# Presentation: 663528

## Bisphosphonate Bone Metastases TrialsProportion of Patients With Any SRE§(12, 010)

**	****	****	****              ****Patients, %**
**Treatment****	****N ****	****3 mo****	****6 mo****	****9 mo****	****12 mo**
**Pamidronate Study 12**
**   ****Pam 90 mg****	****198****	****10****	****21****	****24****	****28**
**   ****Placebo****	****179****	****21****	****32****	****41****	****44**
**ZOMETA****®**** Study 010**
**   ****ZOMETA 4 mg****	****183****	****31****	****38****	****40****	****47**
**   ****ZOMETA 8/4 mg****	****160****	****31****	****39****	****45****	****49**
**   ****Pam 90 mg****	****167****	****25****	****40****	****45****	****49**

**42**

**§Intent-to treat.**

## Bisphosphonate Bone Metastases Trials Demographic and Prognostic Variables(12, 010) 

**                 ****Pamidronate Study 12****	****                          ZOMETA****®**** Study 010**
**	****	****Pam****	****	****ZOMETA****	****ZOMETA ****	****Pam ****	****	****90 mg****	****Placebo****	****4 mg****	****8/4 mg ****	****90 mg****	**** Variable ****	****N = 198****	****N = 179****	****N = 183****	****N = 160****	****N = 167**
**Age, yr****	****Mean ± s.d.****	****64.1 ± 9.4****	****62.7 ± 10.1****	****63.1 ± 10.52****	****62.2 ± 11.37****	****62.6 ± 11.41****	****Median****	****66.0****	****63.0****	****62.0****	****63.0****	****62.0**
**Time from initial****diagnosis to Visit 2, mo****   Mean ± s.d.****	****30.5 ± 32.2****	****27.7 ± 33.5****	****18.0 ± 32.24****	****13.5 ± 21.75****	****17.3 ± 28.62****	****Median****	****19.3****	****14.4****	****2.8****	****2.6****	****2.7**
**	**

**42**

## Bisphosphonate Bone Metastases Trials Proportion of Patients With Pathologic Fractures§(12, 010)

**Pamidronate Study 12:****Proportion of patients with pathologic fracture in the 3 mo prior to study entry**
**Time from diagnosis****	****	****Without pathologic****	****With pathologic****to study entry****	****N****	****fractures, %****	****fractures, %**
****** ****6 mo****	****115****	****75****	****25**
**> 6 mo****	****277****	****90****	****10**

**ZOMETA****®**** Study 010: Proportion of pamidronate patients with pathologic fracture**
**Time from diagnosis****	****	****	****                        Patients, %****	****	****to study entry****	****N****	****3 mo****	****6 mo****	****9 mo****	****13 mo**
****** ****6 mo****	****104****	****21****	****38****	****40****	****45**
**> 6 mo****	****  62****	****15****	****24****	****32****	****37**

**42**

**§Intent-to treat.**

## Patients With Any SRE up to End-of-Core by Race (010, 011, 039)

**	****	****	****	****Patients, n/N (%)               **
**Study****	****	****ZOMETA****®**** ****	****ZOMETA****	****Pam 90 mg/ ****	****number****	****Race****	****4 mg****	****8/4 mg****	****placebo ****	**

**010****	****	****N = 561****	****N = 524****	****N = 555**
**	****White****	****225/493 (46)****	****206/443 (47)****	****234/484 (48)**
**	****Black****	****10/34 (29)****	****22/42 (52)****	****13/43 (30)**
**	****Other****	****13/34 (38)****	****14/39 (36)****	****10/28 (36)**
**011****	****	****N = 257****	****N = 266****	****N = 250**
**	****White****	****91/229 (40)****	****85/238 (36)****	****103/226 (46)**
**	****Black****	****4/15 (27)****	****4/15 (27)****	****4/12 (33)**
**	****Other****	****2/13 (15)****	****3/13 (23)****	****4/12 (33)**
**039****	****	****N = 214****	****N = 221****	****N = 208**
**	****White****	****64/178 (36)****	****69/186 (37)****	****77/172 (45)**
**	****Black****	****4/24 (17)****	****7/19 (37)****	****8/19 (42)**
**	****Other****	****3/12 (25)****	****9/16 (56)****	****7/17 (41)**

