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. 2020 Mar 2;3(3):e200643.
doi: 10.1001/jamanetworkopen.2020.0643.

Association of Disease Progression With Health-Related Quality of Life Among Adults With Breast, Lung, Pancreatic, and Colorectal Cancer

Norbert Marschner  1 , Stefan Zacharias  2   3 , Florian Lordick  4 , Susanna Hegewisch-Becker  5 , Uwe Martens  6 , Anja Welt  7 , Volker Hagen  8 , Wolfgang Gleiber  9 , Sabine Bohnet  10 , Lisa Kruggel  11 , Stephanie Dille  12 , Arnd Nusch  13 , Steffen Dörfel  14 , Thomas Decker  15 , Martina Jänicke  11
Affiliations

Association of Disease Progression With Health-Related Quality of Life Among Adults With Breast, Lung, Pancreatic, and Colorectal Cancer

Norbert Marschner et al. JAMA Netw Open. .

Abstract

Importance: Mortality, morbidity, and health-related quality of life (HRQoL) are patient-relevant end points generally considered in the early benefit assessments of new cancer treatments. Progression-related end points, such as time to progression or progression-free survival, are not included, although patients and physicians testify to the detrimental association of disease progression with HRQoL.

Objective: To examine the association of disease progression and HRQoL in 4 prevalent solid-cancer entities in routine clinical practice.

Design, setting, and participants: This cohort study evaluated data from 4 prospective, nonintervention, multicenter registries collected between 2011 and 2018 in 203 centers in Germany. Patients' HRQoL was assessed regularly for up to 5 years. The change in HRQoL scores after disease progression was examined with linear mixed models, adjusting for demographic and clinical covariates. Patients with metastatic breast, pancreatic, lung, and colorectal cancer were recruited at the start of systemic first-line treatment. Data analysis was performed from February 2019 to April 2019.

Exposures: All patients received systemic, palliative first-line treatment according to their physician's choice.

Main outcomes and measures: The primary outcome was deterioration of HRQoL associated with disease progression, as measured by 4 validated questionnaires: Functional Assessment of Cancer Therapy-General version 4, European Organization for Research and Treatment of Cancer QLQ-C30 version 3.0, European Organization for Research and Treatment of Cancer QLQ-C15-PAL version 1, and Hospital Anxiety and Depression Scale.

Results: More than 8000 questionnaires from 2314 patients with 2562 documented disease progressions were analyzed. In total, 464 patients had breast cancer (464 [100.0%] female; median [range] age, 61.6 [26.4-90.1] years), 807 patients had pancreatic cancer (352 [43.6%] female; median [range] age, 70.0 [39.0-93.0] years), 341 patients had lung cancer (118 [34.6%] female; median [range] age, 65.9 [28.4-88.2] years), and 702 patients had colorectal cancer (248 [35.3%] female; median [range] age, 66.9 [26.9-92.1] years). The first disease progression was associated with a statistically significant worsening of 37 of 45 HRQoL scales; for 17 of these scales, the worsening was clinically meaningful. Scale scores for appetite loss (pancreatic cancer, 10.2 points [95% CI, 6.8-13.5 points]; lung cancer, 10.8 points [95% CI, 5.4-16.2 points]; colorectal cancer, 8.8 points [95% CI, 5.5-12.2]; all P < .001), physical functioning (pancreatic cancer, 6.2 points [95% CI, 3.8-8.5 points]; lung cancer, 8.4 points [95% CI, 5.4-11.5 points]; colorectal cancer, 5.0 points [95% CI, 3.0-7.0 points]; all P < .001), and fatigue (pancreatic cancer, 5.5 points [95% CI, 3.0-7.9 points]; lung cancer, 7.7 points [95% CI, 4.3-11.1]; colorectal cancer, 4.5 points [95% CI, 2.1-6.9 points]; all P < .001) were most affected, irrespective of the type of cancer. The association with global HRQoL was most pronounced in lung cancer (6.7 points [95% CI, 3.5-9.9 points]; P < .001) and pancreatic cancer (5.4 points [95% CI, 3.3-7.5 points]; P < .001) and less in colorectal cancer (3.5 points [95% CI, 1.3-5.7 points]; P = .002) and breast cancer (2.4 points [95% CI, 1.0-3.9 points]; P = .001). The second progression was associated with an even larger decrease in HRQoL.

Conclusions and relevance: These findings suggest that disease progression is associated with a deterioration in HRQoL among patients with metastatic breast, pancreatic, lung, and colorectal cancer. This evidence highlights the importance of progression-related end points, such as time to progression and progression-free survival, as additional patient-relevant end points when evaluating the benefit of new treatments for patients with metastatic cancer.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Marschner reported receiving personal fees from Roche, Novartis, Celgene, TEVA, Amgen, and Böhringer Ingelheim and remuneration for the documentation of patient data from iOMEDICO outside the submitted work; Dr Marschner also is chief executive officer and shareholder of iOMEDICO AG. Dr Welt reported receiving personal fees from Roche, Amgen, Pfizer, Lily, Tesaro, AstraZeneca, and Eisai and grants and personal fees from Novartis outside the submitted work. Dr Hagen reported receiving remuneration for the documentation of patient data from iOMEDICO during the conduct of the study; personal fees from Roche, Pfizer, and FomF; and personal fees and remuneration for the documentation of patient data from Celgene, BMS, JNJ, Novartis, and Gilead outside the submitted work. Dr Gleiber reported receiving remuneration for the documentation of patient data from iOMEDICO. Outside of the published work, the institutions of Drs Lordick, Hegewisch-Becker, Bohnet, Nusch, and Dörfel received remuneration for the documentation of patient data. Dr Decker reported receiving personal fees from Novartis and remuneration for the documentation of patient data from iOMEDICO outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Linear Mixed Model for Association of First Disease Progression With Quality of Life (QoL) and Symptoms
A, Association of first progression with scales of the Functional Assessment of Cancer Therapy–General version 4 (FACT-G) and Hospital Anxiety and Depression Scale (HADS) questionnaires among patients with breast cancer. B, Association of first progression with scales and symptoms of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15 questionnaire among patients with pancreatic cancer. C, Association of first progression with scales and symptoms of the EORTC QLQ-C30 questionnaire among patients with lung cancer. D, Association of first progression with scales and symptoms of the EORTC QLQ-C30 questionnaire among patients with colorectal cancer. Numbers indicate number of questionnaires completed by patients after their first and before the second disease progression. CF indicates cognitive functioning; EF, emotional functioning; EWB, emotional well-being; FWB, functional well-being; PF, physical functioning; PWB, physical well-being; RF, role functioning; SF, social functioning; and SWB, social well-being.
Figure 2.
Figure 2.. Linear Mixed Model for Association of Second Disease Progression With Quality of Life (QoL) and Symptoms
A, Association of second progression with scales of the Functional Assessment of Cancer Therapy–General version 4 (FACT-G) and Hospital Anxiety and Depression Scale (HADS) questionnaires among patients with breast cancer. B, Association of second progression with scales and symptoms of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15 questionnaire among patients with pancreatic cancer. C, Association of second progression with scales and symptoms of the EORTC QLQ-C30 questionnaire among patients with lung cancer. D, Association of second progression with scales and symptoms of the EORTC QLQ-C30 questionnaire patients with colorectal cancer. Numbers indicate number of questionnaires completed by patients after their second and before the third disease progression. CF indicates cognitive functioning; EF, emotional functioning; EWB, emotional well-being; FWB, functional well-being; PF, physical functioning; PWB, physical well-being; RF, role functioning; SF, social functioning; and SWB, social well-being.
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