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      Use of a Cancer Registry to Evaluate Patient-Reported Outcomes of Immune Checkpoint Inhibitors

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          Abstract

          Simple Summary

          Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, but few studies have reported on patient-reported outcomes (PROs) outside the context of a clinical trial. The goal of the current study was to assess PROs in patients participating in the GO 2 Foundation’s Lung Cancer Registry who reported receiving atezolizumab, durvalumab, nivolumab, or pembrolizumab. Internationally, 226 patients (mean age 61, 75% female) participated. Patients reported worse quality of life than U.S. population and cancer normative samples. The most common moderate to severe adverse events during ICI treatment were fatigue (41%), aching joints (27%), and aching muscles (20%). Due to toxicity, 25% reported a treatment delay, 11% an emergency room visit, and 9% a hospitalization. This study is among the first to our knowledge to report on PROs of ICIs outside the context of a clinical trial. Results suggest higher rates of adverse events than previously reported in clinical trials.

          Abstract

          Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, but few studies have reported on patient-reported outcomes (PROs) outside the context of a clinical trial. The goal of the current study was to assess PROs in participants of a lung cancer registry who had been treated with an ICI. Patients participating in the GO 2 Foundation’s Lung Cancer Registry who reported receiving atezolizumab, durvalumab, nivolumab, or pembrolizumab were invited to participate in a survey about their experiences during treatment. Quality of life was evaluated using the Functional Assessment of Cancer Therapy–General (FACT-G). Common symptomatic adverse events were evaluated using an item bank generated for ICIs. Internationally, 226 patients (mean age 61, 75% female) participated. Patients reported worse quality of life at the time of assessment than U.S. population and cancer normative samples. The most common moderate to severe adverse events during ICI treatment were fatigue (41%), aching joints (27%), and aching muscles (20%). Due to toxicity, 25% reported a treatment delay, 11% an emergency room visit, and 9% a hospitalization. This study is among the first to our knowledge to report on PROs of ICIs outside the context of a clinical trial. Results suggest higher rates of adverse events than previously reported in clinical trials.

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          Most cited references36

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          A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation

          The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
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            Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial.

            Despite recent advances in the treatment of advanced non-small-cell lung cancer, there remains a need for effective treatments for progressive disease. We assessed the efficacy of pembrolizumab for patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer.
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              Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer

              We assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit. We assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review. Common side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all the patients, the objective response rate was 19.4%, and the median duration of response was 12.5 months. The median duration of progression-free survival was 3.7 months, and the median duration of overall survival was 12.0 months. PD-L1 expression in at least 50% of tumor cells was selected as the cutoff from the training group. Among patients with a proportion score of at least 50% in the validation group, the response rate was 45.2%. Among all the patients with a proportion score of at least 50%, median progression-free survival was 6.3 months; median overall survival was not reached. Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab. (Funded by Merck; KEYNOTE-001 ClinicalTrials.gov number, NCT01295827.).
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                31 December 2020
                January 2021
                : 13
                : 1
                : 103
                Affiliations
                [1 ]Moffitt Cancer Center, Department of Health Outcomes and Behavior, Tampa, FL 33612, USA; Sarah.Eisel@ 123456moffitt.org (S.L.E.); Aasha.Hoogland@ 123456moffitt.org (A.I.H.)
                [2 ]GO 2 Foundation for Lung Cancer, Washington, DC 20006, USA; sshaw@ 123456mjhlifesciences.com (S.S.); jking@ 123456go2foundation.org (J.C.K.)
                [3 ]Jefferson Center for Digital Health, Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA; Adam.Dicker@ 123456jefferson.edu
                Author notes
                Author information
                https://orcid.org/0000-0002-8691-8132
                https://orcid.org/0000-0003-0733-3337
                Article
                cancers-13-00103
                10.3390/cancers13010103
                7795027
                33396286
                557280e5-65a8-4fe9-a038-99f64b0aa9af
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 November 2020
                : 22 December 2020
                Categories
                Article

                antineoplastic agents,immunological,programmed cell death receptor 1,lung neoplasms,quality of life,patient-reported outcome measures

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