The Royal Marsden Hospital and The Institute of Cancer Research

London, United Kingdom

The Royal Marsden Hospital and The Institute of Cancer Research

London, United Kingdom

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PubMed | University of Michigan, Oncology, U.S. Biomarker Oncology, Medical Oncology and 10 more.
Type: | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2016

Abiraterone may suppress androgens that stimulate breast cancer growth. We conducted a biomarker analysis of circulating tumor cells (CTCs), formalin-fixed paraffin-embedded tissues (FFPETs), and serum samples from postmenopausal estrogen receptor (ER)+ breast cancer patients to identify subgroups with differential abiraterone sensitivity.Patients (randomized 1:1:1) were treated with 1,000 mg/d abiraterone acetate + 5 mg/d prednisone (AA), AA + 25 mg/d exemestane (AAE), or exemestane. The biomarker population included treated patients (n = 293). The CTC population included patients with {greater than or equal to} 3 baseline CTCs (n = 104). Biomarker (e.g., androgen receptor [AR], ER, Ki-67, CYP17) expression was evaluated. Cox regression stratified by prior therapies in the metastatic setting (0/1 vs. 2) and setting of letrozole/anastrozole (adjuvant vs. metastatic) was used to assess biomarker associations with progression-free survival (PFS).Serum testosterone and estrogen levels were lowered and progesterone increased with AA. Baseline AR or ER expression was not associated with PFS in CTCs or FFPETs for AAE versus exemestane but dual positivity of AR and ER expression was associated with improved PFS (HR 0.41 [95% confidence interval (CI), 0.16-1.07], P = 0.070). For AR expression in FFPETs obtained < 1 year prior to first dose (n = 67), a trend for improved PFS was noted for AAE versus exemestane (HR 0.56 [95% CI, 0.24-1.33], P = 0.19).An AA pharmacodynamic effect was shown by decreased serum androgen and estrogen levels and increased progesterone. AR and ER dual expression in CTCs and newly obtained FFPETs may predict AA sensitivity.


Dearden C.,The Royal Marsden Hospital and The Institute of Cancer Research
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2012

B- and T-cell subtypes of prolymphocytic leukemia (PLL) are rare, aggressive lymphoid malignancies with characteristic morphologic, immunophenotypic, cytogenetic, and molecular features. Prognosis for these patients remains poor, with short survival times and no curative therapy. The advent of mAbs has improved treatment options. In B-PLL, rituximab-based combination chemoimmunotherapy is effective in fitter patients. TP53 abnormalities are common and, as for chronic lymphocytic leukemia, these patients should generally be managed using an alemtuzumab-based therapy. Currently, the best treatment for T-PLL is IV alemtuzumab, which has resulted in very high response rates of more than 90% when given as frontline treatment and a significant improvement in survival. Consolidation of remissions with autologous or allogeneic stem cell transplantation further prolongs survival times, and the latter may offer potential cure. The role of allogeneic transplantation with nonmyeloablative conditioning needs to be explored further in both T- and B-PLL to broaden the patient eligibility for what may be a curative treatment.

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