Comparative Analyses of Chromosome Alterations in Soft-Tissue Metastases within and across Patients with Castration-Resistant Prostate Cancer

Purpose Cabozantinib (XL184), an oral inhibitor of multiple receptor tyrosine kinases such as MET and VEGFR2, was evaluated in a phase II nonrandomized expansion study in castration-resistant prostate cancer (CRPC). Patients and Methods Patients received open-label cabozantinib at daily starting doses of 100 mg or 40 mg until disease progression or unacceptable toxicity. The primary end point was bone scan response, defined as ≥ 30% reduction in bone scan lesion area. Other efficacy end points included overall survival, pain, analgesic use, and biomarkers. Results One hundred forty-four patients sequentially enrolled in either a 100-mg (n = 93) or 40-mg (n = 51) study cohort. Ninety-one patients (63%) had a bone scan response, often by week 6. Treatment resulted in clinically meaningful pain relief (57% of patients) and reduction or discontinuation of narcotic analgesics (55% of patients), as well as improvements in measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Improvements in each of these outcomes were observed in both cohorts: bone scan response in 73% and 45%, respectively; reductions in measurable soft tissue disease in 80% and 79%, respectively. Median overall survival was 10.8 months for the entire population. Most common grade 3 or 4 adverse events were fatigue (22%) and hypertension (14%). Fewer dose reductions because of toxicity were required in the 40-mg group. Conclusion The evidence suggests that cabozantinib has clinically meaningful activity in CRPC. Cabozantinib resulted in improvements in bone scans, pain, analgesic use, measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Taken together, these phase II observations warrant further development of cabozantinib in prostate cancer.

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Tumor-directed PET imaging of metastases in metastatic castration-resistant prostate cancer (mCRPC) using Zr-89 labeled antiprostate-specific membrane antigen (PSMA) antibody J591.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.164 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 164-164

Author(s):

Jarett L. Feldman ◽

Michael J. Morris ◽

Scott T. Tagawa ◽

David M. Nanus ◽

Stephen Barnett Solomon ◽

...

Keyword(s):

Prostate Cancer ◽

Soft Tissue ◽

Pet Imaging ◽

Response Assessment ◽

Imaging Modalities ◽

Bone Lesions ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

External Domain ◽

Clinical Trial Information

164 Background: There is no standard imaging (SI) modality that specifically and accurately images prostate cancer (PC) metastases, hampering prognostication and response assessment. J591 is a humanized antibody that targets the external domain of PSMA. We have previously reported on the feasibility, PK and biodistribution properties of 89Zr-J591 in 10 patients (pts) (Pandit-Taskar et al, Eur J Nuc Med Img 2014). We now report on the targeting/accuracy in 50 pts with mCRPC. Methods: Following standard CT/MRI, bone scan (BS), and FDG PET imaging, 5 mCi of 89Zr-J591 was administered IV. 89Zr-J591 was imaged 6-8 days after injection. Positive (pos) scan findings were confirmed, where possible, with biopsies (bxs) in the following preference: concordant 89Zr-J591 and FDG pos, 89Zr-J591 and FDG mismatch, and a mismatch between SI and any PET. Results: Imaging: A total of 703 lesions in 50 pts were identified using all imaging modalities. Bone:538 total bone lesions were detected. 491(91%) lesions were present on J591 of which 99 were only evident by J591. BS identified 339 (63%), CT 301 (56%), and FDG 207 (38%). Soft Tissue: 165 total soft tissue lesions were detected. 90 (55%) were seen on J591 of which 17 were only evident by J591. CT identified 124 (75%) and FDG 88 (53%). Pathology:46 bx’s were evaluable (21 bone, 25 soft tissue) in 34 pts. Of the unique J591 lesions biopsied (bx’d), 5/7 were pos for PC. Bone: We bx’d 19 J591 pos lesions and 2 J591 neg sites. Overall, path concordance with J591 was: 89% true pos, 100% true neg, 11% false pos, and 0% false neg. Soft tissue: We bx’d 16 J591 pos lesions and 9 J591 neg sites. Of these, we found 88% true pos, 11% true neg, 13% false pos, and 89% false neg. Conclusions: J591 PET identifies additional disease in bone not seen using other imaging modalities. These lesions are highly likely to correspond to disease by bx. However, the tracer performed less well in soft tissue, with a high false neg rate. Clinical trial information: NCT01543659.

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