Clin Cancer Res
-
Venetoclax is the first BCL2 inhibitor to enter routine clinical practice. It is an orally bioavailable small molecule that binds BCL2 very specifically. Acting as a pharmacologic mimic of the proteins that initiate apoptosis (a so-called BH3 mimetic), venetoclax rapidly induces apoptosis in chronic lymphocytic leukemia (CLL) cells, which express high levels of BCL2 and rely on it to maintain their survival. ⋯ Its use was approved by the FDA in April 2016 for patients with previously treated del(17p) CLL on the basis of a single-arm phase II trial demonstrating a 79% response rate and an estimated 1-year progression-free survival of 72% with 400 mg/day continuous therapy. This review focuses on venetoclax, its mechanism of action, pharmacology, and clinical trial data and seeks to place it in the context of rapid advances in therapy for patients with relapsed CLL, especially those with del(17p) CLL. Clin Cancer Res; 23(16); 4527-33. ©2017 AACR.
-
Purpose: To identify MRI-based radiomics as prognostic factors in patients with advanced nasopharyngeal carcinoma (NPC). Experimental Design: One-hundred and eighteen patients (training cohort: n = 88; validation cohort: n = 30) with advanced NPC were enrolled. A total of 970 radiomics features were extracted from T2-weighted (T2-w) and contrast-enhanced T1-weighted (CET1-w) MRI. ⋯ Conclusions: Multiparametric MRI-based radiomics nomograms provided improved prognostic ability in advanced NPC. These results provide an illustrative example of precision medicine and may affect treatment strategies. Clin Cancer Res; 23(15); 4259-69. ©2017 AACR.
-
Randomized Controlled Trial
Long-Term Responders on Olaparib Maintenance in High-Grade Serous Ovarian Cancer: Clinical and Molecular Characterization.
Purpose: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. Experimental Design: A comparative molecular analysis of Study 19 (NCT00753545), a randomized phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted. ⋯ Conclusions: Findings show that LT response to olaparib may be multifactorial and related to homologous recombination repair deficiency, particularly BRCA1/2 defects. The type of BRCA1/2 mutation warrants further investigation. Clin Cancer Res; 23(15); 4086-94. ©2017 AACR.
-
Purpose: Rucaparib is a potent, oral, small-molecule PARP inhibitor. This phase I-II study was the first to evaluate single-agent oral rucaparib at multiple doses. Experimental Design: Part 1 (phase I) sought to determine the MTD, recommended phase II dose (RP2D), and pharmacokinetics of oral rucaparib administered in 21-day continuous cycles in patients with advanced solid tumors. ⋯ Among 98 patients, 5 (5.1%) discontinued because of an adverse event (excluding disease progression). Conclusions: Rucaparib was tolerable and had activity in patients with platinum-sensitive germline BRCA1/2-mutated HGOC. Clin Cancer Res; 23(15); 4095-106. ©2017 AACR.
-
Purpose: We aimed to establish the MTD of the poly (ADP-ribose) (PAR) polymerase inhibitor, veliparib, in combination with carboplatin in germline BRCA1- and BRCA2- (BRCA)-associated metastatic breast cancer (MBC), to assess the efficacy of single-agent veliparib, and of the combination treatment after progression, and to correlate PAR levels with clinical outcome. Experimental Design: Phase I patients received carboplatin (AUC of 5-6, every 21 days), with escalating doses (50-20 mg) of oral twice-daily (BID) veliparib. In a companion phase II trial, patients received single-agent veliparib (400 mg BID), and upon progression, received the combination at MTD. ⋯ Lasting CRs were observed when the combination was administered first in the phase I trial. Further investigation of PAR level association with clinical outcomes is warranted. Clin Cancer Res; 23(15); 4066-76. ©2017 AACR.