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Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer
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| Zeitschriftentitel: | Clinical Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | Clinical Cancer Research, 25, 2019, 2, S. 652-662 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
|
| Schlagwörter: |
| author_facet |
Vaishampayan, Ulka N. Podgorski, Izabela Heilbrun, Lance K. Lawhorn-Crews, Jawana M. Dobson, Kimberlee C. Boerner, Julie Stark, Karri Smith, Daryn W. Heath, Elisabeth I. Fontana, Joseph A. Shields, Anthony F. Vaishampayan, Ulka N. Podgorski, Izabela Heilbrun, Lance K. Lawhorn-Crews, Jawana M. Dobson, Kimberlee C. Boerner, Julie Stark, Karri Smith, Daryn W. Heath, Elisabeth I. Fontana, Joseph A. Shields, Anthony F. |
|---|---|
| author |
Vaishampayan, Ulka N. Podgorski, Izabela Heilbrun, Lance K. Lawhorn-Crews, Jawana M. Dobson, Kimberlee C. Boerner, Julie Stark, Karri Smith, Daryn W. Heath, Elisabeth I. Fontana, Joseph A. Shields, Anthony F. |
| spellingShingle |
Vaishampayan, Ulka N. Podgorski, Izabela Heilbrun, Lance K. Lawhorn-Crews, Jawana M. Dobson, Kimberlee C. Boerner, Julie Stark, Karri Smith, Daryn W. Heath, Elisabeth I. Fontana, Joseph A. Shields, Anthony F. Clinical Cancer Research Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer Cancer Research Oncology |
| author_sort |
vaishampayan, ulka n. |
| spelling |
Vaishampayan, Ulka N. Podgorski, Izabela Heilbrun, Lance K. Lawhorn-Crews, Jawana M. Dobson, Kimberlee C. Boerner, Julie Stark, Karri Smith, Daryn W. Heath, Elisabeth I. Fontana, Joseph A. Shields, Anthony F. 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-18-1473 <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>Cabozantinib is a multitargeted tyrosine kinase inhibitor that demonstrated remarkable responses on bone scan in metastatic prostate cancer. Randomized trials failed to demonstrate statistically significant overall survival (OS). We studied the dynamics of biomarker changes with imaging and biopsies pretherapy and posttherapy to explore factors that are likely to be predictive of efficacy with cabozantinib.</jats:p> <jats:p>Experimental Design: Eligibility included patients with metastatic castrate-resistant prostate cancer with normal organ function and performance status 0–2. Cabozantinib 60 mg orally was administered daily. Pretherapy and 2 weeks post, 99mTc-labeled bone scans, positron emission tomography with 18F-sodium fluoride (NaF-PET) and 18F-(1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) thymine (FMAU PET) scans were conducted. Pretherapy and posttherapy tumor biopsies were conducted, and serum and urine bone markers were measured.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>Twenty evaluable patients were treated. Eight patients had a PSA decline, of which 2 had a decline of ≥50%. Median progression-free survival (PFS) and OS were 4.1 and 11.2 months, respectively, and 3 patients were on therapy for 8, 10, and 13 months. The NaF-PET demonstrated a median decline in SUVmax of −56% (range, −85 to −5%, n = 11) and −41% (range, −60 to −25%, n = 9) for patients who were clinically stable and remained on therapy for ≥4 or &lt;4 cycles, respectively. The FMAU PET demonstrated a median decline in SUVmax of −44% (−60 to −14%) and −42% (−63% to −23%) for these groups. The changes in bone markers and mesenchymal epithelial transition/MET testing did not correlate with clinical benefit.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Early changes in imaging and tissue or serum/urine biomarkers did not demonstrate utility in predicting clinical benefit with cabozantinib therapy.</jats:p> </jats:sec> Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer Clinical Cancer Research |
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10.1158/1078-0432.ccr-18-1473 |
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American Association for Cancer Research (AACR), 2019 |
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American Association for Cancer Research (AACR), 2019 |
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1078-0432 1557-3265 |
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1078-0432 1557-3265 |
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American Association for Cancer Research (AACR) |
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Clinical Cancer Research |
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| title |
Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| title_unstemmed |
Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| title_full |
Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| title_fullStr |
Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| title_full_unstemmed |
Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| title_short |
Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| title_sort |
biomarkers and bone imaging dynamics associated with clinical outcomes of oral cabozantinib therapy in metastatic castrate-resistant prostate cancer |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/1078-0432.ccr-18-1473 |
| publishDate |
2019 |
| physical |
652-662 |
| description |
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Purpose:</jats:title>
<jats:p>Cabozantinib is a multitargeted tyrosine kinase inhibitor that demonstrated remarkable responses on bone scan in metastatic prostate cancer. Randomized trials failed to demonstrate statistically significant overall survival (OS). We studied the dynamics of biomarker changes with imaging and biopsies pretherapy and posttherapy to explore factors that are likely to be predictive of efficacy with cabozantinib.</jats:p>
<jats:p>Experimental Design: Eligibility included patients with metastatic castrate-resistant prostate cancer with normal organ function and performance status 0–2. Cabozantinib 60 mg orally was administered daily. Pretherapy and 2 weeks post, 99mTc-labeled bone scans, positron emission tomography with 18F-sodium fluoride (NaF-PET) and 18F-(1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) thymine (FMAU PET) scans were conducted. Pretherapy and posttherapy tumor biopsies were conducted, and serum and urine bone markers were measured.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results:</jats:title>
<jats:p>Twenty evaluable patients were treated. Eight patients had a PSA decline, of which 2 had a decline of ≥50%. Median progression-free survival (PFS) and OS were 4.1 and 11.2 months, respectively, and 3 patients were on therapy for 8, 10, and 13 months. The NaF-PET demonstrated a median decline in SUVmax of −56% (range, −85 to −5%, n = 11) and −41% (range, −60 to −25%, n = 9) for patients who were clinically stable and remained on therapy for ≥4 or &lt;4 cycles, respectively. The FMAU PET demonstrated a median decline in SUVmax of −44% (−60 to −14%) and −42% (−63% to −23%) for these groups. The changes in bone markers and mesenchymal epithelial transition/MET testing did not correlate with clinical benefit.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions:</jats:title>
<jats:p>Early changes in imaging and tissue or serum/urine biomarkers did not demonstrate utility in predicting clinical benefit with cabozantinib therapy.</jats:p>
</jats:sec> |
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| author | Vaishampayan, Ulka N., Podgorski, Izabela, Heilbrun, Lance K., Lawhorn-Crews, Jawana M., Dobson, Kimberlee C., Boerner, Julie, Stark, Karri, Smith, Daryn W., Heath, Elisabeth I., Fontana, Joseph A., Shields, Anthony F. |
| author_facet | Vaishampayan, Ulka N., Podgorski, Izabela, Heilbrun, Lance K., Lawhorn-Crews, Jawana M., Dobson, Kimberlee C., Boerner, Julie, Stark, Karri, Smith, Daryn W., Heath, Elisabeth I., Fontana, Joseph A., Shields, Anthony F., Vaishampayan, Ulka N., Podgorski, Izabela, Heilbrun, Lance K., Lawhorn-Crews, Jawana M., Dobson, Kimberlee C., Boerner, Julie, Stark, Karri, Smith, Daryn W., Heath, Elisabeth I., Fontana, Joseph A., Shields, Anthony F. |
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| description | <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>Cabozantinib is a multitargeted tyrosine kinase inhibitor that demonstrated remarkable responses on bone scan in metastatic prostate cancer. Randomized trials failed to demonstrate statistically significant overall survival (OS). We studied the dynamics of biomarker changes with imaging and biopsies pretherapy and posttherapy to explore factors that are likely to be predictive of efficacy with cabozantinib.</jats:p> <jats:p>Experimental Design: Eligibility included patients with metastatic castrate-resistant prostate cancer with normal organ function and performance status 0–2. Cabozantinib 60 mg orally was administered daily. Pretherapy and 2 weeks post, 99mTc-labeled bone scans, positron emission tomography with 18F-sodium fluoride (NaF-PET) and 18F-(1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) thymine (FMAU PET) scans were conducted. Pretherapy and posttherapy tumor biopsies were conducted, and serum and urine bone markers were measured.