Clinical outcomes of ALK+ non-small cell lung cancer in Denmark

Abstract

Background

Real-world clinical outcomes of anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) patients vary. This study aimed to investigate the treatment and clinical outcomes of all ALK+ NSCLC patients in Denmark in the period 2011–2018, regardless of disease stage.

Materials and Methods

A national pathology database with complete coverage was used to identify ALK+ NSCLC patients diagnosed between 2011 and 2018. Clinical data were obtained through retrospective chart reviews. Overall survival (OS) and duration of treatment (DOT) were analyzed using Kaplan-Meier methodologies.

Results

A total of 209 ALK+ NSCLC patients were included. The cohort had a slight overrepresentation of female patients (56.5%) with a mean age of 61.6 years. Most patients were adenocarcinoma cases (97%) and presented with an ECOG performance status of 0–1 (79%). Stage IIIb–IVb patients comprised 70% of the cohort. The use of ALK-tyrosine kinase inhibitors (TKIs) as first-line treatment increased over time, with the 1st generation ALK-TKI crizotinib being the predominant treatment in the 1st line. In 1st line treatment, 2nd generation ALK-TKIs had a median DOT more than twice the median DOT of crizotinib (25.1 and 9.1 months, respectively). The median OS for the entire cohort was 44.0 months. Patients with stage I–IIIA disease had a median OS that had not been reached, while those with stage IIIb–IVb disease had a median OS of 31.8 months. Patients with stage IIIb–IVb disease receiving an ALK-TKI as 1st line treatment had a median OS of 42.5 months with immature follow-up. Brain metastases at diagnosis or choice of 1st line treatment did not statistically significantly impact OS.

Conclusion

This study gives insights into the treatment and outcome of ALK+ NSCLC patients in Denmark and provides a real-world confirmation of the superior disease control provided by 2nd generation ALK-TKIs as compared to the 1st generation ALK-TKI crizotinib.

Keywords:

• nationwide
• ALK+non-small cell lung cancer
• retrospective
• prevalence
• clinical outcome
• treatment use and duration

Author contributions

All authors contributed to the study’s conception and design. Data collection was performed by Jakob Sidenius Johansen, Peter Hjorth-Hansen, Maiken Parm Ulhøi, Edyta Maria Urbanska, Karin Holmskov Hansen, and Charlotte Kristiansen. Data analysis were performed by Anders Bondo Dydensborg. The first draft of the manuscript was written by Anders Bondo Dydensborg, and all authors reviewed the manuscript critically. All authors read and approved the final manuscript

Ethics approval

The study was approved by the Danish Patient Safety Authority (#3-3013-3274/1) and registered at the Danish Data Protection Agency. There are no Danish legislation requirements to obtain informed consent from the patients to use the data in this study, as the patients were not contacted at any point during this study, the study did not affect the treatment of the patients, and only pseudonymized data were used.

Disclosure statement

The authors ABD and CD are employees of Takeda Pharma A/S. PM has received research funding from Roche, Takeda, and Astra Zeneca, as well as consultancy fees from Amgen, Astra Zeneca, Roche, Sanofi, Pfizer, and Takeda. EMU has received honorarium and consultancy fees from Roche, Amgen, Astra Zeneca, Novartis, Takeda, and Pfizer. ES-R has received consultancy/lecture honorarium from Amgen, Bayer, Roche, Sanofi, Takeda Astra Zeneca, Bristol Myers Squibb, Roche, Takeda, conference participation support from Takeda, and research grants from Roche and Sanofi. MPU has received consultancy/lecture honorarium from Takeda, Pfizer, Amgen, and Sanofi as well as conference participation support from Sanofi and MSD. JLA has received honoraria for lectures, advisory boards, and congress expenses from Abbvie, Amgen, Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck Sharp, and Dohme (MSD), Novartis, Pfizer, Pierre Fabre, Roche, Sanofi and Takeda. MS has received honoraria for lectures and advisory board from Takeda. All other authors report no other conflicts of interest in this work. Author JSJ’s employment at the Dept. of Oncology, Herlev Hospital ended during the writing of the article, JSJ is now employed at Nordic Medicare, Rungsted Kyst, Denmark.

Data availability statement

The participants of this study did not give written consent for their data to be shared publicly, so due to the sensitive nature of the research supporting data is not available.

Additional information

Funding

This work was funded and initiated by Takeda Pharma A/S, a subsidiary of Takeda Pharmaceuticals Inc.