Trends in use of intravenous bisphosphonates in patients with prostate cancer and newly diagnosed metastases to bone in two large U.S. integrated health systems.

192 Background: Bone is a common site of metastatic involvement in patients (pts) with prostate cancer (PC). Bony metastases (mets) are associated with skeletal complications, which can cause significant morbidity and mortality. Intravenous bisphosphonates (IV BPs) have been proven to reduce the incidence and onset of skeletal complications. Patterns of use of IV BPs in clinical practice in pts with bone mets due to PC are largely unknown. Methods: Using the tumor registries and electronic data stores at two large US integrated health systems that serve a total of approximately 1.3 million persons, we retrospectively identified all pts aged ≥18 yrs with primary PC and newly diagnosed bone mets between 1/1/95 and 12/31/09. Information on all administrations of IV BPs between date of diagnosis of bone mets and death, loss to follow-up, or end of study was extracted from administrative data stores and electronic medical records, which also were reviewed by trained medical abstractors for evidence of skeletal-related events (SREs) (spinal cord compression, pathologic fracture, surgery to bone, radiation to bone). Results: We identified a total of 461 pts with primary PC and newly diagnosed bone mets. Mean (SD) age was 72.8 yrs (10.7 yrs); 75% were Caucasian, and 21% were African-American. Median duration of follow-up after diagnosis of bone mets was 1.3 yrs. One-fifth (20.2%) of study subjects received IV BPs (92% zoledronic acid, 8% pamidronate) during follow-up--10.8% prior to, and 9.3% after, first on-study SRE. Median time from diagnosis of bone mets to first administration of IV BPs was 1.7 yrs, and the median number of administrations was 3. The percentage of study subjects receiving IV BPs increased steadily over the 15-yr study period--from 7.5% among those newly diagnosed with bone mets in 1995-1999, to 19.8% among those newly diagnosed with bone mets in 2000-2004, to 27.5% among those newly diagnosed with bone mets in 2005-2009. Conclusions: Despite a high risk of SREs in pts with PC and bone mets, most such pts still do not receive IV BPs.

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Risk of skeletal-related events (SREs) in patients with prostate cancer (PC) and newly diagnosed metastases to bone.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15197 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15197-e15197

Author(s):

Andrew Glass ◽

Lois Lamerato ◽

John Edelsberg ◽

Kathryn E. Richert-Boe ◽

Charu Taneja ◽

...

Keyword(s):

Clinical Practice ◽

Cumulative Incidence ◽

Randomized Clinical Trials ◽

Pathologic Fracture ◽

Cord Compression ◽

Routine Clinical Practice ◽

Initial Diagnosis ◽

Newly Diagnosed ◽

Risk Of Death

e15197 Background: Bone is a common site of metastatic involvement in patients (pts) with PC. Bony metastases (mets) are often associated with SREs (spinal cord compression [SCC], pathologic fracture [PF], surgery to bone [SB], radiotherapy to bone [RT]). Skeletal complications cause significant morbidity and mortality. Current estimates of SRE risk come principally from randomized clinical trials. Information from routine clinical practice is limited. Methods: Using the tumor registry and electronic data stores at a large U.S. Midwest healthcare system that serves approximately 800,000 persons, we retrospectively identified all pts aged ≥18 yrs with primary PC and newly diagnosed bone mets between 1/1/95 and 12/31/09. Electronic medical records were reviewed by trained abstractors for evidence of SREs between date of bone mets diagnosis and death, loss to follow-up, or end of study for evidence of first SRE. Cumulative incidence of SREs was estimated in the presence of competing risk of death. Results: We identified a total of 420 men with primary PC and newly diagnosed bone mets; 42 pts had evidence of SREs at initial diagnosis of bone mets and were excluded from the analyses. Among the remaining 378 pts, mean (SD) age was 72.7 yrs (9.8 yrs); 38% were Caucasian and 58% were African-American. Median duration of follow-up after diagnosis of bone mets was 17.1 months (mos). At 12 mos, cumulative incidence of SREs was 31.6% (SCC, 6.1%; PF, 15.0%; SCC and/or PF, 19.1%; SB, 3.9%; RT, 24.4%) (Table). Corresponding figures at 24 mos were 45.3% (SCC, 12.5%; PF, 22.2%; SCC and/or PF, 30.2%; SB, 6.2%; RT, 34.9%). Relatively few pts (14.6%) received intravenous bisphosphonates prior to SRE. Conclusions: Pts with PC in routine clinical practice are at high risk of SREs following initial diagnosis of bone mets. [Table: see text]

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Risk of skeletal-related events (SREs) in patients with breast cancer (BC) and newly diagnosed metastases to bone.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e12024 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e12024-e12024

Author(s):

Charu Taneja ◽

Lois Lamerato ◽

Andrew Glass ◽

Kathryn E. Richert-Boe ◽

John Edelsberg ◽

...

