Defining the critical hurdles in cancer immunotherapy

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer

Explaining racial disparities in surgical survival: a tapered match analysis of patient and hospital factors

Objectives Evaluate whether hospital factors, including nurse resources, explain racial differences in Medicare black and white patient surgical outcomes and whether disparities changed over time.Design Retrospective tapered-match.Setting 571 hospitals at two time points (Early Era 2003–2005; Recent Era 2013–2015).Participants 6752 black patients and three sets of 6752 white controls selected from 107 001 potential controls (Early Era). 4964 black patients and three sets of 4964 white controls selected from 74 108 potential controls (Recent Era).Interventions Black patients were matched to white controls on demographics (age, sex, state and year of procedure), procedure (demographics variables plus 136 International Classification of Diseases (ICD)-9 principal procedure codes) and presentation (demographics and procedure variables plus 34 comorbidities, a mortality risk score, a propensity score for being black, emergency admission, transfer status, predicted procedure time).Outcomes 30-day and 1-year mortality.Results Before matching, black patients had more comorbidities, higher risk of mortality despite being younger and underwent procedures at different percentages than white patients. Whites in the demographics match had lower mortality at 30 days (5.6% vs 6.7% Early Era; 5.4% vs 5.7% Recent Era) and 1-year (15.5% vs 21.5% Early Era; 12.3% vs 15.9% Recent Era). Black–white 1-year mortality differences were equivalent after matching patients with respect to presentation, procedure and demographic factors. Black–white 30-day mortality differences were equivalent after matching on procedure and demographic factors. Racial disparities in outcomes remained unchanged between the two time periods spanning 10 years. All patients in hospitals with better nurse resources had lower odds of 30-day (OR 0.60, 95% CI 0.46 to 0.78, p<0.010) and 1-year mortality (OR 0.77, 95% CI 0.65 to 0.92, p<0.010) even after accounting for other hospital factors.Conclusions Survival disparities among black and white patients are largely explained by differences in demographic, procedure and presentation factors. Better nurse resources (eg, staffing, work environment) were associated with lower mortality for all patients

NPS Naval Research Program USV ASW Employment, June 1 – 30, 2014

Naval Research ProgramNPS Naval Research Program; Sponsor POC: CDR Eric Lednicky; NPS POC: CAPT Jeff HyinkJON: W4V0

Phase 1/2 study of orteronel (TAK-700), an investigational 17,20-lyase inhibitor, with docetaxel-prednisone in metastatic castration-resistant prostate cancer

© 2015 Springer Science+Business Media New York. Background: Docetaxel-prednisone (DP) is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC). Orteronel (TAK-700) is an investigational, selective, non-steroidal inhibitor of 17,20-lyase, a key enzyme in androgenic hormone production. This phase 1/2 study evaluated orteronel plus DP in mCRPC patients. Methods: Adult men with chemotherapy-naïve mCRPC, serum prostate-specific antigen (PSA) ≤5 ng/mL, and serum testosterone \u3c50 ng/dL received oral orteronel 200 or 400 mg twice-daily (BID) in phase 1 to determine the recommended dose for phase 2, plus intravenous docetaxel 75 mg/m2 every 3 weeks, and oral prednisone 5 mg BID. Phase 2 objectives included safety, pharmacokinetics, and efficacy. Results: In phase 1 (n∈=∈6, orteronel 200 mg; n∈=∈8, orteronel 400 mg), there was one dose-limiting toxicity of grade 3 febrile neutropenia at 400 mg BID. This dose was evaluated further in phase 2 (n∈=∈23). After 4 cycles, 68, 59, and 23 % of patients achieved ≤30, ≤50, and ≤90 % PSA reductions, respectively; median best PSA response was -77 %. Seven of 10 (70 %) RECIST-evaluable patients achieved objective partial responses. Median time to PSA progression and radiographic disease progression was 6.7 and 12.9 months, respectively. Dehydroepiandrosterone-sulfate (DHEA-S) and testosterone levels were rapidly and durably reduced. Common adverse events were fatigue (78 %), alopecia (61 %), diarrhea (48 %), nausea (43 %), dysgeusia (39 %), and neutropenia (39 %). Orteronel and docetaxel pharmacokinetics were similar alone and in combination. Conclusions: Orteronel plus DP was tolerable, with substantial reductions in PSA, DHEA-S, and testosterone levels, and evidence for measurable disease responses