Reporting of Incidence and Outcome of Bone Metastases in Clinical Trials Enrolling Patients with Epidermal Growth Factor Receptor Mutated Lung Adenocarcinoma-A Systematic Review

Anita Brouns, Safiye Dursun, Gerben Bootsma, Anne-Marie C. Dingemans, Lizza Hendriks*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review


Simple Summary Around 30-60% of the patients with lung cancer develop bone metastases, which are associated with decreased survival, bone pain, and skeletal-related events such as need for radiation. Patients with an epidermal growth factor mutation (EGFR), a subgroup of the patients with lung cancer, seem to develop more bone metastases than other patients with lung cancer. Due to prolonged survival of these patients, they live longer with bone metastases and/or skeletal-related events, therefore optimal management is warranted. The aim of our systematic review is to gain more insight in reporting of bone metastases, skeletal-related events, and bone-specific outcome of treatment in clinical trials enrolling patients with EGFR-mutated lung cancer. We found that data on bone metastases and bone-related outcomes are largely lacking in clinical trials. There should be more focus on reporting and preventing of skeletal-related events in these patients. Bone metastases, occurring in 30-60% of patients with non-small cell lung cancer (NSCLC), are associated with decreased survival, cancer-induced bone pain, and skeletal-related events (SREs). Those with an activating epidermal growth factor mutation (EGFR+) seem to be more prone to develop bone metastases. To gain more insight into bone metastases-related outcomes in EGFR+ NSCLC, we performed a systematic review on Pubmed (2006-2021). Main inclusion criteria: prospective, phase II/III trials evaluating EGFR-tyrosine kinase inhibitors, >= 10 EGFR+ patients included, data on bone metastases and/or bone-related outcomes available. Out of 663 articles, 21 (3176 EGFR+ patients) met the eligibility criteria; 4 phase III (one double blind), 17 phase II trials (three randomized) were included. In seven trials dedicated bone imaging was performed at baseline. Mean incidence of bone metastases at diagnosis was 42%; 3-33% had progression in the bone upon progression. Except for one trial, it was not specified whether the use of bone target agents was permitted, and in none of the trials, occurrence of SREs was reported. Despite the high incidence of bone metastases in EGFR+ adenocarcinoma, there is a lack of screening for, and reporting on bone metastases in clinical trials, as well as permitted bone-targeted agents and SREs.

Original languageEnglish
Article number3144
Number of pages20
Issue number13
Publication statusPublished - Jul 2021


  • non-small cell lung cancer
  • lung adenocarcinoma
  • epidermal growth factor mutation
  • bone metastases
  • skeletal-related events
  • epidermal growth factor receptor mutation
  • tyrosine kinase inhibitor
  • CELL

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