Risk factors for skeletal-related events in non-small cell lung cancer patients treated with bone-modifying agents

Support Care Cancer. 2021 Jul;29(7):4081-4088. doi: 10.1007/s00520-020-05880-5. Epub 2021 Jan 6.

Abstract

Purpose: The risk factors for skeletal-related events (SREs) among non-small cell lung cancer (NSCLC) patients during treatment with bone-modifying agents (BMAs) are not yet well-understood.

Methods: The medical records of 238 consecutive NSCLC patients treated with BMAs, including zoledronic acid and denosumab, at the Chiba University Hospital from 2012 to 2016 were reviewed in the present study. SREs were defined as either pathologic fractures, spinal cord compression, the need for bone irradiation or surgery, or hypercalcemia. The risk factors for earlier occurrence of the first SRE from the time of the first bone metastasis diagnosis after the initiation of BMA treatment were identified.

Results: Of the 238 included patients, 92% (n = 220) had a performance status (PS) of 0-2 at diagnosis of bone metastasis. Forty-eight (20%) patients developed at least one SRE. The most common first SRE was the need for bone irradiation surgery (n = 27, 56%). Significant risk factors included poor PS (hazard ratio [HR]: 4.36; p = .024), male sex (HR: 2.17; p = .022), and the use of zoledronic acid (HR: 1.91; p = .032). The overall survival (OS) from the first bone metastasis diagnosis was 394 days (95% confidence interval [CI]: 331-465). The OS of patients with PS 3 and 4 at the diagnosis of bone metastasis (median: 36 days; 95% CI: 13-50) was significantly (p < 0.0001) shorter than that of patients with PS 0-2 (median: 411 days; 95% CI: 354-558) (HR: 4.53; 95% CI: 2.62-7.35).

Conclusions: Careful observation is needed for patients with the identified risk factors, which include poor PS and male sex, despite the BMA treatment.

Keywords: Bone metastasis; Bone-modifying agent; Non-small cell lung cancer; Risk factor; Skeletal-related event.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Density Conservation Agents / adverse effects*
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / secondary
  • Bone and Bones / pathology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Denosumab / adverse effects*
  • Denosumab / therapeutic use
  • Female
  • Fractures, Spontaneous / complications
  • Humans
  • Hypercalcemia / complications
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • Spinal Cord Compression / complications
  • Zoledronic Acid / adverse effects*
  • Zoledronic Acid / therapeutic use

Substances

  • Bone Density Conservation Agents
  • Denosumab
  • Zoledronic Acid