Checkpoint Inhibitors for Non-Small Cell Lung Cancer Among Older Adults

Elias, Rawad; Morales, Joshua; Presley, Carolyn J.

doi:10.1007/s11912-017-0619-0

Cited by 21 publications

(20 citation statements)

References 109 publications

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“…No differences were observed in terms of PFS, OS and frequency of irAEs when compared with a cohort of younger patients (≤74 years old) who received a parallel treatment in the same time period. These data are in line with the results of previous studies reporting the efficacy and the safety of anti-PD-1 and anti-PD-L1 mABs in elderly patients [20][21][22][23]. The majority of these studies, however, chose a cut-off of 65 years according to the international guidelines and may not clearly reflect the actual elderly population affected by lung cancer.…”

Section: Discussionsupporting

confidence: 87%

Distinctive Role of the Systemic Inflammatory Profile in Non-Small-Cell Lung Cancer Younger and Elderly Patients Treated with a PD-1 Immune Checkpoint Blockade: A Real-World Retrospective Multi-Institutional Analysis

Nardone

Giannicola

Giannarelli

et al. 2021

Life

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An immune checkpoint blockade with mAbs to PD-1 and PD-L1 is an expanding therapeutic option for mNSCLC patients. This treatment strategy is based on the use of mAbs able to restore the anti-tumor activity of intratumoral T cells inhibited by PD-1 binding to PD-L1/2 on tumor and inflammatory cells. It has been speculated that a chronic status of systemic inflammation as well as the immunosenescence physiologically occurring in elderly patients may affect the efficacy of the treatment and the occurrence of irAEs. We performed a multi-institutional retrospective study aimed at evaluating the effects of these mAbs (nivolumab or atezolizumab) in 117 mNSCLC patients younger (90 cases) and older (27 cases) than 75 years in correlation with multiple inflammatory parameters (NLR, CRP, ESR, LDH and PCT). No differences were observed when the cohorts were compared in terms of the frequency of PFS, OS, inflammatory markers and immune-related adverse events (irAEs). Similarly, the occurrence of irAEs was strictly correlated with a prolonged OS survival in both groups. On the contrary, a negative correlation between the high baseline levels of inflammatory markers and OS could be demonstrated in the younger cohort only. Overall, PD-1/PD-L1-blocking mAbs were equally effective in young and elderly mNSCLC patients; however, the detrimental influence of a systemic inflammation at the baseline was only observed in young patients, suggesting different aging-related inflammation immunoregulative effects.

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Section: Discussionsupporting

confidence: 87%

Distinctive Role of the Systemic Inflammatory Profile in Non-Small-Cell Lung Cancer Younger and Elderly Patients Treated with a PD-1 Immune Checkpoint Blockade: A Real-World Retrospective Multi-Institutional Analysis

Nardone

Giannicola

Giannarelli

et al. 2021

Life

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“…Studies of cancers diagnosed and deaths by age-group show that elderly patients (≥65 years) are overrepresented with a further increase expected over the next decade, eg, data with NSCLC. 72 Yet this population is quite underrepresented in clinical trials, and it has been known for many years that aging per se is reflected in many changes in immunity, both qualitative and quantitative. 73 , 74 As more attention is paid to this discrepancy, we can anticipate an improved understanding of checkpoint blockade in aging, more specific clinical trials for elderly cancer patients, and an improved “juggling” of combination immunotherapies to improve cancer survival across multiple disease types.…”

Section: Discussionmentioning

confidence: 99%

Checkpoint blockade in solid tumors and B-cell malignancies, with special consideration of the role of CD200

