İmmün kontrol noktası inhibitörü alan hastalarda kemik koruycu ajanların kullanımı ile sağ kalım arasındaki ilişki

Yıl 2025, Cilt: 6 Sayı: 4, 328 - 331, 31.08.2025

Onur Baş , Nesime İnci Güner , Mert Tokatlı , Naciye Güdük , Taha Koray Şahin , Nadir Yalçın , Sercan Aksoy

https://doi.org/10.47582/jompac.1650793

Öz

Giriş: Kemik metastazlarının yönetimi kanser hastaları için çok önemlidir. Bu çalışmanın amacı, immün kontrol noktası inhibitörleri (ICI) ile tedavi edilen hastalarda sağkalım sonuçları ile kemik koruyucu ajan (BMA) kullanımı arasındaki ilişkiyi değerlendirmektir.
Method: Bu çalışmaya, Ocak 2018 ile Aralık 2023 arasında en az 3 doz ICI alan ve ICI tedavisine başlanıldığı esnada kemik metastazı olan hastalar dahil edilmiştir. Hastalar ait olan kanser tipi, spesifik immünoterapi tedavisi ve aldıkları BMA'larla ilgili bilgiler de dahil olmak üzere bütün veriler retrospektif olarak hastane kayıt sisteminden elde edilmiştir.
Bulgular: 142 hasta çalışmaya dahil edilmiştir. Ortanca takip süresi 36 [Çeyrekler arası aralık (IQR)=18-50] ay ve BMA'ların başlanmasından son kontrole kadar olan ortanca takip süresi 14 aydı (IQR=5-29). Çok değişkenli analizlerde yaş, cinsiyet, ‘’Eastern Cooperative Oncology Group Scale ‘’(ECOG) skoru ve önceki tedavi sayısı için ayarlama yapıldığında, BMA kullanmayan hastalarda genel sağkalım süresinin daha kısa olduğu görülmüştür. (HR: 2.30, %95CI: 1.03-2.45; p=0.036). Ayrıca, BMA kullanımının 24 aya eşit veya daha uzun sağkalım olarak tanımlanan uzun dönem fayda ile ilişkili olduğu görülmüştür. (HR: 2.85, %95CI 1.13-7.21; p=0.027).
Sonuç: Kemik koruyucu ajanların kullanılmasının, ICI ile tedavi edilen ve kemik metastazı olan hastalarda genel sağkalımın bağımsız bir belirleyicisi olabileceği bulunmuştur. Bu bulgu, klinisyenleri kemik metastazları tespit edildikten sonra mümkün olan en kısa sürede BMA'lara başlamaya yönlendirebilir.

Anahtar Kelimeler

İmmün kontrol noktası inhibitörleri , denosumab , zoledronik asit , sağkalım , uzun dönem fayda

Bone-modifying agents and survival in patients treated with immune checkpoint inhibitors

Öz

Aims: Management of bone metastasis is crucial for cancer patients. The objective of this study was to assess the correlation between survival outcomes and bone-modifying agents (BMAs) in patients treated with immune checkpoint inhibitors (ICIs).
Methods: This study was conducted in individuals who received at least 3 doses of ICIs between January 2018 and December 2023 and had bone metastases at initiation of ICIs. We retrospectively collected data on each patient from their medical records, including information on cancer, the specific immunotherapy treatment, and the BMAs they were receiving.
Results: 142 patients were included. The median follow-up was 36 [interquartile range (IQR)=18-50] months and the median follow-up from the initiation of BMAs to the last control was 14 months (IQR=5-29). After adjustment for age, gender, Eastern Cooperative Oncology Group (ECOG) score and number of prior treatment lines in the multivariate analyses, patients who did not use BMAs had decreased overall survival (OS) (HR: 2.30, 95%CI: 1.03-2.45; p=0.036). In addition, BMAs use was associated with long-term benefit defined as having a survival of equal to or longer than 24 months (HR: 2.85, 95%CI 1.13-7.21; p=0.027).
Conclusion: It was found that using BMAs could be an independent predictor of OS in patients treated with ICI and who had bone metastasis. This finding may lead clinicians to start BMAs as soon as possible after bone metastases are detected.

Anahtar Kelimeler

Immune checkpoint inhibitors , denosumab , zoledronic acid , survival , long-term benefit