Keyword(s):

Clinical Practice ◽

Cumulative Incidence ◽

Randomized Clinical Trials ◽

Pathologic Fracture ◽

Cord Compression ◽

Routine Clinical Practice ◽

Initial Diagnosis ◽

Newly Diagnosed ◽

Risk Of Death

e12024 Background: Bone is a common site of metastatic involvement in patients (pts) with BC. Bony metastases (mets) are often associated with SREs (spinal cord compression [SCC], pathologic fracture [PF], surgery to bone [SB], radiotherapy to bone [RT]). Skeletal complications cause significant morbidity and mortality. Current estimates of SRE risk come principally from randomized clinical trials. Information from routine clinical practice is limited. Methods: Using the tumor registry and electronic data stores at a large US Midwest healthcare system that serves approximately 800,000 persons, we retrospectively identified all pts aged ≥18 yrs with primary BC and newly diagnosed bone mets between 1/1/95 and 12/31/09. Electronic medical records were reviewed by trained abstractors for evidence of SREs between date of bone mets diagnosis and death, loss to follow-up, or end of study. Cumulative incidence of SREs was estimated in the presence of competing risk of death. Results: We identified a total of 378 pts with primary BC and newly diagnosed bone mets; 87 pts had evidence of SREs at initial diagnosis of bone mets and were excluded from the analyses. Among the remaining 291 pts, mean (SD) age was 58.2 yrs (14.3 yrs), and 99% were women; 46% were Caucasian and 48% were African-American. Median duration of follow-up after diagnosis of bone mets was 16.1 months (mos). At 12 mos, cumulative incidence of SREs was 44.5% (SCC, 5.2%; PF, 21.0%; SCC and/or PF, 23.3%; SB, 7.6%; RT, 34.3%) (Table). Corresponding figures at 24 mos were 53.8% (SCC, 7.5%; PF, 29.3%; SCC and/or PF, 32.5%; SB, 9.4%; RT, 41.7%). Approximately one-half (45.0%) of study subjects received intravenous bisphosphonates prior to SRE. Conclusions: Pts with BC in routine clinical practice are at high risk of SREs following initial diagnosis of bone mets. [Table: see text]

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Risk of skeletal-related events (SREs) in patients with lung cancer (LC) and newly diagnosed metastases to bone.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e18107 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e18107-e18107

Author(s):

Kathryn E. Richert-Boe ◽

John Edelsberg ◽

Charu Taneja ◽

Lois Lamerato ◽

Andrew Glass ◽

...

Keyword(s):