Gorczynski¹,

Zhu²

2017

CMAR

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In the ontogeny of a normal immune response, a series of checkpoints must be overcome to ensure that unwanted and/or harmful self-directed activation responses are avoided. Many of the molecules now known to be active in this overseeing of the evolving immune activation cascade, contributing inhibitory signals to dampen an overexuberant response, belong to the immunoglobulin supergene family. These include members of the CD28/CTLA-4:B7.1/B7.2 receptor/ligand family, PD-1 and PDL-1, CD200 and CD200R, and the more recently described V-domain immunoglobulin suppressor of T-cell activation and its ligand (VSIG-3/IGSF11). Unfortunately, from the point of view of improving immunotargeting of cancer cells, triggering these checkpoint inhibitory signaling pathways, so necessary to maintain self-tolerance, simultaneously acts to prevent effective tumor immunity. The recent development of reagents, predominantly antibodies, to act as checkpoint blockade agents, has had a dramatic effect on human cancer treatment, with a marked reported success for anti-CTLA-4 and PD-1 in particular in clinical trials. This review provides a general overview of the data now available showing the promise of such treatments to our cancer armamentarium and elaborates in depth on the potential promise of what can be regarded as an underappreciated target molecule for checkpoint blockade in chronic lymphocytic leukemia and solid tumors, CD200.

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“…It is important to explore the survival benefit of immunotherapy in elderly patients because an increase in age is usually accompanied with a decline in functions of the immune system, especially the T cell-mediated immune defense system, resulting in a poor efficacy of immune checkpoint inhibitors for the treatment of elderly patients (21). Other studies have shown that aging may not affect the effectiveness of immunotherapy (22)(23)(24). In the current study, we included nine NSCLC patients aged over 70 years old and found that two of them reached a PR and five reached SD, indicating that there was no significant difference in the benefit of such a treatment in older patients compared with younger patients.…”

Section: Discussionmentioning

confidence: 99%

Clinical Efficacy of Immunotherapy with Pd-1/Pd-L1 Inhibitors for the Treatment of Advanced Non-Small Cell Lung Cancer

Yang¹,

Ma²,

Zhang³

et al. 2020

2020 International Clinical &Amp; Experimental Pharmacology and Oncology Forum (ICEPOF 2020)

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Immunotherapeutics like programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors effectively control non-small cell lung cancer (NSCLC) in clinical trials. This study assessed the association of different clinicopathological parameters with the treatment effectiveness and prognosis of NSCLC patients in a real-world setting. Seventy-five patients received PD-1/PD-L1 inhibitors and were evaluated for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Eighteen patients reached a partial response (PR) (24%), 45 had stable disease (SD) (60%), and 12 had progressive disease (PD) (16%), resulting in an ORR of 24% and a DCR of 84%. For the 11 PD-L1-positive patients, the ORR was 36.36%. Moreover, 16 patients (21%) had died and 34 (45%) had SD at the last follow-up, leading to a PFS of 8.3 months (95% confidence interval (CI): 6.8-12.2 months) and an OS of 17 months (95%CI: 16.7-26.5 months). The Eastern Cooperative Oncology Group (ECOG) score was associated with the treatment-related PFS and OS. The factors associated with the prognosis were ECOG score, line of immunotherapy, tobacco smoking, PD-L1 positivity, and tumor pathology. This study confirmed the clinical effectiveness of PD-1/PD-L1 inhibitor immunotherapy against advanced NSCLC.

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Checkpoint Inhibitors for Non-Small Cell Lung Cancer Among Older Adults

Cited by 21 publications

References 109 publications

Distinctive Role of the Systemic Inflammatory Profile in Non-Small-Cell Lung Cancer Younger and Elderly Patients Treated with a PD-1 Immune Checkpoint Blockade: A Real-World Retrospective Multi-Institutional Analysis

Distinctive Role of the Systemic Inflammatory Profile in Non-Small-Cell Lung Cancer Younger and Elderly Patients Treated with a PD-1 Immune Checkpoint Blockade: A Real-World Retrospective Multi-Institutional Analysis

Checkpoint blockade in solid tumors and B-cell malignancies, with special consideration of the role of CD200

Clinical Efficacy of Immunotherapy with Pd-1/Pd-L1 Inhibitors for the Treatment of Advanced Non-Small Cell Lung Cancer

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