science, and EMBASE databases for articles published between January 2010 and September 2020 that compared overall (OS) and progression-free survival (PFS) rates between patients with lung carcinoma who were administered ICIs and control treatments. Results Twenty-four trials including 15,584 patients were selected. ICIs significantly improved the OS rates in patients aged < 65 (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.65–0.82) and ≥ 65 (0.75 [0.70–0.82]) years, with an age cut-off of 65 years; patients aged < 65 (0.83 [0.72–0.95]) years, when age was classified as < 65, 65–74, and ≥ 75 years; and patients with an ECOG PS score of 0 (0.77 [0.69–0.86]) and 1 (0.78 [0.72–0.85]). However, the differences between the two age groups (p = 0.69), the three age groups (p = 0.43), and the ECOG PS groups (p = 0.82) were not insignificant. Significant advantages of ICIs in terms of PFS rates were found in patients aged < 65 (0.64 [0.52–0.79]) and ≥ 65 (0.73 [0.64–0.84]) years and in those with an ECOG PS score of 0 (0.63 [0.49–0.82]) and 1 (0.66 [0.59–0.75]). No significant difference was observed between the age (p = 0.35) and ECOG PS groups (p = 0.89). Conclusions Younger patients benefited more from ICI administration; however, lung cancer treatment cannot be decided based on age. Patients with different ECOG PS could benefit from ICIs, but data on patients with an ECOG PS score of ≥ 2 are lacking. In future studies, more patients with poor ECOG PS scores should be included.

Download Full-text

The efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer patients of different age groups: a meta-analysis

Clinical & Translational Oncology ◽

10.1007/s12094-019-02241-5 ◽

2019 ◽

Vol 22 (7) ◽

pp. 1146-1154

Author(s):

S.-Y. Zheng ◽

H.-J. Cui ◽

H. Duan ◽

Y.-M. Peng ◽

Q. Li ◽

...

Keyword(s):

Lung Cancer ◽

Clinical Trials ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Age Groups ◽

Small Cell ◽

Small Cell Lung ◽

Nsclc Patients

Abstract Background Age is closely related to the efficacy of treatment for non-small cell lung cancer (NSCLC) patients. Latest clinical trials have proved the better overall survival (OS) for the use of immune checkpoint inhibitors verse chemotherapy in NSCLC patients. However, we had no clear idea of the efficacy of them in elderly patients. So we conducted a meta-analysis to compare the efficacy of immune checkpoint inhibitors for NSCLC patients of different age groups and summarized overall treatment-related adverse events. Materials and methods PubMed, EMBASE, Web of Science and the Cochrane Library were searched for all clinical trials in NSCLC until 30th of April 2019. Eligible studies included randomized controlled trials (RCTs) comparing immune checkpoint inhibitors with chemotherapy in NSCLC patients. The hazard ratio (HRs) and 95% confidence intervals (CIs) of OS, progression-free survival or adverse events (AEs) were used. Results A total of 4994 patients from 8 RCTs were included. Immune checkpoint inhibitors significantly prolonged the OS (HR, 0.73; 95% CI, 0.61–0.89) versus chemotherapy in NSCLC patients who were less than 65 years old. Also, they prolonged the OS (HR, 0.74; 95% CI, 0.59–0.93) in NSCLC patients who were more than 65 years old. However, there was no statistical significance of OS (HR, 0.87; 95% CI, 0.57–1.30) among NSCLC patients who were more than 75 years old. It also showed that the single use of immune checkpoint inhibitors had fewer all-grade AEs. Conclusion Regardless of the NSCLC patients who were less or more than 65 years, immune checkpoint inhibitors could achieve better OS than chemotherapy. But there was no significant difference when NSCLC patients who were more than 75 years old. Older patient should be offered immune therapies if it is possible and the mechanism in old age treatment should be further studied.

Download Full-text

Immune checkpoint inhibitor efficacy and safety in older non-small cell lung cancer patients

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyaa152 ◽

2020 ◽

Vol 50 (12) ◽

pp. 1447-1453

Author(s):

Toshio Kubo ◽

Hiromi Watanabe ◽

Kiichiro Ninomiya ◽

Kenichiro Kudo ◽

Daisuke Minami ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Performance Status ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancer Patients

Abstract Objectives Immune checkpoint inhibitors offer longer survival than chemotherapy in several clinical trials for advanced non-small cell lung cancer. In subset analyses of clinical trials, immune checkpoint inhibitors extended survival in patients aged ≥65 years, but the effects in patients aged ≥75 years are controversial. We performed multicenter, collaborative and retrospective analyses of immune checkpoint inhibitor efficacy and safety in non-small cell lung cancer patients aged ≥75 years. Methods We retrospectively studied 434 advanced non-small cell lung cancer patients who received immune checkpoint inhibitors from December 2015 to December 2017, and retrospectively applied the Geriatric (G) 8 screening tool with medical records. Results Of the 434 patients who received immune checkpoint inhibitors, 100 were aged ≥75 years. Five patients with performance status 3 were omitted from the final analysis. Immune checkpoint inhibitors were given as a first-line treatment to 20 patients. The objective response rates, median progression-free survival rates and median survival times were 35.0%, 6.1 months and 10.7 months for first-line treatment, and 20.0%, 2.9 months and 14.7 months for second- or later-line treatments, respectively. The median modified G8 score was 11.0. The median survival time was longer in the high modified G8 (≥12.0) group than in the low modified G8 (≤11.0) group (18.7 vs. 8.7 months; P = 0.02). Likewise, the median survival time was 15.5 months (performance status 0–1) vs. 3.2 months (performance status 2) (P < 0.01). The grade ≥ 2 immune-related adverse events incidence was 36.8%. Conclusions In this study, immune checkpoint inhibitors were effective and tolerable for patients aged ≥75 years. The modified G8 screening tool and performance status were associated with the outcome of older non-small cell lung cancer patients treated with immune checkpoint inhibitors.