Clinical Practice ◽

Cumulative Incidence ◽

Randomized Clinical Trials ◽

Pathologic Fracture ◽

Cord Compression ◽

Routine Clinical Practice ◽

Initial Diagnosis ◽

Newly Diagnosed ◽

Risk Of Death

e18107 Background: Bone is a common site of metastatic involvement in patients (pts) with LC. Bony metastases (mets) are often associated with SREs (spinal cord compression [SCC], pathologic fracture [PF], surgery to bone [SB], radiotherapy to bone [RT]). Skeletal complications cause significant morbidity and mortality. Current estimates of SRE risk come principally from randomized clinical trials. Information from routine clinical practice is limited. Methods: Using the tumor registry and electronic data stores at a large U.S. Midwest healthcare system that serves approximately 800,000 persons, we retrospectively identified all pts aged ≥18 yrs with primary LC and newly diagnosed bone mets between 1/1/95 and 12/31/09. Electronic medical records were reviewed by trained abstractors for evidence of SREs between date of bone mets diagnosis and death, loss to follow-up, or end of study. Cumulative incidence of SREs was estimated in the presence of competing risk of death. Results: We identified a total of 272 pts with primary LC and newly diagnosed bone mets; 66 pts had evidence of SREs at initial diagnosis of bone mets and were excluded from the analyses. Among the remaining 206 pts, mean (SD) age was 65.7 yrs (10.5 yrs) and 66% were male; 47% were Caucasian and 50% were African-American. Median duration of follow-up after diagnosis of bone mets was 3.0 months (mos). At 6 mos, cumulative incidence of SREs was 45.6% (SCC, 6.9%; PF, 20.6%; SCC and/or PF, 25.0%; SB, 4.1%; RT, 34.7%) (Table). Corresponding figures at 12 mos were 50.8% (SCC, 6.9%; PF, 24.1%; SCC and/or PF, 28.3%; SB, 4.1%; RT, 39.8%). Relatively few pts (17.5%) received intravenous bisphosphonates prior to SRE. Conclusions: Pts with LC in routine clinical practice are at high risk of SREs following initial diagnosis of bone mets. [Table: see text]

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Risk of skeletal-related events (SREs) in patients with breast cancer (BC) and newly diagnosed metastases to bone.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.27_suppl.91 ◽

2012 ◽

Vol 30 (27_suppl) ◽

pp. 91-91

Author(s):

Charu Taneja ◽

Lois Lamerato ◽

Andrew Glass ◽

Kathryn E. Richert-Boe ◽

John Edelsberg ◽

...

Keyword(s):

Clinical Practice ◽

Cumulative Incidence ◽

Randomized Clinical Trials ◽

Pathologic Fracture ◽

Cord Compression ◽

Routine Clinical Practice ◽

Initial Diagnosis ◽

Newly Diagnosed ◽

Risk Of Death

91 Background: Bone is a common site of metastatic involvement in patients (pts) with BC. Bony metastases (mets) are often associated with SREs (spinal cord compression [SCC], pathologic fracture [PF], surgery to bone [SB], radiotherapy to bone [RT]). Skeletal complications cause significant morbidity and mortality. Current estimates of SRE risk come principally from randomized clinical trials. Information from routine clinical practice is limited. Methods: Using the tumor registry and electronic data stores at a large U.S. Midwest healthcare system that serves approximately 800,000 persons, we retrospectively identified all pts aged ≥18 yrs with primary BC and newly diagnosed bone mets between 1/1/95 and 12/31/09. Electronic medical records were reviewed by trained abstractors for evidence of SREs between date of bone mets diagnosis and death, loss to follow-up, or end of study. Cumulative incidence of SREs was estimated in the presence of competing risk of death. Results: We identified a total of 378 pts with primary BC and newly diagnosed bone mets; 87 pts had evidence of SREs at initial diagnosis of bone mets and were excluded from the analyses. Among the remaining 291 pts, mean (SD) age was 58.2 yrs (14.3 yrs), and 99% were women; 48% were African-American and 46% were Caucasian. Median duration of follow-up after diagnosis of bone mets was 16.1 months (mos). At 12 mos, cumulative incidence of SREs was 44.5% (SCC, 5.2%; PF, 21.0%; SCC and/or PF, 23.3%; SB, 7.6%; RT, 34.3%) (Table). Corresponding figures at 24 mos were 53.8% (SCC, 7.5%; PF, 29.3%; SCC and/or PF, 32.5%; SB, 9.4%; RT, 41.7%). Approximately one-half (45.0%) of study subjects received intravenous bisphosphonates prior to SRE. Conclusions: Pts with BC in routine clinical practice are at high risk of SREs following initial diagnosis of bone mets. [Table: see text]

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Practical update for the use of bone-targeted agents in patients with bone metastases from metastatic breast cancer or castration-resistant prostate cancer

Current Oncology ◽

10.3747/co.27.6631 ◽

2020 ◽

Vol 27 (4) ◽

Author(s):

D. Southcott ◽

A. Awan ◽

K. Ghate ◽

M. Clemons ◽

R. Fernandes

Keyword(s):

