Checkpoint inhibitor immunotherapy toxicity and overall survival among older adults with advanced cancer

Johns, Andrew; Wei, Lai; Grogan, Madison; Hoyd, Rebecca; Bridges, John F.P.; Patel, Sandipkumar; Li, Mingjia; Husain, Marium; Kendra, Kari; Burkart, Jarred; Rosko, Ashley; Andersen, Barbara L.; Carbone, David P.; Owen, Dwight H.; Spakowicz, Daniel; Presley, Carolyn J.

doi:10.1016/j.jgo.2021.02.002

Cited by 28 publications

(22 citation statements)

References 29 publications

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“…These results of effectiveness were different from ours, but the results concerning safety had a similar trend. Although several previous studies of immunotherapy have shown that increased age was not associated with a higher irAE rate, 21 , 22 , 23 , 24 the clinical trials of cytotoxic agents for the elderly revealed a higher rate of AEs. 25 , 26 In addition, a trend toward lower effectiveness of chemotherapy plus pembrolizumab was noted with an apparent detrimental effect in participants aged more than or equal to 75 years in the KEYNOTE-189 trial.…”

Section: Discussionmentioning

confidence: 74%

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: Discussionmentioning

confidence: 74%

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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“…On the other hand, local therapies are able to address the puzzle of drug resistance in tumors after systemic therapies. However, some researchers believe that local therapies will provide a certain drug-free interval, thereby reducing adverse events caused by systemic therapies and maintaining the quality of life ( 34 , 35 ). Therefore, local therapies should precede system therapies.…”

Section: Discussionmentioning

confidence: 99%

Metastatic Clear Cell Renal Cell Carcinoma to Pancreas and Distant Organs 24 Years After Radical Nephrectomy: A Case Report and Literature Review

Cao

Sun

et al. 2022

Front. Surg.

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BackgroundClear cell renal cell carcinoma (CCRCC) is a common urological neoplasm, and even though surgical resection is effective for localized CCRCC, the prognosis of metastatic CCRCC is poor. Currently, there is a paucity of recognized effective therapeutic protocols for metastatic CCRCC.Case presentationA 76-year-old Asian man underwent radical left nephrectomy for CCRCC 26 years ago; this patient visited our hospital with abdominal pain due to multiple abdominal metastases 24 years after the nephrectomy. After metastasectomy, he underwent targeted therapy combined with a programmed death receptor-1 (PD-1) inhibitor, and the current imaging results indicate remarkable tumor remission.ConclusionsMetachronous pancreatic metastasis from CCRCC after nephrectomy is rare, but clinicians and patients should not ignore this possibility. The combination of targeted therapy and immunotherapy can result in satisfactory outcomes in cases where metastatic CCRCC continues to progress despite metastasectomy and targeted therapy. The combination of local and systemic therapy can be an effective therapeutic protocol for metastatic CCRCC, but there is no consensus on suitable therapeutics.

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“…One study showed a modestly high rate of irAEs and early treatment discontinuation in patients above 80 years 72. Another study demonstrated improvement in OS for younger patients who experienced high-grade irAEs compared with those who did not, however, there was no improvement in OS among patients over 70 with high-grade irAEs 73▪.…”

Section: Immunotherapy Toxicity In Older Patientsmentioning

confidence: 99%

Immunotherapy for older patients with cancer

Vargas

Al-Humiqani

Mata

et al. 2023

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of the review The aim of this review is to describe the clinical use and tolerability of immune checkpoint inhibitors in older adults with solid tumors, where there is an abundance of evidence with recent updates including subgroups of older patients. Recent findings Studies with updated analyses and subgroups of older patients show that in general older patients benefit as well as younger patients and tolerate immunotherapy very well. However, in some instances of combination therapies which may expose patients to more toxicity, the benefits are reduced, and careful selection of older patients, including adjunctive assessments such as geriatric assessment, can help to identify the appropriate treatment for an individual patient. Summary Older adults remain underrepresented in clinical trials, including those involving immunotherapy. Therefore, efforts must be made to include more older patients in trials and to assess real-world evidence to inform decision-making.

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Checkpoint inhibitor immunotherapy toxicity and overall survival among older adults with advanced cancer

Cited by 28 publications

References 29 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

Metastatic Clear Cell Renal Cell Carcinoma to Pancreas and Distant Organs 24 Years After Radical Nephrectomy: A Case Report and Literature Review

Immunotherapy for older patients with cancer

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