SUMMARY: BOSULIF® (Bosutinib), an Abl and Src kinase inhibitor was approved by the FDA for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy. This trial included CML patients treated with imatinib followed by a second generation TKI. Five hundred and forty six (546) patients were enrolled in a single-arm, open-label, multi-center trial and these patients had either chronic phase (CP), accelerated phase (AP) or blast phase (BP) CML and were previously treated with at least one prior tyrosine kinase inhibitor (TKI). The primary endpoints for patients with CP CML were the rate of major cytogenetic response (MCyR) at week 24 and the duration of MCyR. The primary endpoints for patients with AP or BP CML were the rate of confirmed complete hematologic response (CHR) and overall hematologic response (OHR) by week 48. The MCyR at week 24 was 34% for those CP CML patients who received prior therapy with one TKI and 27% for those who received prior therapy with more than one TKI. The duration of MCyR among 53% of the patients who achieved MCyR at any time during the trial was 18 months, for patients with CP CML who had been treated with one prior TKI. For those CP CML patients treated with more than one TKI, the duration of MCyR among 51% of the patients who achieved MCyR at any time during the trial was 9 months. The CHR and OHR for AP CML who received at least one prior TKI were 30% and 55% respectively at week 48 whereas the BP CML group had a CHR and OHR of 15% and 28% respectively at week 48. BOSULIF® will be a welcome addition for those CML patients who had progressed on one or more tyrosine kinase inhibitors. Brummendorf TH, Cortes JE, Kantarjian H, et al. J Clin Oncol 29: 2011 (suppl; abstr 6535)
Month: September 2012
XTANDI® (Enzalutamide) now approved for Late-Stage Prostate Cancer
SUMMARY:The US Food and Drug Administration (FDA) approved XTANDI® (Enzalutamide), an oral agent, formerly known as MDV3100, for men with metastatic castration-resistant prostate cancer who had progressed on TAXOTERE® (Docetaxel) based chemotherapy regimen. The approval was based on the results from the AFFIRM clinical trial. XTANDI® is an androgen receptor antagonist with a significantly higher binding affinity for the androgen receptor (AR) compared to the antiandrogen bicalutamide and there by competitively inhibits the binding of androgens to the androgen receptor. Majority of the patients with advanced prostate cancer become refractory to hormone therapy because of increased production of androgen receptors by the tumors as well as mutated androgen receptors. The superiority of this novel agent, XTANDI®, is based on the fact that the expression of androgen receptor dependent genes are downregulated with XTANDI® leading to cell death or apoptosis, whereas with bicalutamide the expression of these genes are upregulated. Further XTANDI® continues to antagonize mutated androgen receptors on the prostate tumor cells in contrast to bicalutamide which behaves as an agonist. It is thus an androgen receptor signaling inhibitor (ARSI). The AFFIRM clinical trial is a randomized, multinational phase III study in which patients who had received prior docetaxel-based chemotherapy regimens were randomized 2:1 to receive either XTANDI®, 160 mg/day or placebo. Patients treated with XTANDI® had a median survival of 18.4 months, compared with 13.6 months for men treated with placebo, with a median OS advantage of 4.8 months and a reduction in the risk of death by 37%. Scher HI, Fizazi K, Saad F, et al. J Clin Oncol 30, 2012 (suppl 5; abstr LBA1)