Prostate Cancer ◽

Bone Metastases ◽

Metastatic Breast ◽

Pathologic Fracture ◽

Dose Schedule ◽

Cord Compression ◽

Targeted Agents ◽

Castration Resistant Prostate Cancer ◽

Skeletal Related Events ◽

Breast And Prostate Cancer

Bone metastases are a significant source of morbidity and mortality for patients with breast and prostate cancer. In this review, we discuss key practical themes regarding the use of bone-targeted agents (btas) such as bisphosphonates and denosumab for managing bony metastatic disease. The btas both delay the onset and reduce the incidence of skeletal-related events (sres), defined as any or all of a need for radiation therapy or surgery to bone, pathologic fracture, spinal cord compression, or hypercalcemia of malignancy. They have more modest benefits for pain and other quality-of-life measures. Regardless of the benefits of btas, it should always be remembered that the palliative management of metastatic bone disease is multimodal and multidisciplinary. The collaboration of all disciplines is essential for optimal patient care. Special consideration is given to these key questions: What are btas, and what is their efficacy? What are their common toxicities? When should they be initiated? How do we choose the appropriate bta? What is the appropriate dose, schedule, and duration of btas?

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Skeletal related events (SREs) in metastatic androgen independent prostate cancer (AIPC) treated with docetaxel-based chemotherapy: Results from ASCENT

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4614 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4614-4614 ◽

Cited By ~ 1

Author(s):

J. S. Chan ◽

C. W. Ryan ◽

P. M. Venner ◽

D. P. Petrylak ◽

G. S. Chatta ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Trial ◽

Cord Compression ◽

Entire Group ◽

Large Prospective Study ◽

Free Survival ◽

Skeletal Related Events ◽

The Impact ◽

Androgen Independent

4614 Background: Docetaxel prolongs survival in AIPC patients and zoledronic acid (ZA) reduces the incidence of SREs. The SRE incidence of patients treated with docetaxel-based chemotherapy has not previously been reported. Methods: ASCENT was a randomized clinical trial that compared weekly DN-101 (calcitriol, 45 μg p.o. on day 1) plus docetaxel (36 mg/m2 iv on day 2 for 3 weeks of a 4-week cycle) to placebo plus docetaxel in patients with chemotherapy-naïve metastatic AIPC. ZA use was not restricted. SRE-free survival was described for the entire group and then compared for patients randomly assigned to DN-101 or placebo and stratified by ZA use. Statistical comparisons were conducted using Cochran-Mantel-Haenszel for incidence and log-rank for SRE-free survival. Results: With a median follow-up of 18.3 months, 33% of subjects experienced at least one SRE and the overall median SRE-free survival was 13 (95% CI 10.5–14.3) months. The incidence of SRE by type was: radiation to bone (18.8%), fracture (10%), spinal cord compression (4%), surgery to bone (0.4%). Eighty-five (34%) patients received ZA. The study was not adequately powered to measure the impact of DN-101 or ZA on SRE endpoints. Exploratory analyses showed a trend for an increase in SRE-free survival (HR 0.78, p = 0.13) of DN-101-treated patients. SRE-free survival and incidence for subgroups were examined ( Table ). Conclusions: This is the first report of SRE incidence in a large, prospective study of docetaxel-based therapy. Improved therapies for reducing SREs in AIPC are needed because the risk of SREs remains high despite the use of modern chemotherapy and ZA. [Table: see text] [Table: see text]

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Five year follow up of a phase II study of cytotoxic immunotherapy combined with radiation in newly diagnosed prostate cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4635 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4635-4635 ◽

Cited By ~ 3

Author(s):

