Independent central review of clinical imaging remains the standard for oncology clinical trials with registration potential. A limited independent central review strategy has been proposed for solid tumor trials based on concordance between central and local evaluation of response. Concordance between independent central review and local evaluation of response in hematological malignancies is not known.
We retrospectively evaluated concordance between prospectively performed central and local assessments of response using the Revised Response Criteria for Malignant Lymphoma across two international, open-label, single-arm, registration studies of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma (N = 102) or systemic anaplastic large-cell lymphoma (N = 58).
Overall objective response rates were similar between assessors for both the trial in Hodgkin lymphoma (75% independent central review, 72% local evaluation) and the trial in anaplastic large-cell lymphoma (86% independent central review, 83% local evaluation). Patient-specific objective response concordance was also substantial (Hodgkin lymphoma: kappa = 0.68; anaplastic large-cell lymphoma: kappa = 0.74). Median progression-free survival was similar between assessors for patients with anaplastic large-cell lymphoma (14.3 months by independent central review (95% confidence interval: 6.9, -); 14.5 months by local evaluation (95% confidence interval: 9.4, -)), but longer by local evaluation in patients with Hodgkin lymphoma (5.8 months by independent central review (95% confidence interval: 5.0, 9.0); 9.0 months by local evaluation (95% confidence interval: 7.1, 12.0)). Median duration of response was longer by local evaluation in both malignancies, which was primarily attributable to earlier computed tomography and positron emission tomography-based scoring of progression by independent central review.
A limited independent review audit strategy for clinical trials of some lymphomas appears feasible and practical based on substantial concordance in assessments of overall objective response by central and local evaluation in two international, prospective, registration trials in lymphoma. Some variability between assessors in the time-to-event endpoints was observed, which appeared attributable to earlier assignments of progression by independent central review compared with local evaluation.
© The Author(s) 2016.

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Sunitinib is a multi-targeted tyrosine kinase inhibitor used in the treatment of advanced renal cell carcinoma (RCC) and imatinib-resistant/intolerant gastrointestinal stromal tumors (GIST).
A meta-analysis of 10 prospective clinical studies in advanced RCC and GIST was performed to support the development of pharmacokinetic (PK) and PK/pharmacodynamic (PD) models that account for the effects of important covariates. These models were used to make predictions with respect to the PK, safety, and efficacy of sunitinib when administered on the traditional 4-weeks-on/2-weeks-off schedule (Schedule 4/2) versus an alternative schedule of 2 weeks on/1 week off (Schedule 2/1).
The covariates found to have a significant effect on one or more of the PK or PD parameter studies included, age, sex, body weight, race, baseline Eastern Cooperative Oncology Group performance status, tumor type, and dosing schedule. The models predicted that, in both RCC and GIST patients, Schedule 2/1 would have comparable efficacy to Schedule 4/2, despite some differences in PK profiles. The models also predicted that, in both indications, sunitinib-related thrombocytopenia would be less severe when sunitinib was administered on Schedule 2/1 dosing compared with Schedule 4/2.
These findings support the use of sunitinib on Schedule 2/1 as a potential alternative to Schedule 4/2 because it allows for the management of toxicity without loss of efficacy.

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Busulfan (Bu)-containing regimens are commonly used in myeloablative regimens prior to allogeneic hematopoietic cell transplantation (HCT). Yet, there is considerable variability on how Bu is administered related to frequency (four times a day, Q6 or daily, Q24) and the combination with other chemotherapeutic agents (cyclophosphamide, Cy or fludarabine, Flu). A prospective cohort study of recipients of Bu-based conditioning according to contemporary practices was used to compare different approaches in using Bu (BuCy Q6 N=495; BuFlu Q24 N=331; BuCy Q24 N=96; BuFlu Q6 N=91) in patients with myeloid malignancies from 2009 to 2011. BuFlu Q24 recipients were more likely to be older and tended to have worse performance status and higher comorbid burden. The cumulative incidence of hepatic veno-occlusive disease (p=0.4), idiopathic pneumonia (p=0.5) and seizures (p=0.5) did not differ across groups. One-year HCT related mortality ranged from 12% to 16% (P=0.8), three-year relapse incidences ranged from 32% to 36% (p=0.8) and three-year overall survival ranged from 51% to 58% (p=0.2) across groups. This study demonstrates that the use of intravenous Bu Q6 or Q24 or accompanied by Cy or Flu have similar outcomes in the myeloablative setting for treatment of myeloid malignancies.
Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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Breast cancer is a frequent and treatable disease. However, when recurrent, breast cancer often becomes refractory to therapy and progresses into metastatic forms that are typically incurable. Thus, understanding and targeting the critical pathways underlying breast cancer recurrence is urgently needed to eradicate primary disease and achieve better prognosis. Recently, we have demonstrated that the ribosomal protein p70S6K is activated in residual breast cancer cells as a result of post-surgical inflammation and that interfering with its activity in the peri-operative setting strongly suppresses recurrence in a mouse model. In order to develop clinically-exploitable treatments targeting p70S6K, we have tested a newly generated compound, called FS-115. FS-115 potently inhibited p70S6K1 (IC50 35nM) with high selectivity over other AGC kinases or PI3K pathway kinases. In vitro, treatment with FS-115 efficiently blocked p70S6K activity in breast cancer cell lines and impaired colony formation and anchorage independent growth. Pharmacokinetic profiling showed that FS-115 exhibited high oral bioavailability, optimal plasma distribution and high brain penetrance. In nude mice, FS-115 strongly suppressed tumor take-rate and primary tumor growth. Oral dosing with FS-115 in a peri-operative schedule was effective in decreasing local recurrence of breast cancer and a long-term treatment schedule was well tolerated and efficiently suppressed distant metastasis formation. Altogether, we propose that FS-115 might be a good candidate for the treatment of breast cancer patients at high risk to relapse.
Our results confirm that inhibition of p70S6K represents a valuable opportunity for restraining loco-regional relapse and metastasis in breast cancer and identify in FS-115 a promising candidate-inhibitor to move from preclinical to clinical treatments.

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On May 6, 2016 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported presentations of clinical data for apaziquone to be presented at an oral presentation and a moderated poster session at the American Urological Association Education and Research Inc., being held in San Diego, California, from May 6-10, 2016 (Press release, Spectrum Pharmaceuticals, MAY 6, 2016, View Source [SID:1234512013]).

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For more information about the AUA Meeting and for a complete list of abstracts, please refer to the conference web site at View Source

Friday, May 6, 2016 1:00 PM-3:00 PM PT (Moderated Poster Session)

Abstract # Type Title First Author Location

MP13-07
Poster
Improved Efficacy of Adjuvant, Single Dose Intravesical Apaziquone by Timing post-Resection in Two Double
blind, Randomized, Placebo-Controlled Phase 3 Studies in Non-Muscle Invasive Bladder Cancer
Fred Witjes
Room 28 ABC

Saturday, May 7, 2016, 8:00 AM-10:00 AM PT (Podium Presentation)

Abstract # Type Title First Author Location

PD11-07
Podium
Integrated Results of Two Multicenter, Randomized, Placebo Controlled, Double Blind, Phase 3 Trials (SPI-611/612) of Single-Dose Intravesical Apaziquone Immediately Following Resection in Patients with Non-Muscle Invasive Bladder Cancer