Are Clinical Trial Eligibility Criteria an Accurate Reflection of a Real-World Population of Advanced Non-Small-Cell Lung Cancer Patients?

Al-Baimani, Khalid; Jonker, Hannah; Zhang, T.; Goss, Glenwood D.; Laurie, Scott A.; Nicholas, Garth; Wheatley‐Price, Paul

doi:10.3747/co.25.3978

Cited by 43 publications

(33 citation statements)

References 46 publications

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“…Additionally, clinical trial data may not be representative of the wider population, and may underrepresent clinically important subpopulations. A recent retrospective review of patient records reported that a substantial proportion of patients who failed to meet hypothetical clinical trial eligibility criteria actually received therapy and had similar survival to patients who met the hypothetical eligibility criteria [26].…”

Section: Discussionmentioning

confidence: 99%

Developing real-world comparators for clinical trials in chemotherapy-refractory patients with gastric cancer or gastroesophageal junction cancer

Chau

Ott

et al. 2019

Gastric Cancer

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Background There are few third-line or later (3L+) treatment options for advanced/metastatic (adv/met) gastric cancer/gastroesophageal junction cancers (GC/GEJC). 3L+ Nivolumab demonstrated encouraging results in Asian patients in the ATTRACTION-2 study compared with placebo (12-month survival, 26% vs 11%), and in Western patients in the single-arm CheckMate 032 study (12-month survival, 44%). This analysis aimed to establish comparator cohorts of US patients receiving routine care in real-world (RW) clinical practice. Methods A 2-step matching process generated RW cohorts from Flatiron Health’s oncology database (January 1, 2011–April 30, 2017), for comparison with each trial: (1) clinical trial eligibility criteria were applied; (2) patients were frequency-matched with trial arms for baseline variables significantly associated with survival. Median overall survival (OS) was calculated by Kaplan–Meier analysis from last treatment until death. Results Of 742 adv/met GC/GEJC patients with at least 2 prior lines of therapy, matching generated 90 US RW ATTRACTION-2-matched patients (median OS: 3.5 months) versus 163 ATTRACTION-2 placebo patients (median OS: 4.1 months), and 100 US RW CheckMate 032-matched patients (median OS: 2.9 months) versus 42 CheckMate 032 nivolumab-treated patients (median OS: 8.5 months). Baseline characteristics were generally similar between clinical trial arms and RW-matched cohorts. Conclusions We successfully developed RW cohorts for comparison with data from clinical trials, with comparable baseline characteristics. Survival in US patients receiving RW care was similar to that seen in Asian patients receiving placebo in ATTRACTION-2; survival with nivolumab in CheckMate 032 appeared favorable compared with US RW clinical practice.

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Section: Discussionmentioning

confidence: 99%

Developing real-world comparators for clinical trials in chemotherapy-refractory patients with gastric cancer or gastroesophageal junction cancer

Chau

Ott

et al. 2019

Gastric Cancer

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“…Previous studies using different study approaches have demonstrated that as many as 80% of real-world patients may be ineligible to participate in clinical trials [ [6] , [7] , [8] , [9] , [10] ] [ [6] , [7] , [8] , [9] , [10] ] [ [6] , [7] , [8] , [9] , [10] ]. The common reasons cited for ineligibility include advanced age and the presence of specific comorbid conditions such as cardiovascular disease, hepatic dysfunction, and chronic kidney failure [ 6 , 8 ]. This contrasts the demographics of real-world patients with cancer who tend to be older and who are more likely to have comorbid conditions than their younger counterparts [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Eligibility of real-world patients with metastatic breast cancer for clinical trials

