Top

memo - Magazine of European Medical Oncology

Published in:

01-06-2013 | original report

CECOG experts’ recommendations on the use of denosumab in the prevention of skeletal-related events in bone metastases of lung cancer

Authors: Wolfgang Hilbe, MD, Ufuk Abacioglu, MD, Daniel M. Aebersold, MD, Mounir Bachouchi, MD, Thomas Brodowicz, MD, Prof Rabab Gaafar, MD, Gerold Holzer, MD, Andrea Mohn-Staudner, MD, Dimitar Kalev, MD, Ewa Kalinka-Warzocha, MD, Viljem Kovac, MD, Marco Siano, MD, Fulden Yumuk, MD, Lilla Tamasi, MD

Published in: memo - Magazine of European Medical Oncology | Issue 2/2013

Abstract

Purpose

Skeletal-related events represent a substantial burden for patients with advanced cancer. Randomized, controlled studies suggested superiority of denosumab over zoledronic acid in the prevention of skeletal-related events in metastatic cancer patients, with a favorable safety profile. Experts gathered at the 2012 Skeletal Care Academy in Istanbul to bring forward practical recommendations, based on current evidence, for the use of denosumab in patients with bone metastases of lung cancer.

Recommendations

Based on current evidence, use of denosumab in lung cancer patients with confirmed bone metastases is recommended. It is important to note that clinical judgment should take into consideration the patient’s general performance status, overall prognosis, and live expectancy. Currently, the adverse event profile reported for denosumab includes hypocalcemia and infrequent occurrence of osteonecrosis of the jaw. Therefore, routine calcium and vitamin D supplementation, along with dental examination prior to denosumab initiation are recommended. There is no evidence for renal function impairment due to denosumab administration. At present, there is no rationale to discourage concomitant use of denosumab and surgery or radiotherapy.

Siegel R, Naishadham D, Jemal A. Cancer statistics. 2012. CA Cancer J Clin. 2012;62(1):10–29.PubMedCrossRef

Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220–41.PubMedCrossRef

Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, et al. SEER Cancer Statistics Review, 1975–2008, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER data submission, posted to the SEER web site. 2011. Accessed 2 Jan 2013.

Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12(20 Pt 2):6243s–9.PubMedCrossRef

Sugiura H, Yamada K, Sugiura T, Hida T, Mitsudomi T. Predictors of survival in patients with bone metastasis of lung cancer. Clin Orthop Relat Res. 2008;466(3):729–36.PubMedCrossRef

Tsuya A, Kurata T, Tamura K, Fukuoka M. Skeletal metastases in non-small cell lung cancer: a retrospective study. Lung Cancer. 2007;57(2):229–32.PubMedCrossRef

Rosen LS, Gordon D, Tchekmedyian NS, Yanagihara R, Hirsh V, Krzakowski M, et al. Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with non-small cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind, placebo-controlled trial. Cancer. 2004;100(12):2613–21.PubMedCrossRef

Sekine I, Nokihara H, Yamamoto N, Kunitoh H, Ohe Y, Tamura T. Risk factors for skeletal-related events in patients with non-small cell lung cancer treated by chemotherapy. Lung Cancer. 2009;65(2):219–22.PubMedCrossRef

Oefelein MG, Ricchiuti V, Conrad W, Resnick MI. Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol. 2002;168(3):1005–7.PubMedCrossRef

10.

Rosen LS, Gordon D, Tchekmedyian S, Yanagihara R, Hirsh V, Krzakowski M, et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial–the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol. 2003;21(16):3150–7.PubMedCrossRef

11.

EMA. 2011 [January 2]; Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002173/WC500110381.pdf. Accessed 2 Jan 2013.

12.

FDA. 2010 [January 2]; Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/125320s007lbl.pdf. Accessed 2 Jan 2013.

13.

Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011;29(9):1125–32.PubMedCrossRef

14.

Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ, Manegold C, et al. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol. 2012;7(12):1823–9.PubMedCrossRef

15.

Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E, et al. Metastatic non-small cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii56–64.PubMedCrossRef

16.

Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010;28(35):5132–9.PubMedCrossRef

17.

Fizazi K, Carducci M, Smith M, Damiao R, Brown J, Karsh L, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomized, double-blind study. Lancet. 2011;377(9768):813–22.PubMedCrossRef

18.

Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomized, phase 3 trials. Eur J Cancer. 2012;48(16):3082–92.PubMedCrossRef

19.

Roodman GD. Mechanisms of bone metastasis. N Engl J Med. 2004;350(16):1655–64.PubMedCrossRef

20.

Kitazawa S, Kitazawa R. RANK ligand is a prerequisite for cancer-associated osteolytic lesions. J Pathol. 2002;198(2):228–36.PubMedCrossRef

21.

Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2(8):584–93.PubMedCrossRef

22.