L. K. Aguilar ◽

B. Teh ◽

W. Mai ◽

J. Caillouet ◽

G. Ayala ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Controlled Trial ◽

Pathologic Complete Response ◽

Low Risk ◽

Control Group ◽

Newly Diagnosed ◽

Kinase Gene ◽

Cell Immunity

4635 Background: In the U.S. there are about 70,000 annual prostate cancer recurrences. The purpose of this study is to evaluate a product to decrease incidence of recurrence. This study is based on objective clinical responses in Phase I studies with AdV-tk (ProstAtak™, Advantagene, Inc) as monotherapy in recurrent disease and preclinical data demonstrating synergy between AdV-tk and radiation. AdV-tk is an adenoviral vector expressing the herpes thymidine kinase gene delivered to the prostate via TRUS-guided injection followed by 14 days of oral prodrug. The mechanisms of function involve direct tumor cytotoxicity, local elicitation of danger signals, recruitment and activation of antigen presenting cells and stimulation of systemic anti-tumor T-cell immunity. Method: AdV-tk was evaluated in combination with radiation in 66 newly diagnosed patients: 33 low risk (Arm A, PSA <10, Gleason <7, and T1c-T2a) and 33 intermediate-high risk (Arm B, PSA ≥10, Gleason ≥7, or T2b-T3). Arm A received two treatments with AdV-tk, immediately before and 14 days into radiation. Arm B received an additional treatment at initiation of androgen deprivation therapy. Results: Two surrogate and one definitive end-point were evaluated. Frequency of patients in Arm A with PSA nadir ≤0.2 ng/ml was 71% vs 56% in a control group of concurrent patients without AdV-tk. The two-year pathologic complete response (pCR) rate by sextant biopsy was 90% in Arm A and 94% in Arm B, compared to an expected range of 70–73%. Freedom from failure (FFF) after 60 month median follow up is 100% for Arm A and 90% for Arm B (95% for intermediate, 75% for high risk) vs best reported results of 79–90% for low risk and 48–79% for intermediate-high risk patients. The three failures in Arm B occurred within months after treatment leading to a Kaplan-Meier curve that plateaus at 90% beyond year 3. This is notably different than previous reports in which the curves continue to drop beyond year 5. Conclusion: These results suggest that AdV-tk combined with radiation therapy may significantly reduce the recurrence rate in patients with prostate cancer, particularly in patients with intermediate-high risk disease. A randomized controlled trial is warranted. [Table: see text]

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Disease-specific survival outcomes in lymph node–positive patients with prostate cancer treated with radiotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.182 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 182-182 ◽

Cited By ~ 1

Author(s):

G. Crehange ◽

V. K. Weinberg ◽

A. Izaguirre ◽

C. C. Hsu ◽

I. J. Hsu ◽

...

Keyword(s):

Prostate Cancer ◽

Disease Free Survival ◽

External Beam Radiation ◽

Survival Outcomes ◽

Primary Therapy ◽

Newly Diagnosed ◽

Beam Radiation ◽

Androgen Ablation ◽

Disease Free

182 Background: Involvement of regional lymph nodes (LN+) at the time of prostate cancer (PCa) diagnosis is widely regarded as an adverse prognostic factor associated with poor outcome. No commonly utilized treatment, composed of any combination of androgen ablation, surgery and radiation, has proven to be superior for survival. This study will evaluate the clinical survival outcomes of patients (pts) with newly diagnosed LN+ PCa at the University of California San Francisco (UCSF). Methods: All newly diagnosed LN+ PCa pts treated with External Beam Radiation Therapy (EBRT) as primary therapy or after surgery, each with and without androgen ablation between 1987 and 2009 were included. All pts had confirmed pathologic or radiologic LN+ whereas none had evidence of metastases on the work up. Cause Specific Survival (CSS), Disease Free survival (DFS) and biochemical control were measured from the start of treatment. PSA failure was determined by the Phoenix definition after EBRT and by a confirmed PSA >1 ng/mL following RP+EBRT. Results: A retrospective analysis identified 91 pts with LN+ at the time of diagnosis (75.8% high risk pts) with disease follow-up. Thirty-four (37%) were managed with exclusive EBRT alone (eRT), 18 pts (20%) with a combination of radical prostatectomy (RP) and adjuvant EBRT (RP+aRT) and 39 pts (43%) were treated with a combination of RP + salvage RT (RP+sRT). Overall 78% of patients also received hormone therapy (HT): 74.0% with eRT, 89% with RP+aRT and 79% with RP+sRT. The 10 years CSS estimates was 89% for eRT, 0% after RP+aRT and 88% after RP+sRT. The 10 years DFS estimates was 33% for eRT, 0% after RP+aRT and 75% after RP+sRT. Among pts remaining disease free the median follow-up is 38 mos for eRT, 26 mos for RP+aRT and 64 mos for RP+sRT. The last PSA for these patients was <0.1 for 85% of all patients which included 47% following eRT, 100% after RP+aRT and 97% after RP+sRT. There were 7 deaths due to PCa occurring between 5 and 73 mos from the start of EBRT. Conclusions: The results of the current analysis indicate that some pts with LN+ from PCa have prolonged disease free outcomes; and for these men, aggressive treatment may be appropriate. No significant financial relationships to disclose.

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