**54**

## ZOMETA® Efficacy in Bone Metastases

**ZOMETA****®**** Efficacy in Bone Metastases**

**Prostate cancer**
**(039)**

**Solid tumors****–PC/BC****(011)**

**Breast cancer and**
**multiple myeloma**
**(010)**

**N = **

**214**

**221**

**208**

**257**

**266**

**250**

**564**

**526**

**558**

**29**

**HCM**
**(036, 037)**

**44**

**42**

**36**

## Solid Tumors – PC/BCAntineoplastic Therapies After Start of Study Drug (011)

**	****	****	****Patients, n (%)              **
**	****	****ZOMETA****®****	****ZOMETA****	****	**
**	****	****4 mg****	****8/4 mg****	****Placebo **
**Antineoplastic therapy ****	****N = 254****	****N = 265****	****N = 247**

**37**

**Any****	****192****	****(75.6)****	****184****	****(69.4)****	****181****	****(73.3)**
**Carboplatin****	****74****	****(29.1)****	****58****	****(21.9)****	****65****	****(26.3)**
**Paclitaxel****	****52****	****(20.5)****	****58****	****(21.9)****	****46****	****(18.6)**
**Gemcitabine hydrochloride****	****39****	****(15.4)****	****28****	****(10.6)****	****25****	****(10.1)**
**Cisplatin****	****37****	****(14.6)****	****46****	****(17.4)****	****41****	****(16.6)**

- PTT 8.2-4

## Breast Cancer and Multiple MyelomaFrequency Distribution of Antineoplastic Regimens (010) (1)

**	****	****	****	****Patients, n (%)              **
**	****	****	****ZOMETA****®****	****ZOMETA****	****Pam****	**
**	****	****No. of ****	****4 mg****	****8/4 mg****	****90 mg **
**Stratum****	****regimen****	****N = 563****	****N = 524****	****N = 556**

**37**

**Multiple myeloma, n****	****   ****	****                186****	****                      160****	****               167**
**	****	****   ****0****	****11****	****(5.9)****	****10****	****(6.3)****	****11****	****(6.6)**
**	****	****   ****1****	****74****	****(39.8)****	****58****	****(36.3)****	****72****	****(43.1)**
**	****	****   ****2****	****43****	****(23.1)****	****43****	****(26.9)****	****41****	****(24.6)**
**	****	****   ****3****	****29****	****(15.6)****	****31****	****(19.4)****	****21****	****(12.6)**
**	****	****   ****4****	****17****	****(9.1)****	****11****	****(6.9)****	****12****	****(7.2)**
**	****	******** ****5****	****12****	****(6.5)****	****7****	****(4.4)****	****10****	****(6.0)****	**

- PTT 8.2-7

## Breast Cancer and Multiple MyelomaFrequency Distribution of Antineoplastic Regimens (010) (2)

**	****	****	****	****Patients, n (%)              **
**	****	****	****ZOMETA****®****	****ZOMETA****	****Pam****	**
**	****	****No. of ****	****4 mg****	****8/4 mg****	****90 mg **
**Stratum****	****regimen****	****N = 563****	****N = 524****	****N = 556**

**37**

**Breast cancer with ****	****    **
**chemotherapy, n ****	****	****                    176****	****                    169****	****                 179   **
**	****	****   ****0****	****3****	****(1.7)****	****5****	****(3.0)****	****6****	****(3.4)**
**	****	****   ****1****	****53****	****(30.1)****	****51****	****(30.2)****	****58****	****(32.4)**
**	****	****   ****2****	****61****	****(34.7)****	****65****	****(38.5)****	****56****	****(31.3)**
**	****	****   ****3****	****34****	****(19.3)****	****22****	****(13.0)****	****35****	****(19.6)**
**	****	****   ****4****	****11****	****(6.3)****	****17****	****(10.1)****	****16****	****(8.9)**
**	****	******** ****5****	****14****	****(8.0)****	****9****	****(5.3)****	****8****	****(4.5)**
**Breast cancer with****	**
**hormonal therapy, n****	****	****                    201 ****	****                   195  ****	****                210   **
**	****	****   ****0****	****3****	****(1.5)****	****1****	****(0.5)****	****3****	****(1.4)**
**	****	****   ****1****	****93****	****(46.3)****	****114****	****(58.5)****	****91****	****(43.3)**
**	****	****   ****2****	****59****	****(29.4)****	****48****	****(24.6)****	****69****	****(32.9)**
**	****	****   ****3****	****32****	****(15.9)****	****19****	****(9.7)****	****34****	****(16.2)**
**	****	****   ****4****	****7****	****(3.5)****	****7****	****(3.6)****	****8****	****(3.8)**
**	****	******** ****5****	****7****	****(3.5)****	****6****	****(3.1)****	****5****	****(2.4)****	**