Feeley BT, Liu NQ, Conduah AH, Krenek L, Roth K, Dougall WC, et al. Mixed metastatic lung cancer lesions in bone are inhibited by noggin overexpression and Rank:Fc administration. J Bone Miner Res. 2006;21(10):1571–80.PubMedCrossRef

23.

Jones DH, Nakashima T, Sanchez OH, Kozieradzki I, Komarova SV, Sarosi I, et al. Regulation of cancer cell migration and bone metastasis by RANKL. Nature. 2006; 440(7084):692–6.PubMedCrossRef

24.

Miller RE, Roudier M, Jones J, Armstrong A, Canon J, Dougall WC. RANK ligand inhibition plus docetaxel improves survival and reduces tumor burden in a murine model of prostate cancer bone metastasis. Mol Cancer Ther. 2008;7(7):2160–9.PubMedCrossRef

25.

Miller R, Jones J, Roudier M, Dougall WC. The RANKL inhibitor OPG-Fc, either alone or in combination with docetaxel, blocks lung cancer-induced osteolytic lesions and reduces skeletal tumor burden in a murine model of non-small cell lung cancer in bone. 9th International Conference on Cancer-Induced Bone Disease;2009; Arlington, VA.

26.

Stahel RA, Peters S. ETOP Newsletter October 2012. 2012 [January 17]; Available from: http://www.etop-eu.org.

27.

Saad F, Brown JE, Van Poznak C, Ibrahim T, Stemmer SM, Stopeck AT, et al. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol. 2012; 23(5):1341–7.PubMedCrossRef

28.

AAOMS. Position Paper on Bisphosphonate-Related Osteonecrosis of the Jaw—2009 Update. 2009 [January 2]; Available from: http://www.aaoms.org/docs/position_papers/bronj_update.pdf.

29.

Lutz S, Berk L, Chang E, Chow E, Hahn C, Hoskin P, et al. Palliative radiotherapy for bone metastases: an ASTRO evidence-based guideline. Int J Radiat Oncol Biol Phys. 2011;79(4):965–76.PubMedCrossRef

30.

Chow E, Harris K, Fan G, Tsao M, Sze WM. Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol. 2007;25(11):1423–36.PubMedCrossRef

31.

Agarawal JP, Swangsilpa T, van der Linden Y, Rades D, Jeremic B, Hoskin PJ. The role of external beam radiotherapy in the management of bone metastases. Clin Oncol (R Coll Radiol). 2006;18(10):747–60.CrossRef

32.

Hall WA, Stapleford LJ, Hadjipanayis CG, Curran WJ, Crocker I, Shu HK. Stereotactic body radiosurgery for spinal metastatic disease: an evidence-based review. Int J of Surg Oncol. 2011; 2011:979214.

33.

Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009; 361(8):756–65.PubMedCrossRef

34.

Fizazi K, Brown JE, Carducci M, Shore ND, Sieber P, Kueppers F, et al. editors. Denosumab in patients with metastatic prostate cancer previously treated with denosumab or zoledronic acid: 2-year open-label extension phase results from the pivotal phase 3 study. European Society of Medical Oncology;2012.

35.

Stopeck AT, Lipton A, Martàn M, Body J-J, Paterson A, Steger GG, et al. editors. Denosumab in Patients with Breast Cancer and Bone Metastases Previously Treated with Zoledronic Acid or Denosumab: Results from the 2-Year Open-Label Extension Treatment Phase of a Pivotal Phase 3 Study. San Antonio Breast Cancer Symposium;2011.

Title: CECOG experts’ recommendations on the use of denosumab in the prevention of skeletal-related events in bone metastases of lung cancer
Authors: Wolfgang Hilbe, MD
Ufuk Abacioglu, MD
Daniel M. Aebersold, MD
Mounir Bachouchi, MD
Thomas Brodowicz, MD
Prof Rabab Gaafar, MD
Gerold Holzer, MD
Andrea Mohn-Staudner, MD
Dimitar Kalev, MD
Ewa Kalinka-Warzocha, MD
Viljem Kovac, MD
Marco Siano, MD
Fulden Yumuk, MD
Lilla Tamasi, MD
Publication date: 01-06-2013
Publisher: Springer Vienna
Published in: memo - Magazine of European Medical Oncology / Issue 2/2013
Print ISSN: 1865-5041
Electronic ISSN: 1865-5076
DOI: https://doi.org/10.1007/s12254-013-0088-6

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Recommendations

Please log in to get access to this content

Other articles of this Issue 2/2013

Single-agent bevacizumab as maintenance therapy in metastatic colorectal cancer: how long do we have to continue?

Optimal surveillance strategy of localised testicular non-germ cell sex-cord stromal tumours

Six years of MEMO: readers survey 2012

Lenalidomide induced response in a patient with follicular lymphoma of the skin and an anti-rituximab-antibody

The role of maintenance strategies in lymphoma and CLL

Local therapy in prostate cancer—surgery versus radiation

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Six years of MEMO: readers survey 2012 

The role of maintenance strategies in lymphoma and CLL 