Clinical features affecting efficacy of immune checkpoint inhibitors in pretreated patients with advanced NSCLC: a Danish nationwide real-world study

Abstract

Background

Immune checkpoint inhibitors (ICIs) are implemented as standard treatment for patients with advanced non-small cell lung cancer (NSCLC) in first-line and subsequent-line treatment. However, certain subgroups such as patients with older age, poor performance status (PS), and severe comorbidity are underrepresented in the randomized controlled trials (RCTs). This study aimed to assess overall survival (OS), treatment data, and clinical features affecting second- or subsequent-line ICI efficacy in an unselected, Danish, nationwide NSCLC population.

Methods

Patients with advanced NSCLC who started nivolumab or pembrolizumab as second-line or subsequent-line treatment between 1 September 2015, and 1 October 2018, were identified from institutional records of all Danish oncology departments. Clinical and treatment data were retrospectively collected. Descriptive statistics and survival analyses were performed.

Results

Data were available for 840 patients; 49% females. The median age was 68 years (19% were ≥75 years), 19% had PS ≥2, and 36% had moderate to severe comorbidity. The median OS (mOS) was 12.2 months; 15.1 months and 10.0 months in females and males, respectively. The median time-to-treatment discontinuation (mTTD) and median progression-free survival (mPFS) was 3.2 and 5.2 months, respectively. Patients with PS ≥2 had a mOS of 4.5 months, mTTD of 1.1 month, and mPFS of 2.0 months. In multivariable Cox regression analysis, male sex (HR = 1.35, 95% CI 1.11–1.62), PS >0 (PS 1, HR = 1.88, 95% CI 1.52–2.33; PS ≥2, HR = 4.15, 95% CI 3.13–5.5), liver metastases (HR = 1.72, 95% CI 1.34–2.22), and bone metastases (HR = 1.27, 95% CI 1.03–1.58) were significant poor prognostic OS factors.

Conclusions

Danish real-world patients with advanced NSCLC treated with second- or subsequent-line ICI had an OS comparable to results from RCTs. Women, frail and older patients constituted a higher proportion than in previous RCTs. Clinical features associated with poor OS were male sex, PS ≥1 (in particular PS ≥2), bone-, and liver metastases.

Keywords:

• Cancer immunotherapy
• clinical prognostic factors
• immune-checkpoint inhibitors
• non-small cell lung cancer
• real-world evidence

Acknowledgements

The authors thank Professor Ursula G. Falkmer, MD, PhD, Clinical Cancer Research Center, Departments of Clinical Medicine and Oncology, Aalborg University and Aalborg University Hospital for contributing to the writing process.

Ethics approval and consent to participate

Approved by the Danish Patient Safety Authority and reported to The Danish Data Protection Agency.

Consent for publication

Patient consent was waived by the Danish Patient Safety Authority, due to the retrospective design of the study, and the use of routinely collected data.

Disclosure statement

The funding sources were not involved in the study design, collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the article for publication. GF Persson: Advisory board Roche, Astra Zeneca, BMS, MSD, Takeda, Pfizer. Congress travels with Roche, Astra Zeneca, BMS, MSD, Takeda, Pierre Fabre. Research grants from Varian Medical Systems. M Pøhl: Honoraria for lectures and consultancy from AstraZeneca, BMS, MSD, Pfizer, Roche. SW Langer: Advisory board MSD, Roche, Pfizer. The remaining authors declare no conflict of interest.

Data availability statement

The study data may be available on request from the corresponding author, Mette T Mouritzen. The data are not publicly available due to the General Data Protection Regulation.

Additional information

Funding

The study was supported by the Danish Health Authority’s ‘Cancer Immunotherapy Research Grant’ [05-0400-44] and the Medical Fund of the Danish Regions. The funding sources were not involved in the study design or in the collection, analysis and interpretation of data. Furthermore, they were not involved in the writing of the report or in the decision to submit the article for publication.