Clinical impact of pembrolizumab combined with chemotherapy in elderly patients with advanced non-small-cell lung cancer

Morimoto, Kenji; Yamada, Tadaaki; Yokoi, Takashi; Kijima, Takashi; Gotô, Yasuhiro; Nakao, Akira; Hibino, Makoto; Takeda, Takayuki; Yamaguchi, Hiroyuki; Takumi, Chieko; Takeshita, Michinori; Chihara, Yusuke; Yamada, Takahiro; Hiranuma, Osamu; Morimoto, Yoshie; Iwasaku, Masahiro; Uchino, Junichi; Takayama, K.

doi:10.1016/j.lungcan.2021.08.015

Cited by 36 publications

(35 citation statements)

References 32 publications

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“…Several relatively large real-world studies (n ≥100) on first-line chemo-immunotherapy were focused on patients with advanced NSCLC. 18 , 19 , 20 A previous report revealed that the survival estimates were lower than those reported in pivotal clinical trials, 20 whereas other reports have stated that the survival estimates may be as effective as in the clinical trial, in line with our findings. 18 , 19 However, data regarding subsets underrepresented in clinical trials are scarce.…”

Section: Discussionsupporting

confidence: 90%

“… 18 , 19 , 20 A previous report revealed that the survival estimates were lower than those reported in pivotal clinical trials, 20 whereas other reports have stated that the survival estimates may be as effective as in the clinical trial, in line with our findings. 18 , 19 However, data regarding subsets underrepresented in clinical trials are scarce. A recent article included 25 elderly patients who received pemetrexed-based combination therapy and revealed that the PFS and OS rates of the elderly were significantly worse than those of the nonelderly.…”

Section: Discussionsupporting

confidence: 90%

“…A recent article included 25 elderly patients who received pemetrexed-based combination therapy and revealed that the PFS and OS rates of the elderly were significantly worse than those of the nonelderly. 18 However, PD-L1 was not a predictive factor for PFS and OS in this study. Concerning safety, the discontinuation rate of treatment components tended to be higher, but not significantly, in the elderly than in the nonelderly patients in this study.…”

Section: Discussioncontrasting

confidence: 65%

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A Real-World Study on the Effectiveness and Safety of Pembrolizumab Plus Chemotherapy for Nonsquamous NSCLC

Fujimoto

Miura

Yoshimura

et al. 2022

JTO Clinical and Research Reports

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Introduction The real-world effectiveness of combination treatment with cytotoxic chemotherapy and programmed cell death protein-1 or programmed death-ligand 1 inhibitor for NSCLC, especially for the elderly (aged ≥75 y) or those with poor performance status (≥2), has not been fully elucidated. We investigated the real-world effectiveness and safety of this combination therapy in these populations. Methods This multicenter retrospective study evaluated patients who are chemo-naïve with advanced NSCLC who received a combination of platinum, pemetrexed, and pembrolizumab between December 2018 and June 2019. This was an updated prespecified secondary analysis with the primary objective of investigating the safety and effectiveness in this cohort. Results Overall, 299 patients were included. Multivariate analysis identified performance status (0–1) and programmed death-ligand 1 tumor proportion score (≥50%) as significant independent predictors of progression-free survival ( p = 0.007, and p = 0.003, respectively). The incidence of severe adverse events (AEs) was higher in the elderly and those with poor performance status than in their younger and good performance status counterparts. A total of 71 patients developed AEs that led to treatment discontinuation, and AE-related treatment discontinuation occurred at a significantly higher rate in older patients (median [range]) (70 [46–82] y) than in younger patients (68 [31–84] y) ( p <0.001). Conclusions Combination treatment with pembrolizumab plus chemotherapy had low real-world effectiveness for poor performance status patients. Severe AEs occurred at a higher rate in the elderly and poor performance status patients, and the AE-related treatment discontinuation rate increased with age. Physicians should be cautious about using this regimen, especially in the elderly and poor performance status patients.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussioncontrasting

confidence: 65%

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A Real-World Study on the Effectiveness and Safety of Pembrolizumab Plus Chemotherapy for Nonsquamous NSCLC

Fujimoto

Miura

Yoshimura

et al. 2022

JTO Clinical and Research Reports

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“…Nevertheless, elderly patients are often excluded from clinical trials because of their reduced ability to tolerate treatment (e.g., performance score [ECOG PS] ≥2), comorbidities, and potential differences in drug metabolism ( 17 , 18 ). A recent study showed that elderly patients receiving first-line P+C had significantly shorter PFS and OS than younger patients (PFS: 6.2 months vs. 9.7 months, P= 0.004; OS: 11 months vs. not reached, P<0.001) ( 19 ). Elderly patients in our cohort had longer PFS and OS, possibly because there were more stage III patients.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab Plus Chemotherapy Versus Chemotherapy Monotherapy as a First-Line Treatment in Elderly Patients (≥75 Years Old) With Non-Small-Cell Lung Cancer

et al. 2022

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ObjectiveSeveral trials have shown that pembrolizumab plus chemotherapy was more effective in patients with advanced non-small-cell lung cancer (NSCLC) than chemotherapy monotherapy. However, whether pembrolizumab plus chemotherapy is still a better choice for first-line treatment in elderly patients (≥75 years old) remain unknown. We retrospectively compared the efficacy and safety of these two treatments in elderly patients.Patients and MethodsWe collected data of 136 elderly patients with advanced NSCLC who were treated with pembrolizumab plus chemotherapy or chemotherapy monotherapy in our hospital from 2018 to 2020. We compared the progression-free survival (PFS) and overall survival (OS) of patients and analyzed which subgroups might benefit more significantly from pembrolizumab plus chemotherapy.ResultsIn total population, pembrolizumab plus chemotherapy showed superior PFS and OS than chemotherapy monotherapy (PFS: 12.50 months vs. 5.30 months, P<0.001; OS: unreached vs. 21.27 months, P=0.037). Subgroup analysis showed patients with positive PD-L1 expression, stage IV, good performance score (ECOG-PS <2), fewer comorbidities (simplified comorbidity score <9) or female patients had demonstrated a more evident OS benefit in pembrolizumab plus chemotherapy. In terms of safety, the pembrolizumab plus chemotherapy group had higher treatment discontinuation (26% vs. 5%).ConclusionsElderly patients using pembrolizumab plus chemotherapy achieved longer PFS and OS, but were more likely to discontinue due to adverse effects, so disease stage, PD-L1 expression, ECOG-PS and comorbidities should be considered when selecting first-line treatment.

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“…We chose the cut-off of 75 years as patients ≥ 75 years of age demonstrated the greatest disparity between the cancer diagnosis and the clinical trial representation [26]. It is noteworthy to underline that this cut-off was also chosen in many recent studies focusing on the efficacy of PD-1-ICB in elderly NSCLC [27,28]. The percentage of lung cancer cases reached 24.7% in patients ≥ 75 years [29] so our cohort was in line with the existing literature.…”

Section: Discussionmentioning

confidence: 99%

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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Clinical impact of pembrolizumab combined with chemotherapy in elderly patients with advanced non-small-cell lung cancer

Cited by 36 publications

References 32 publications

A Real-World Study on the Effectiveness and Safety of Pembrolizumab Plus Chemotherapy for Nonsquamous NSCLC

A Real-World Study on the Effectiveness and Safety of Pembrolizumab Plus Chemotherapy for Nonsquamous NSCLC

Pembrolizumab Plus Chemotherapy Versus Chemotherapy Monotherapy as a First-Line Treatment in Elderly Patients (≥75 Years Old) With Non-Small-Cell Lung Cancer

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

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