- PTT 8.2-7

## Solid Tumors – PC/BCFrequency Distribution of Antineoplastic Regimens (011)

**	****	****	****	****Patients, n (%)              **
**	****	****	****ZOMETA****®****	****ZOMETA****	****	**
**	****	****No. of ****	****4 mg****	****8/4 mg****	****Placebo **
**Stratum****	****regimen****	****N = 254****	****N = 265****	****N = 247**

**37**

**Non small cell lung cancer, n ****	**** ****	****                     120    ****	****                  130****	****                    117**
**	****	****   ****0****	****20****	****(16.7)****	****29****	****(22.3)****	****25****	****(21.4)**
**	****	****   ****1****	****50****	****(41.7)****	****65****	****(50.0)****	****67****	****(57.3)**
**	****	****   ****2****	****36****	****(30.0)****	****24****	****(18.5)****	****16****	****(13.7)**
**	****	****   ****3****	****9****	****(7.5)****	****6****	****(4.6)****	****5****	****(4.3)**
**	****	****   ****4****	****5****	****(4.2)****	****3****	****(2.3)****	****3****	****(2.6)**
**	****	******** ****5****	****0****	****(0)****	****3****	****(2.3)****	****1****	****(0.9)**
**Other solid tumors, n****	****	****                      134****	****                       135  ****	****                 130    **
**	****	****   ****0****	****42****	****(31.3)****	****52****	****(38.5)****	****41****	****(31.5)**
**	****	****   ****1****	****61****	****(45.5)****	****60****	****(44.4)****	****54****	****(41.5)**
**	****	****   ****2****	****22****	****(16.4)****	****17****	****(12.6)****	****29****	****(22.3)**
**	****	****   ****3****	****8****	****(6.0)****	****3****	****(2.2)****	****4****	****(3.1)**
**	****	****   ****4****	****1****	****(0.7)****	****3****	****(2.2)****	****1****	****(0.8)**
**	****	******** ****5****	****0****	****(0)****	****0****	****(0)****	****1****	****(0.8)**

- PTT 8.2-7

## Solid Tumors –PC/BCTime to First SREDeaths and Dropouts Considered SREs (011) 

**	****	****Median time,****	*****P*****-value ****	****N (%)****§**** ****	****days****	****vs placebo**
**ZOMETA****®**** 4 mg****	****257 (73)****	****127****	****.006 **
**ZOMETA 8/4 mg****	****266 (80)****	****105****	****.184**
**Placebo****	****250 (82)****	****85**

**§Kaplan-Meier estimate of the proportion at Month 9.**

## Breast Cancer and Multiple Myeloma Time to First SREDeaths and Dropouts Considered SREs (010) 

**	****	****Median time,****	*****P*****-value ****	****N (%)****§**** ****	****days****	****vs Pam 90 mg**
**ZOMETA****®**** 4 mg****	****561 (58)****	****312****	****.099 **
**ZOMETA 8/4 mg****	****555 (59)****	****265****	****.545**
**Pam 90 mg****	****524 (61)****	****252**

**§Kaplan-Meier estimate of the proportion at Month 13.**

## Prostate Cancer Time to First SREDeaths and Dropouts Considered SREs (039) 

**	****	****Median time, ****	*****P*****-value ****	****N (%)****§**** ****	****days****	****vs placebo**
**ZOMETA****®**** 4 mg****	****214 (66)****	****337****	****.030 **
**ZOMETA 8/4 mg****	****221 (74)****	****195****	****.924**
**Placebo****	****208 (73)****	****221**

**§Kaplan-Meier estimate of the proportion at Month 15.**

## Cumulative Incidence Rate of SREAll Patients§ (039)

**ZOMETA 4 mg****	****214****	****180****	****149****	****113****	****97****	****85****	****70****	****45**
**ZOMETA 8/4 mg****	****221****	****177****	****132****	****102****	****77****	****61****	****46****	****34**
**Placebo****	****208****	****171****	****128****	****103****	****78****	****64****	****43****	****31**

**	****                   ****Median time, days**
**ZOMETA****®**** 4 mg ****	****NR****	*****P***** = .013**
**ZOMETA 8/4 mg****	****NR****	*****P***** = .357**
**Placebo****	****337**