2020

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Introduction The results of clinical trials in metastatic breast cancer (MBC) are generalized to real-world patients. This study determines the proportion of real-world patients who would be eligible for clinical trials and compares outcomes in eligible versus ineligible patients. Methods Patients diagnosed with MBC from 2004 to 2015 in a large Canadian province were included. Patients with one of the following criteria were considered ineligible: the presence of comorbid conditions (anemia, uncontrolled diabetes, heart disease, liver disease, and kidney disease) or a history of immunosuppression or prior malignancy. The likelihood of receiving cancer therapy was analysed using logistic regression models and factors affecting overall survival (OS) were assessed by Cox proportional hazards models. Results A total of 1585 patients with MBC were identified. The median age at diagnosis was 63 years. Of these, 512 (32.3%) patients were deemed ineligible in whom the two most common reasons for ineligibility were renal dysfunction (17.2%), and previous immunosuppression (7.8%). In the real world, ineligible patients were less likely to receive chemotherapy (29.5% vs 45.8%; P < 0.001) but not radiation treatment (7.6% vs 9.6%; P = 0.196) or hormonal therapy (57.6% vs 60.6%; P = 0.261). The 5-year OS of ineligible patients who received systemic therapy in the real-world was significantly better than those who did not. Conclusions Despite being ineligible for clinical trials based on common eligibility criteria, many real-world patients receive systemic treatment and derive possible benefit. Broadening of inclusion criteria in clinical trials will enhance the representation of real-world patients and increase the generalizability of results.

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“…All the aforementioned led us to propose to the Cuban Regulatory Authority (CECMED), the initiation of a compassionate use program (CUP) for CIGB-247 in cancer patients that did not meet the strict entry criteria applied for the CENTAURO and CENTAURO-2 clinical trials, but could potentially benefit from the application of CIGB-247. It is well known that a large proportion of cancer patients with life-threatening disease are excluded from clinical trials, despite the fact that these subjects are better reflections of the real-world population of cancer patients [25].…”

Section: Introductionmentioning

confidence: 99%

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program

et al. 2020

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Background: CIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterially-derived adjuvant VSSP. CIGB-247 has been already evaluated in two phase I clinical trials (CENTAURO and CENTAURO-2), showing to be safe and immunogenic in advanced cancer patients selected under well-defined and controlled clinical conditions. Surviving patients were submitted to monthly re-immunizations and some of them showed objective clinical benefits. Based on these results, a compassionate use program (CUP) with CIGB-247 was initiated for patients that did not meet the strict entry criteria applied for the CENTAURO and CENTAURO-2 clinical trials, but could potentially benefit from the application of this cancer therapeutic vaccine. Results: Polyclonal IgM, IgA and IgG antibodies specific for VEGF were detected by ELISA in serum samples from patients vaccinated with 400 μg of antigen combined with 200 μg of VSSP. Polyclonal antibody response showed no cross reactivity for other VEGF family member molecules like VEGF-C and VEGF-D. Serum from immunized individuals was able to block the binding of VEGF to its receptors VEGFR2 and VEGFR1. IgG fraction purified from immune sera shared the aforementioned characteristics and also inhibited the interaction between VEGF and the therapeutic recombinant antibody bevacizumab, an anti-angiogenic drug approved for the treatment of different tumors. No serious adverse events attributable to CIGB-247 have been documented yet in participants of the CIGB-247 CUP. The present paper is a first report of our findings concerning the humoral response and safety characteristics in treated CIGB-247 CUP cancer patients. The study has provided the unique opportunity of not only testing CIGB-247 in a broader clinical spectrum sample of Cuban cancer patients, but also within the context of the day-today clinical practice and treatment settings for these diseases in Cuban medical institutions.

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Are Clinical Trial Eligibility Criteria an Accurate Reflection of a Real-World Population of Advanced Non-Small-Cell Lung Cancer Patients?

Abstract: Background Advanced non-small-cell lung cancer (nsclc) represents a major health issue globally. Systemic

Cited by 43 publications

References 46 publications

Developing real-world comparators for clinical trials in chemotherapy-refractory patients with gastric cancer or gastroesophageal junction cancer

Developing real-world comparators for clinical trials in chemotherapy-refractory patients with gastric cancer or gastroesophageal junction cancer

Eligibility of real-world patients with metastatic breast cancer for clinical trials

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program

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