ROLE OF DENOSUMAB IN COMPARISON TO
ZOLEDRONIC ACID IN NSCLC WITH BONE METASTASIS
Presented by
Dr. Rajib BhattacharjeeIPGME&R and SSKM Hospital, Kolkata
CANCERS WITH SKELETAL METASTASIS
Predominantly osteolytic•Lung•Thyroid•Kidney•GI Tract•Melanoma
Predominantly osteosclerotic
•Prostate•Medulloblastoma•Carcinoids
Mixed•Breast
BACKGROUND Lung cancer is the leading cause of
cancer related deaths worldwide.
Smoking is the main etiological factor.
NSCLC is on the rise especially in never or light smokers. Adenocarcinoma is the common histology in such cases.
30-40% of cases present with skeletal metastasis.
APPROACHES TO BONE METASTASIS
Pain killers – NSAIDS, Opioids, Anti-convulsants, Anti-depressants.
Bisphosphonates – Alendronate, Pamidronate, Ibadronate, Zoledronic acid.
Monoclonal antibody – Denosumab
Palliative Irradiation – 8 Gy/1#, 20 Gy/5#, 30Gy/10#
Radiopharmaceuticals – Strontium-89, Samarium-153.
ZOLEDRONIC ACID
•Binds to bone minerals and inhibit hydroxyapetite dissolution.
•Inhibits osteoclast maturation.
•Promotes osteoclast apoptosis.
•Inhibits cytoskeletal organisation of osteoclast
•Direct antitumor effect.
•Prevents angiogenesis
DENOSUMAB
Binds to RANK-L
Inhibits OCL formation,function and survival
Prevents maturation of OCL
Decreases bone resorption
Breaks the vicious cycle of bone destruction
THE TWO AGENTS IN CONTENTION
DENOSUMAB
On November2010, FDA approved
Denosumab for prevention of skeletal related events(SRE) in patients with bone metastasis from solid tumors.
ZOLEDRONIC ACID
In February 2002, FDA approved zoledronic acid (4 mg) for the treatment of multiple myeloma and bone metastases secondary to a wide variety of solid tumors
REVIEW OF LITERATURE
DELAYS SRE !
SURVIVAL ADVANTAGE !!
STUDY
USEFULNESS OF DENOSUMAB TO NONSQUAMOUS NON-SMALL CELL LUNG CANCER PATIENTS WITH BONE METASTASES.
Hibiki Udagawa, Seiji Niho, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Kiyotaka Yoh, Hironobu Ohmatsu, Koichi Goto,
Dept. of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
Journal of Clinical Oncology, 2015 ASCO Annual Meeting.Vol 33, No 15_suppl (May 20 Supplement), 2015: 9609© 2015 American Society of Clinical Oncology
METHODS Type of study – Retrospective study
Study duration – May 2010 to April 2014
Selection criteria Age < 75 years Non squamous NSCLC with skeletal metastasis Treated with Platinum doublet or EGFR TKI as 1st line systemic therapy
STUDY END POINTS Overall survival (OS)
Progression free survival (PFS)
Time to SRE Pathological fracture Spinal cord compression Radiation or surgery to bone
STUDY SCHEMA
Eligible patientsNon squamous NSCLC
with bone mets(n=149)
Dmab group
Denosumab(n=52)
ZA group
Zoledronic acid(n=51)
Non-group
No treatment(n=46)
PRIOR RATE OF SRE
Series10.00%5.00%
10.00%15.00%20.00%25.00%30.00%35.00%40.00%45.00%50.00%
Dmab
ZA Non
44.2%
43.1%
21.7%
PFS IN PATIENTS TREATED WITH PLATINUM BASED CHEMOTHERAPY
Series10
1
2
3
4
5
6
Dmab ZA Non
5.1 mo
3.3 mo
4.3 mo
P = 0.046
OVERALL SURVIVAL
Series10
5
10
15
20
25
30
Non
25.4 mo
13.9 mo11.2 mo
Dmab
ZAP = 0.01
DENOSUMAB MAY IMPROVE OVERALL SURVIVAL COMPARED TO ZOLEDRONIC ACID OR NO TREATMENT IN PATIENTS WITH NON SQUAMOUS NSCLC WITH SKELETAL METASTASIS