- 039 PTF 9.2-52p3

**21**

**§Intent-to-treat.**
**NR = Not reached.**

## Prostate CancerMedian Serum PSA Level (Observed) (039)

**ZOMETA 4 mg****	****212****	****150****	****162****	****132****	****85****	****102****	****90****	****60****	****67**
**ZOMETA 8/4 mg****	****218****	****158****	****156****	****146****	****69****	****106****	****74****	****45****	****53**
**Placebo****	****200****	****145****	****152****	****139****	****72****	****102****	****77****	****49****	****51**

**ZOMETA® 4 mg         ZOMETA 8/4 mg****	****         Placebo**

- 039 PTF 9.2-56

**54**

## Prostate CancerTotal Number of SREs (039)

**	****	****                  ****With 21-day window****	****       Without 21-day window**
**	****	****ZOMETA****®**** ****	****	****ZOMETA****	****	****	****	****4 mg****	**** Placebo****	****4 mg****	****Placebo**
**SRE (+HCM)****	****112****	****155****	****167****	****258**
**SRE****	****112****	****155****	****167****	****256**
**Pathologic fracture****	****  34****	**** 54****	****46****	****84**
**	****Vertebral fracture****	****  10****	**** 20****	****10****	****30**
**	****Nonvertebral fracture****	****  25****	**** 38****	****36****	****54**
**Radiation to bone****	****  65****	**** 85****	****90****	****130**
**Surgery to bone****	****    5****	****    8****	****5****	****8**
**Spinal cord compression****	****  10****	**** 15****	****13****	****17**
**Change to antineoplastic****	****therapy****	****  13****	**** 17****	****13****	****17**
**Hypercalcemia****	****    0****	**** 2****	****0****	****2**

**56**

**Pro 011 PTT 9.2-6xx**

## Cumulative Incidence Rate of SREAll Patients§ (011)

**ZOMETA 4 mg****	****257****	****173****	****107****	****62****	****46**
**ZOMETA 8/4 mg****	****266****	****177****	****99****	****56****	****40**
**Placebo****	****250****	****152****	****81****	****48****	****36**

**	****                  ****Median time, days**
**ZOMETA® 4 mg****	****314****	*****P***** = .044**
**ZOMETA 8/4 mg****	****NR****	*****P***** = .037**
**Placebo****	****185**

- 011 PTF 9.2-52p3

**20**

**§Intent-to-treat.**
**NR = not reached.**

## Solid Tumors –PC/BCTotal Number of SREs (011)

**	****	****                  ****With 21-day window****	****       Without 21-day window**
**	****	****ZOMETA****®**** ****	****	****ZOMETA****	****	****	****	****4 mg****	**** Placebo****	****4 mg****	****Placebo**
**SRE (+HCM)****	****131****	****163****	****201****	****275**
**SRE****	****131****	****156****	****201****	****267**
**Pathologic fracture****	****  48****	**** 63****	****  69****	****  95**
**	****Vertebral fracture****	****  21****	**** 32****	****  27****	****  41**
**	****Nonvertebral fracture****	****  31****	**** 34****	****  42****	****  54**
**Radiation to bone****	****  79****	****  101****	****112****	****153**
**Surgery to bone****	****  12****	****     9****	****  12****	****    9**
**Spinal cord compression****	****    7****	****    10****	****    8****	****  10**
**Hypercalcemia****	****    0****	****      8****	****    0****	****    8**

**56**

**Pro 011 PTT 9.2-6xx**

## Breast Cancer and Multiple MyelomaTotal Number of SREs (010)

**	****	****                  ****With 21-day window****	****       Without 21-day window**
**	****	****ZOMETA****®**** ****	****Pam****	****ZOMETA****	****Pam****	****	****	****4 mg****	**** 90 mg****	****4 mg****	****90 mg**
**SRE (+HCM)****	****411****	****451****	****808****	****849**
**SRE****	****408****	****440****	****801****	****835**
**Pathologic fracture****	****301****	****292****	****622****	****584**
**	****Vertebral fracture****	****131****	****133****	****202****	****214**
**	****Nonvertebral fracture****	****206****	****198****	****420****	****370**
**Radiation to bone****	****105****	****143****	****141****	****196**
**Surgery to bone****	****  23****	**** 36****	****  25****	****  37**
**Spinal cord compression****	****  12****	**** 16****	****  13****	****  18**
**Hypercalcemia****	****    7****	**** 14****	****    7****	****  14**

**56**

**Pro 011 PTT 9.2-6xx**