Bone Metastases, Skeletal-Related Events, and Survival in Patients With Metastatic Non–Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

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  • 1 Division of Hematology and Oncology, University of Michigan, Ann Arbor, Michigan;
  • | 2 Center for Biostatistics,
  • | 3 Division of Medical Oncology, and
  • | 4 Department of Internal Medicine, The Ohio State University, Columbus, Ohio;
  • | 5 Division of Hematology and Oncology, Henry Ford Cancer Center, Detroit, Michigan;
  • | 6 Department of Hematology and Oncology, Cleveland Clinic, Cleveland, Ohio; and
  • | 7 Department of Neurosurgery,
  • | 8 Department of Medical Education, and
  • | 9 Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
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Background: Bone metastases and skeletal-related events (SREs) are a frequent cause of morbidity in patients with metastatic non–small cell lung cancer (mNSCLC). Data are limited on bone metastases and SREs in patients with mNSCLC treated using immune checkpoint inhibitors (ICIs), and on the efficacy of bone-modifying agents (BMAs) in this setting. Here we report the incidence, impact on survival, risk factors for bone metastases and SREs, and impact of BMAs in patients with mNSCLC treated with ICIs in a multi-institutional cohort. Patients and Methods: We conducted a retrospective study of patients with mNSCLC treated with ICIs at 2 tertiary care centers from 2014 through 2017. Overall survival (OS) was compared between patients with and without baseline bone metastases using a log-rank test. A Cox regression model was used to evaluate the association between OS and the presence of bone metastases at ICI initiation, controlling for other confounding factors. Results: We identified a cohort of 330 patients who had received ICIs for metastatic disease. Median patient age was 63 years, most patients were treated in the second line or beyond (n=259; 78%), and nivolumab was the most common ICI (n=211; 64%). Median OS was 10 months (95% CI, 8.4–12.0). In our cohort, 124 patients (38%) had baseline bone metastases, and 43 (13%) developed SREs during or after ICI treatment. Patients with bone metastases had a higher hazard of death after controlling for performance status, histology, line of therapy, and disease burden (hazard ratio, 1.57; 95% CI, 1.19–2.08; P=.001). Use of BMAs was not associated with OS or a decreased risk of SREs. Conclusions: Presence of bone metastases at baseline was associated with a worse prognosis for patients with mNSCLC treated with ICI after controlling for multiple clinical characteristics. Use of BMAs was not associated with reduced SREs or a difference in survival.

Submitted April 30, 2020; final revision received September 17, 2020; accepted for publication October 7, 2020. Published online April 20, 2021.

Author contributions: Study concept: Qin, Owen. Data collection: Qin, Grogan, Szerlip, Chopra, Journey, Waninger, Green, Owen. Data analysis: Qin, Zhao, Wei, Green, Owen. Data review: Spakowicz. Patient treatment: Miah, Patel, Johns, Bertino, He, Shields, Kalemkerian, Gadgeel, Ramnath, Schneider, Hassan, Carbone, Presley, Otterson. Manuscript writing: Qin. Manuscript review: Zhao, Miah, Wei, Patel, Johns, Grogan, Bertino, He, Shields, Kalemkerian, Gadgeel, Ramnath, Schneider, Hassan, Szerlip, Chopra, Journey, Waninger, Spakowicz, Carbone, Presley, Otterson, Green, Owen.

Disclosures: Dr. Qin disclosed receiving personal fees from Boehringer Ingelheim, and grant/research support from Clovis, Merck, and Takeda. Dr. Bertino disclosed receiving personal fees from Boehringer Ingelheim and Takeda. Dr. He disclosed receiving personal fees from Perthera and Geneplus, and grant/research support from Bristol Myers Squibb, Mirati Therapeutics, Adaptimmune, and Genentech/Roche. Dr. Kalemkerian disclosed receiving grant/research support from Merck, GlaxoSmithKline, Takeda, and AbbVie. Dr. Gadgeel disclosed receiving nonfinancial support from AstraZeneca and Genentech/Roche; receiving personal fees from AbbVie, AstraZeneca, Bristol Myers Squibb, Genentech/Roche, Pfizer, and Takeda; receiving grant/research support from Merck, Blueprint Medicines, Aeglea Biotherapeutics, Astellas Pharma, G1 Therapeutics, Genentech/Roche, Lycera, Daiichi Sankyo, Pfizer, and Takeda; and serving as a scientific advisor for Merck, Genentech/Roche/AstraZeneca, and Bristol Myers Squibb. Dr. Ramnath disclosed receiving grant/research support from Merck and Clovis. Dr. Schneider disclosed receiving personal fees from Genentech/Roche, and grant/research support from Genentech/Roche, MedImmune, OncoMed, Bristol Myers Squibb, and Macrogenics. Dr. Carbone disclosed receiving grant/research support from Bristol Myers Squibb, and personal fees from AstraZeneca, Bayer, Biothera, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Genentech/Roche, Merck, Novartis, Peregrine Pharmaceuticals, Pfizer, Synta, Helsinn Therapeutics, AbbVie, Inivata, Loxo, Incyte, and Nexus Pharmaceuticals. Dr. Presley has disclosed being a Paul Calabresi Scholar supported by the Ohio State University K12 Training Grant for Clinical Faculty Investigators (5K12 CA133250-09) and the OSUCCC Pelotonia Junior Investigator Award. Dr. Otterson disclosed receiving grant/research support from Genentech/Roche, Bristol Myers Squibb, Clovis, Merck, Novartis, Pfizer, AstraZeneca, Acerta Pharma, and Ignyta; and personal fees from Novartis, Takeda, and Novocure. Dr. Owen disclosed receiving grant/research support from the Paul Calabresi Scholar program, Ohio State University K12 Training Grant for Clinical Faculty Investigators (5K12 CA133250-09), Genentech/Roche, Bristol Myers Squibb, Merck, Palobiofarma, and AbbVie; and personal fees from the Mednet and AstraZeneca. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this article was supported by the NCI of the NIH (number P30CA016058). This study was also supported by the Ohio State University Center for Clinical and Translational Science grant support (National Center for Advancing Translational Sciences, grant UL1TR002733).

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Correspondence: Angel Qin, MD, Division of Hematology and Oncology, University of Michigan, 1500 East Medical Center Drive, Med Inn-C353 SPC 5848, Ann Arbor, MI 48103. Email: qina@med.umich.edu

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