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