Kaynakça

• Hwang A, Mehra V, Chhetri J, Ali S, Tran M, Roddie C. Current treatment options for renal cell carcinoma: focus on cell-based immunotherapy. Cancers (Basel). 2024;16(6):1209. doi:10.3390/cancers16061209
• Knight A, Karapetyan L, Kirkwood JM. Immunotherapy in melanoma: recent advances and future directions. Cancers. 2023;15(4):1106. doi:10. 3390/cancers15041106
• Stanley R, Flanagan S, Reilly DO, Kearney E, Naidoo J, Dowling CM. Immunotherapy through the lens of non-small cell lung cancer. Cancers. 2023;15(11):2996. doi:10.3390/cancers15112996
• Jiang C, Wang S, Zhu L. Efficacy and safety of immunotherapy for head and neck squamous cell carcinoma: a meta-analysis of randomized clinical trials. Front Oncol. 2024;14:1489451. doi:10.3389/fonc.2024. 1489451
• Patel DM, Mateen R, Qaddour N, et al. A comprehensive review of immunotherapy clinical trials for metastatic urothelial carcinoma: immune checkpoint inhibitors alone or in combination, novel antibodies, cellular therapies, and vaccines. Cancers (Basel). 2024;16(2): 335. doi:10.3390/cancers16020335
• Ling SP, Ming LC, Dhaliwal JS, et al. Role of immunotherapy in the treatment of cancer: a systematic review. Cancers. 2022;14(21):5205. doi: 10.3390/cancers14215205
• Wang Y, Wang M, Wu HX, Xu RH. Advancing to the era of cancer immunotherapy. Cancer Communications (London, England). 2021; 41(9):803-829. doi:10.1002/cac2.12178
• Hendriks LE, Hermans BC, van den Beuken-van Everdingen MH, Hochstenbag MM, Dingemans AM. Effect of bisphosphonates, denosumab, and radioisotopes on bone pain and quality of life in patients with non-small cell lung cancer and bone metastases: a systematic review. J Thorac Oncol. 2016;11(2):155-173. doi:10.1016/j.jtho. 2015.10.001
• Hong S, Youk T, Lee SJ, Kim KM, Vajdic CM. Bone metastasis and skeletal-related events in patients with solid cancer: a Korean nationwide health insurance database study. PLoS One. 2020;15(7):e0234927. doi:10. 1371/journal.pone.0234927
• Yang M, Liu C, Yu X. Skeletal-related adverse events during bone metastasis of breast cancer: current status. Discov Med. 2019;27(149):211-220.
• Herget G, Saravi B, Schwarzkopf E, et al. Clinicopathologic characteristics, metastasis-free survival, and skeletal-related events in 628 patients with skeletal metastases in a tertiary orthopedic and trauma center. World J Surg Oncol. 2021;19(1):62. doi:10.1186/s12957-021-02169-7
• Saad F, Ivanescu C, Phung D, et al. Skeletal-related events significantly impact health-related quality of life in metastatic castration-resistant prostate cancer: data from PREVAIL and AFFIRM trials. Prostate Cancer Prostatic Dis. 2017;20(1):110-116. doi:10.1038/pcan.2016.62
• Costa L, Badia X, Chow E, Lipton A, Wardley A. Impact of skeletal complications on patients' quality of life, mobility, and functional independence. Support Care Cancer. 2008;16(8):879-89. doi:10.1007/s00520-008-0418-0
• Hamza FN, Mohammad KS. Immunotherapy in the battle against bone metastases: mechanisms and emerging treatments. Pharmaceuticals (Basel, Switzerland). 2024;17(12):1591. doi:10.3390/ph17121591
• Van Acker HH, Anguille S, Willemen Y, Smits EL, Van Tendeloo VF. Bisphosphonates for cancer treatment: mechanisms of action and lessons from clinical trials. Pharmacol Ther. 2016;158:24-40. doi:10.1016/ j.pharmthera.2015.11.008
• Ottewell PD, Brown HK, Jones M, et al. Combination therapy inhibits development and progression of mammary tumours in immunocompetent mice. Breast Cancer Res Treat. 2012;133(2):523-536. doi:10.1007/s10549-011-1782-x
• Tanaka Y, Iwasaki M, Murata-Hirai K, et al. Anti-tumor activity and immunotherapeutic potential of a bisphosphonate prodrug. Scientific Reports. 2017;7(1):5987. doi:10.1038/s41598-017-05553-0
• Zheng Y, Wang PP, Fu Y, Chen YY, Ding ZY. Zoledronic acid enhances the efficacy of immunotherapy in non-small cell lung cancer. Int Immunopharmacol. 2022;110:109030. doi:10.1016/j.intimp.2022.109030
• Sun D, Zhu H, Xu Q, et al. Comparative efficacy of bone-modifying agents in the treatment of lung cancer bone metastases: immunotherapy era. Future Oncol. 2025:1-11. doi:10.1080/14796694.2025.2525744
• Tamiya H, Nishino K, Kato Y, et al. Impact of bone-modifying agents on post-bone metastasis survival across cancer types. Curr Oncol. 2025; 32(1):42. doi:10.3390/curroncol32010042
• Chen Z, Shen Z, Wang X, et al. Combination of bone-modifying agents with immunotarget therapy for hepatocellular carcinoma with bone metastases. J Clin Med. 2022;11(23):6901. doi:10.3390/jcm11236901
• Liede A, Hernandez RK, Wade SW, et al. An observational study of concomitant immunotherapies and denosumab in patients with advanced melanoma or lung cancer. Oncoimmunology. 2018;7(12): e1480301. doi:10.1080/2162402x.2018.1480301
• LeVee A, Peluso E, Lechner MG, et al. Efficacy and immune-related adverse events of pembrolizumab with bone-modifying agents in female patients with breast cancer. Oncologist. 2025;30(6):oyaf134. doi:10.1093/oncolo/oyaf134
• Bongiovanni A, Foca F, Menis J, et al. Immune checkpoint inhibitors with or without bone-targeted therapy in NSCLC patients with bone metastases and prognostic significance of neutrophil-to-lymphocyte ratio. Front Immunol. 2021;12:697298. doi:10.3389/fimmu.2021.697298
• Wajda BG, Ferrie LE, Abbott AG, Elmi Assadzadeh G, Monument MJ, Kendal JK. Denosumab vs. zoledronic acid for metastatic bone disease: a comprehensive systematic review and meta-analysis of randomized controlled trials. Cancers (Basel). 2025;17(3):388. doi:10.3390/cancers 17030388