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>Twenty evaluable patients were treated. Eight patients had a PSA decline, of which 2 had a decline of ≥50%. Median progression-free survival (PFS) and OS were 4.1 and 11.2 months, respectively, and 3 patients were on therapy for 8, 10, and 13 months. The NaF-PET demonstrated a median decline in SUVmax of −56% (range, −85 to −5%, n = 11) and −41% (range, −60 to −25%, n = 9) for patients who were clinically stable and remained on therapy for ≥4 or &lt;4 cycles, respectively. The FMAU PET demonstrated a median decline in SUVmax of −44% (−60 to −14%) and −42% (−63% to −23%) for these groups. The changes in bone markers and mesenchymal epithelial transition/MET testing did not correlate with clinical benefit.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Early changes in imaging and tissue or serum/urine biomarkers did not demonstrate utility in predicting clinical benefit with cabozantinib therapy.</jats:p> </jats:sec> |
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| spelling | Vaishampayan, Ulka N. Podgorski, Izabela Heilbrun, Lance K. Lawhorn-Crews, Jawana M. Dobson, Kimberlee C. Boerner, Julie Stark, Karri Smith, Daryn W. Heath, Elisabeth I. Fontana, Joseph A. Shields, Anthony F. 1078-0432 1557-3265 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/1078-0432.ccr-18-1473 <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>Cabozantinib is a multitargeted tyrosine kinase inhibitor that demonstrated remarkable responses on bone scan in metastatic prostate cancer. Randomized trials failed to demonstrate statistically significant overall survival (OS). We studied the dynamics of biomarker changes with imaging and biopsies pretherapy and posttherapy to explore factors that are likely to be predictive of efficacy with cabozantinib.</jats:p> <jats:p>Experimental Design: Eligibility included patients with metastatic castrate-resistant prostate cancer with normal organ function and performance status 0–2. Cabozantinib 60 mg orally was administered daily. Pretherapy and 2 weeks post, 99mTc-labeled bone scans, positron emission tomography with 18F-sodium fluoride (NaF-PET) and 18F-(1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl) thymine (FMAU PET) scans were conducted. Pretherapy and posttherapy tumor biopsies were conducted, and serum and urine bone markers were measured.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>Twenty evaluable patients were treated. Eight patients had a PSA decline, of which 2 had a decline of ≥50%. Median progression-free survival (PFS) and OS were 4.1 and 11.2 months, respectively, and 3 patients were on therapy for 8, 10, and 13 months. The NaF-PET demonstrated a median decline in SUVmax of −56% (range, −85 to −5%, n = 11) and −41% (range, −60 to −25%, n = 9) for patients who were clinically stable and remained on therapy for ≥4 or &lt;4 cycles, respectively. The FMAU PET demonstrated a median decline in SUVmax of −44% (−60 to −14%) and −42% (−63% to −23%) for these groups. The changes in bone markers and mesenchymal epithelial transition/MET testing did not correlate with clinical benefit.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Early changes in imaging and tissue or serum/urine biomarkers did not demonstrate utility in predicting clinical benefit with cabozantinib therapy.</jats:p> </jats:sec> Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer Clinical Cancer Research |
| spellingShingle | Vaishampayan, Ulka N., Podgorski, Izabela, Heilbrun, Lance K., Lawhorn-Crews, Jawana M., Dobson, Kimberlee C., Boerner, Julie, Stark, Karri, Smith, Daryn W., Heath, Elisabeth I., Fontana, Joseph A., Shields, Anthony F., Clinical Cancer Research, Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer, Cancer Research, Oncology |
| title | Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| title_full | Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| title_fullStr | Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| title_full_unstemmed | Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| title_short | Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| title_sort | biomarkers and bone imaging dynamics associated with clinical outcomes of oral cabozantinib therapy in metastatic castrate-resistant prostate cancer |
| title_unstemmed | Biomarkers and Bone Imaging Dynamics Associated with Clinical Outcomes of Oral Cabozantinib Therapy in Metastatic Castrate-Resistant Prostate Cancer |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/1078-0432.ccr-18-1473 |