Download Full-text

The Role of Performance Status in Small-Cell Lung Cancer in the Era of Immune Checkpoint Inhibitors

Clinical Lung Cancer ◽

10.1016/j.cllc.2020.04.006 ◽

2020 ◽

Vol 21 (6) ◽

pp. e539-e543 ◽

Cited By ~ 2

Author(s):

Alex Friedlaender ◽

Stephen V. Liu ◽

Antonio Passaro ◽

Giulio Metro ◽

Giuseppe Banna ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Performance Status ◽

Small Cell ◽

Small Cell Lung

Download Full-text

Clinical Effectiveness of Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer with a Poor Performance Status

Medicina ◽

10.3390/medicina57111273 ◽

2021 ◽

Vol 57 (11) ◽

pp. 1273

Author(s):

Kyoichi Kaira ◽

Hisao Imai ◽

Atsuto Mouri ◽

Ou Yamaguchi ◽

Hiroshi Kagamu

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Performance Status ◽

Poor Performance ◽

Poor Performance Status ◽

First Line ◽

Lung Cancer Patients

Immune checkpoint inhibitors (ICIs) are standard treatments for patients with lung cancer. PD-1/PD-L1 or CTLA4 antibodies are chosen as the first-line therapy, contributing to the long-term survival and tolerability. Unlike molecular targeting agents, such as gefitinib, lung cancer patients with a poor performance status (PS) display unsatisfactory clinical improvements after ICI treatment. Several previous reports also demonstrated that the PS is identified as one of the most probable prognostic factors for predicting poor outcomes after ICI treatment. However, first-line pembrolizumab seemed to be effective for lung cancer patients with a PS of 2 if PD-L1 expression was greater than 50%. Currently, the induction of ICIs in patients with lung cancer with a poor PS is controversial. These problems are discussed in this review.

Download Full-text

P2.04-28 Use of Immune Checkpoint Inhibitors (ICIs) in Patients with Refractory Non-Small Cell Lung Cancer (NSCLC) and Poor Performance Status (PS)

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2018.08.1252 ◽

2018 ◽

Vol 13 (10) ◽

pp. S741 ◽

Cited By ~ 1

Author(s):

J. Thompson ◽

C. Arce-Lara ◽

S. Menon

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Performance Status ◽

Poor Performance ◽

Small Cell ◽

Poor Performance Status ◽

Small Cell Lung

Download Full-text

Performance status and end‐of‐life care among adults with non–small cell lung cancer receiving immune checkpoint inhibitors

Cancer ◽

10.1002/cncr.32782 ◽

2020 ◽

Vol 126 (10) ◽

pp. 2288-2295 ◽

Cited By ~ 6

Author(s):

Laura A. Petrillo ◽

Areej El‐Jawahri ◽

Ryan D. Nipp ◽

Morgan R. L. Lichtenstein ◽

Sienna M. Durbin ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Immune Checkpoint ◽

End Of Life Care ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Performance Status ◽

Small Cell ◽

Life Care ◽

Small Cell Lung

Download Full-text

Inferring the role of the microbiome on survival in patients treated with immune checkpoint inhibitors: causal modeling, timing, and classes of concomitant medications

10.1101/19006429 ◽

2019 ◽

Author(s):

Daniel Spakowicz ◽

Rebecca Hoyd ◽

Mitchell Muniak ◽

Marium Husain ◽

James S. Bassett ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Group Performance ◽

Checkpoint Inhibitors ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Histamine Receptor ◽

Causal Modeling ◽

Charlson Comorbidity Index Score ◽

Medication Effects

ABSTRACTThe microbiome has been shown to affect the response to Immune Checkpoint Inhibitors (ICIs) in a small number of cancers. Here, we sought to more broadly survey cancers to identify those in which the microbiome will play a role using retrospective analyses. We created a causal model for the relationship between medications, the microbiome and ICI response and used it to guide the abstraction of electronic health records of 690 patients who received ICI therapy for advanced cancer. Medications associated with changes to the microbiome including antibiotics, corticosteroids, proton pump inhibitors, histamine receptor blockers, non-steroid anti-inflammatories and statins were abstracted. We tested the effect of medication timing on overall survival (OS) and evaluated the robustness of medication effects in each cancer. Finally, we compared the size of the effect observed for antibiotics classes to taxa correlated with ICI response and a literature review of culture-based antibiotic susceptibilities. Of the medications assessed, only antibiotics and corticosteroids significantly associated with lower OS. The hazard ratios (HRs) for antibiotics and corticosteroids were highest near the start of ICI treatment but remained significant when given prior to ICI. Antibiotics and corticosteroids remained significantly associated with OS even when controlling for multiple factors such as Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index score, and stage. When grouping antibiotics by class, β-lactams showed the strongest association with OS across all tested cancers. The timing and strength of these effects after controlling for confounding factors are consistent with role for the microbiome in response to ICIs.

Download Full-text