Generalization and representativeness of phase III immune checkpoint blockade trials in non‐small cell lung cancer

Yoo, Seong Ho; Keam, Bhumsuk; Kim, Tae Min; Kim, Dong Wan; Heo, Dae Seog

doi:10.1111/1759-7714.12641

Cited by 34 publications

(25 citation statements)

References 33 publications

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“…Trials with exclusion criteria related to organ-system abnormalities and functional status enroll lower proportions of older patients than trials without such exclusions [6]. Our finding that most older adults with lung cancer are not trial-typical is consistent with previous institutional chart review-based studies, which report that 24-70% of advanced NSCLC patients would be excluded from landmark trials for metastatic lung cancer [28][29][30][31]. Importantly, our findings are based on a population-based study in a country with subsided universal healthcare and likely better reflect the true extent of this problem.…”

Section: Discussionsupporting

confidence: 86%

Are clinical trial eligibility criteria representative of older patients with lung cancer? A population-based data linkage study

Tang

Pearson

Schaffer

et al. 2021

Journal of Geriatric Oncology

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Objectives: Older adults constitute the majority of patients with lung cancer. However, they are underrepresented in clinical trials as eligibility criteria often restrict enrolment based on comorbidities that are common with aging. We aimed to describe comorbidities relating to trial exclusion criteria in older adults with lung cancer, determine the proportion that would typically be excluded from trials, and examine the impact on treatment uptake. Materials and Methods: We conducted a population-based study of people aged ≥65 years diagnosed with metastatic lung cancer using linked data for clients of the Australian Government Department of Veterans' Affairs (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015). We defined trial-typical patients based on the absence of comorbidities related to the following: inadequate organ (cardiac, renal, hepatic, marrow) function; cognitive dysfunction; poor performance status (PS); prior malignancy within 5 years. We report systemic therapy uptake within 3 months of diagnosis. Results: Our study included 677 patients (median age 84). Over half (53.4%) were not trial-typical, with the most common reasons being poor PS (37.5%), cardiac disease (19.2%), and prior cancer (12.9%). Eighty-two (12.1%) received systemic therapy. Patients with poor PS, cardiac disease, and dementia had lower treatment uptake rates. However, there was no significant difference in treatment uptake between trial-typical and non-trial-typical patients (13.4 vs 11.0%). Conclusion: More than half of older adults with advanced lung cancer would be typically excluded from trial participation. Future clinical trials of older adults need to consider broader eligibility criteria to better reflect this population to gain the best evidence for their care.

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Section: Discussionsupporting

confidence: 86%

Are clinical trial eligibility criteria representative of older patients with lung cancer? A population-based data linkage study

Tang

Pearson

Schaffer

et al. 2021

Journal of Geriatric Oncology

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“…6 , 7 Empirical studies of the real-world use of ICIs have estimated that 35%-70% of patients fail to meet strict criteria of PCTs, with recent studies indicating that 55% of patients with melanoma 9 and 70% of patients with non–small-cell lung cancer (NSCLC) would not satisfy eligibility. 10 ICIs are also used for diverse purposes in real-world practice, including off-label usage on the basis of preliminary publications or national guidelines, such as for palliative or maintenance therapy or as an alternative for patients who would not be able to tolerate standard-of-care therapies. 11 - 13 …”

Section: Introductionmentioning

confidence: 99%

Real-World Outcomes for Patients Treated With Immune Checkpoint Inhibitors in the Veterans Affairs System

Cheng

Brophy

et al. 2020

JCO Clinical Cancer Informatics

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PURPOSE Increasingly broad patient groups are being treated with immune checkpoint inhibitors (ICIs) in clinical practice, but few studies have assessed their usage and outcomes in large, comprehensive real-world cohorts. We identified patients who received ICIs in the Veterans Affairs (VA) health care system and described patient characteristics and survival outcomes across multiple indications. METHODS We conducted a retrospective analysis using electronic health record data from VA facilities nationwide. Overall survival (OS) from time of ICI initiation for key indications was estimated by Kaplan-Meier. We also stratified OS by frailty status, as defined by a surrogate index developed in VA data. For select indications, we further compared outcomes to historic and concurrent control patients treated with standard-of-care regimens at the VA. RESULTS We identified 11,888 patients who were treated with ICIs and determined the cancer type and indication for which they were treated. The cohort is enriched for patient groups that are under-represented in pivotal clinical trials (PCTs), including older, non-White, and/or higher disease burdened patients. Generally, OS observed in the VA cohort is lower than that reported in PCTs. After stratifying VA patients by frailty status, OS among nonfrail patients is more similar to OS reported in PCTs for some indications. Compared with internal VA control cohorts, patients treated with ICIs generally exhibited longer OS for all indications considered. CONCLUSION This study describes ICI outcomes across multiple tumor types in a real-world population at the VA. For most indications, real-world survival outcomes are observed to be lower than those reported in PCTs, but patients receiving ICIs still achieve longer survival relative to patients receiving standard of care.

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“…The differences in outcome between RCT- and real-world population-based oncology studies are often believed to emerge from significant differences in the baseline characteristics of study participants. Strict enrolment criteria prevent a majority of RCTs from representing a sizable proportion of real-world patients, ranging from 35% to 70% in non-small cell lung- [4], renal- [5] and colorectal-cancer [6], and melanoma [7].…”

Section: Introductionmentioning

confidence: 99%

“…In conclusion, although RCTs are still the gold-standard practice to evaluate the efficacy (and safety) of a given treatment intervention versus the standard-of-care, real-world studies are critical for understanding whether the results from such RCTs are applicable to the broader population of patients affected by a certain disease. This is particularly true in oncology, where up to two-thirds of real-world patients [4–7] are not represented by current RCTs. As recently highlighted by a joint research statement of the American Society of Clinical Oncology (ASCO) and the Friends of Cancer Research [10], future RCTs should take these issues into account and broaden eligibility criteria to maximize the generalizability of results.…”

Section: Introductionmentioning

confidence: 99%

Real-world evidence to guide healthcare policies in oncology

Donia¹,

Hansen

Svane³

2019

Oncotarget

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Randomized controlled clinical trials (RCTs) in oncology enroll patients who meet strict protocol-specified criteria. Many of these criteria overlap across multiple RCTs. A vast proportion of patients with metastatic cancer do not meet such criteria. Hence, patient populations encountered in clinical practice are essentially different from RCT-populations, questioning the representativeness of these trials. A real-world evidence approach, using data from clinical practice, is increasingly employed to complement the information on drug safety and efficacy obtained from traditional clinical trials.

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Generalization and representativeness of phase III immune checkpoint blockade trials in non‐small cell lung cancer

Abstract: Only 30% of NSCLC patients were eligible for ICB phase III trials. The actual efficacy in the 70% of ineligible patients is unknown. These findings suggest a huge gap between practice-changing phase III trials and the overall population of NSCLC patients.

Cited by 34 publications

References 33 publications

Are clinical trial eligibility criteria representative of older patients with lung cancer? A population-based data linkage study

Are clinical trial eligibility criteria representative of older patients with lung cancer? A population-based data linkage study

Real-World Outcomes for Patients Treated With Immune Checkpoint Inhibitors in the Veterans Affairs System

Real-world evidence to guide healthcare policies in oncology

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