Treatment and Survival in Advanced Non-Small Cell Lung Cancer, Urothelial, Ovarian, Gastric and Kidney Cancer: A Nationwide Comprehensive Evaluation

Abstract

Purpose

Few studies have described real-world treatment patterns and survival before the widespread use of immune checkpoint inhibitors (ICIs). We aimed to describe anti-cancer treatment including the use of programmed cell death-1 and ligand-1 (PD-1/PD-L1) ICIs and overall survival (OS) in advanced cancer patients as a benchmarking real-world standard before widespread use of ICIs.

Patients and Methods

Using nationwide Danish medical registries, we assembled cohorts of Danish patients with advanced non-small cell lung cancer (NSCLC) (n=12,283), urothelial carcinoma (n=2504), epithelial ovarian cancer (n=1466), gastric adenocarcinoma (n=1457), and renal cell carcinoma (RCC) (n=1261) diagnosed between 1/1/2013 and 31/12/2017. We describe anti-cancer treatment and OS using proportions, medians, and Kaplan–Meier methods.

Results

Between 9% (ovarian cancer) and 25% (gastric adenocarcinoma) of patients did not receive anti-cancer treatment. The remaining patients received surgery, radiation therapy, and/or medical therapy. Chemotherapy was the most frequent medical therapy in all cohorts except for RCC (tyrosine kinase inhibitors). PD-L1/PD-1 ICIs were used in 7–8% of the NSCLC and RCC cohorts—mainly as second or higher line treatments. OS was longest in patients starting treatment with surgery (eg 25.6 months [95%-confidence interval (CI)=21.9–29.4] for NSCLC and 21.4 months [95%-CI=19.8–23.5] for urothelial carcinoma) and shortest for radiation therapy (eg 3.9 months [95%-CI=3.6–4.2] for NSCLC and 12.6 months [95%-CI=9.2–17.5] for urothelial carcinoma). NSCLC patients starting with medical therapy had OS between these limits. Median OS for NSCLC patients starting treatment with PD-L1/PD-1 ICIs was 21.4 months (95%-CI=13.9-not estimable).

Conclusion

Most patients with advanced NSCLC, urothelial carcinoma, epithelial ovarian cancer, gastric adenocarcinoma and RCC had poor OS in an era where only a minority received PD-L1/PD-1 ICIs. This information on treatment patterns and survival is important as a benchmarking real-world standard before widespread use of ICIs.

Keywords:

• cancer
• treatment
• survival
• immunotherapy
• programmed cell death-1 immune checkpoint inhibitors
• programmed cell death-ligand-1 immune checkpoint inhibitors

Acknowledgments

This work was partly supported by Merck (CrossRef Funder ID: 10.13039/100009945) by an institutional grant to and administered by Aarhus University Hospital, as part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer Inc., New York, NY, USA.

Data Sharing Statement

The data was obtained from the Danish Health Data Authority. We are not allowed to share the data, but the same registry data can be obtained from the Danish Health Data Authority by other researchers fulfilling the requirements.

Ethics Approval and Informed Consent

Under Danish law, ethical permission is not required for registry-based research and it is not required to obtain consent from participants. This study followed the EU General Data Protection Regulation.

Author Contributions

SS and DCF conceived and designed the study, acquired data and interpreted the results. BD designed the study, acquired data and interpreted the results. LR, DO, EB, and PV conceived the study and interpreted the results. AAK, MN, MH, FD and MA designed the study and interpreted the results. SS drafted the manuscript and all other authors revised the manuscript for important intellectual content. All authors have agreed on submission to Clinical Epidemiology, reviewed and agreed on all versions of the manuscript, including the final version, and agreed to be accountable for all the contents of the article.

Disclosure

LR is an employee of Pfizer, and DO, EB, and PV are employees of Merck Healthcare KGaA, Darmstadt, Germany. FD reports receiving research grants from Pfizer, Ipsen, MSD and The Health Research Foundation of Central Denmark Region. AAK reports honoraria from AstraZeneca A/S for speaking at a Nordic-Baltic scientific meeting, “1ST Nordic/Baltic multidisciplinary scientific exchange meeting on treatment of inoperable stage III NSCLC patients” (2019). The authors report no other conflicts of interest in this work.