# Presentation: 893771

## Clinical Benefit of Bisphosphonates for Cancer Patients with Metastatic Bone Disease

**James R. Berenson, MD**
**Medical & Scientific Director**
**Institute for Myeloma & Bone Cancer Research**
**Los Angeles, California**

## Metastatic Bone Disease: Scope of the Problem

**Extremely common - > 500,000 patients in USA**
**Myeloma - > 90%**
**Breast - two thirds of patients**
**Prostate - two thirds of patients**
**Lung - one third of patients**
**Median survival measured in years, not weeks or months**
**Major clinical consequences for patients, families, and society**

## Clinical Consequences of Metastatic Bone Disease† 

**Pathologic fractures****	****10 - 25**
**Spinal cord compression/collapse****	****3 - 5**
**Radiation therapy****	****15 - 20**
**Surgery to bone****	****	****5 - 10**
**Hypercalcemia****	****2 - 10**
**Bone pain****	****50**
**Use of analgesics****	****40**
**Quality-of-life effects****	****	****	**
**Survival****	**

**% of patients/yr**

**SREs**

**SREs = Skeletal-related events.**
**† ****From PLAC arms of randomized clinical trials with Aredia****®**** or Zometa****®****.**

## IV Bisphosphonates—Major Impact in Reducing Skeletal Complications for Cancer Patients With Metastatic Bone Disease

|  |  % with SRE  |  |  | # SREs per yr |  |  |
| --- | --- | --- | --- | --- | --- | --- |
|  | Placebo | BP | %† | Placebo | BP | % |
| Prostate(Saad et al.) | 49        | Z-38 | 22* | 1.5 | 0.7 | 47* |
| Breast (Hortobagyi et al.)
(Kohno et al.) | 64 
50 | A-51 
Z-30 | 20* 
40* | 3.7 
1.42      | 2.4
0.7 | 35*
50* |
| Myeloma (Berenson et al.) | 51 | A-38 | 26* | 2.0 | 1.0 | 50* |
| Others(Rosen et al.) | 46 | Z-39 | 15 | 2.7 | 1.7 | 37* |

**SRE = Skeletal-related event; Pbo = Placebo; BP = Bisphosphonate; Z = Zometa****®****;**** A = Aredia****®****;**** ***** *****P *****< 0.05;   † Relative decrease**

## Breast Cancer and Multiple Myeloma Efficacy Summary† 

|  | Proportionwith SRE, % | Time to first SRE (median)‡ | Mean skeletal morbidity rate‡ | Multiple event analysis Hazard ratio‡ |
| --- | --- | --- | --- | --- |
| Zometa® 4 mg | 47 | 376 | 1.04 | 0.841 |
| Aredia® 90 mg | 51 | 356 | 1.39 | — |
| P value | .243 | .151 | .084 | .030 |

**†**** ****Rosen LS, et al.***** Cancer. *****2003;98:1735–1744.**
**‡ ****Hypercalcemia of malignancy (included as a skeletal-related event).**

## Benefits of IV Bisphosphonates in Metastatic Bone Disease

**Reduce skeletal complications**
**Aredia****®**
**Breast cancer and myeloma with lytic lesions**
**Ineffective in prostate cancer**
**Not tested in other tumor types**
**Zometa****®**
**Breast cancer, myeloma, and prostate cancer**
**Tested and effective in other tumor types**
**Decrease pain and analgesic use**
**Prevent deterioration of quality of life**

## ONJ in Myeloma Patients—The IMBCR Experience 

**6 cases of ONJ**
**Range of severity**
**3 patients required intermittent antibiotics (Aredia + Zometa, Zometa only in 2) - remain on bisphosphonate treatment **
**1 patient recently diagnosed with minor temporary discomfort (Aredia only) - remains on treatment**
**Largely resolved with clarithromycin PO**
**2 patients (Aredia + Zometa,  Zometa only) discontinued bisphosphonate secondary to significant effect on mastication**
**Status of myeloma**
**3 in long-term complete remission (auto-PSCT, VAD, thalidomide)**
**1 in near complete remission (on steroids) **
**2 with long-term indolent myeloma requiring ****no other therapy **
**1 patient with 40% reduction in M-protein for > 4 yr**

## Perspective—IV Bisphosphonates in Cancer Patients with Bone Involvement

**Skeletal complications have profound effects on the lives of patients with metastatic bone disease**
**IV bisphosphonate (Zometa****®**** and Aredia****®****) **
**Reduce bony complications**
**Number of events/yr one third to one half**
**Percent of patients with events by 15% to 40%**
**Decrease bone pain, reduce pain meds, and prevent deterioration in QOL**

## Perspective—IV Bisphosphonates in Cancer Patients with Bone Involvement

**Patients receiving IV bisphosphonates ****(Zometa and Aredia)**
**Infrequently develop any form of ONJ ****(0.1% to 2%/yr) **
**Severity varies; most patients improve while continuing bisphosphonate therapy**
**ONJ risk minor - rarely clinically significant compared with major problems that frequently occur without Aredia or Zometa treatment (eg, fractures, spinal cord compression, radiation therapy, or surgery)**

## IV Bisphosphonates for Patients With Metastatic Bone Disease—Benefits vs Risks

**Benefits****	****Risks**

**Fractures **
**Radiotherapy**
**Bone pain**

**ONJ ? **
**Renal ****(infrequent)**

**Humeral fracture in ****a myeloma patient**