Datchen Fritz Tai

Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer

OBJECTIVE The safety and efficacy of gemcitabine plus carboplatin (GC) or paclitaxel plus carboplatin (TC) induction regimens with or without paclitaxel consolidation therapy were assessed in ovarian cancer (OC). METHODS Patients with stage IC-IV OC were randomized to either GC (gemcitabine 1,000 mg/m(2), days 1 and 8, plus carboplatin area under the curve [AUC] 5, day 1) or TC (paclitaxel 175 mg/m(2) plus carboplatin AUC 6, day 1) every 21 days for up to six cycles. Patients with complete response (CR) were allowed optional consolidation with paclitaxel 135 mg/m(2) every 28 days for ≤ 12 months. Patients without CR received single-agent crossover therapy at induction doses/schedules until CR, disease progression (PD), or unacceptable toxicity. PD or death in 636 patients was required to compare induction arms with 80% statistical power for progression-free survival (PFS), the primary endpoint. RESULTS Randomized induction therapy was received by 820 of 919 patients enrolled; 352 patients with CR received paclitaxel consolidation whereas 155 patients without CR received single-agent crossover therapy. PFS was similar for GC and TC (median, 20.0 and 22.2 months, respectively; P=.199). Despite high censoring rates (>52%), overall survival was longer for TC (median, 57.3 versus 43.8 months for GC; P=.013). Controlling for patient characteristics including performance status, residual tumor size, and tumor stage, there was no statistical difference in a multivariate analysis (HR=1.22; 95% CI=0.99-1.52; P=.067). CONCLUSIONS GC does not improve PFS over TC as first-line induction chemotherapy in OC. Although favoring TC, overall survival analyses were limited by the study design and high censoring rates.

Phase 2 study of tabalumab, a human anti‐B‐cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma

In this double‐blind, Phase 2 study, 220 patients with relapsed/refractory multiple myeloma were randomly assigned 1:1:1 to receive placebo (N = 72), tabalumab 100 mg (N = 74), or tabalumab 300 mg (N = 74), each in combination with dexamethasone 20 mg and subcutaneous bortezomib 1·3 mg/m2 on a 21‐day cycle. No significant intergroup differences were observed among primary (median progression‐free survival [mPFS]) or secondary efficacy outcomes. The mPFS was 6·6, 7·5 and 7·6 months for the tabalumab 100, 300 mg and placebo groups, respectively (tabalumab 100 mg vs. placebo Hazard ratio (HR) [95% confidence interval (CI)] = 1·13 [0·80–1·59], P = 0·480; tabalumab 300 mg vs. placebo HR [95% CI] = 1·03 [0·72–1·45], P = 0·884). The most commonly‐reported treatment‐emergent adverse events were thrombocytopenia (37%), fatigue (37%), diarrhoea (35%) and constipation (32%). Across treatments, patients with low baseline BAFF (also termed TNFSF13B) expression (n = 162) had significantly longer mPFS than those with high BAFF expression (n = 55), using the 75th percentile cut‐off point (mPFS [95% CI] = 8·3 [7·0–9·3] months vs. 5·8 [3·7–6·6] months; HR [95% CI] = 1·59 [1·11–2·29], P = 0·015). Although generally well tolerated, PFS was not improved during treatment with tabalumab compared to placebo. A higher dose of 300 mg tabalumab did not improve efficacy compared to the 100 mg dose. Nonetheless, BAFF appears to have some prognostic value in patients with multiple myeloma.

Phase 2 randomized study of enzastaurin (LY317615) for lung cancer prevention in former smokers

Chemoprevention for lung cancer with nutraceutical or anti‐inflammatory agents has had mixed clinical benefit. Novel targeted agents hold the promise of greater efficacy and selectivity. The authors of this report evaluated enzastaurin, a selective protein kinase C‐β (PKC‐β) inhibitor with antiproliferative and proapoptotic properties, in former smokers.

Phase II Study of Gemcitabine and Bevacizumab As First-Line Treatment in Taxane-Pretreated, HER2-Negative, Locally Recurrent or Metastatic Breast Cancer

BACKGROUND In first-line treatment of metastatic breast cancer, the best use of the available therapeutic agents is unclear. This study evaluated the efficacy and safety of combined therapy with bevacizumab and gemcitabine. PATIENTS Women who were to undergo first-line treatment for locoregionally recurrent or metastatic breast cancer were eligible. Patients must have received a taxane-containing regimen in the neoadjuvant and/or adjuvant setting with a ≥ 12-month disease-free interval. METHODS This was a single-arm, phase II trial. On day 1 of each 14-day cycle, patients received gemcitabine (2500 mg/m(2)) followed by bevacizumab (10 mg/kg). Patients were treated until complete response, progressive disease (PD), or intolerable toxicity. The primary endpoint was progression-free survival (PFS). RESULTS Fifty-two women were enrolled and treated. The median PFS was 4.8 months (95% confidence interval [CI], 3.4-7.6), the 1-year overall survival rate was 68.7% (95% CI, 54.1%-79.5%), and the response rate was 21.4% (95% CI, 10.3%-36.8%). The clinical benefit rate was 35.7%. The median PFS in the triple-negative (n = 19) and non-triple-negative (n = 33) subsets was 3.9 months (95% CI, 2.7-11.7) and 4.9 months (95% CI, 3.4-8.1), respectively. The most common (all grades) drug-related adverse events (AEs) were nausea (51.9%), fatigue (46.2%), decreased appetite (25.0%), and anemia (25.0%). The most common grade 3 or grade 4 drug-related AEs were neutropenia (13.5%), leukopenia (11.5%), and hypertension (7.7%). CONCLUSION Although the gemcitabine-bevacizumab doublet appears active, the median PFS was lower than expected. There were no unexpected safety signals at this dose and schedule of this combination.

Fixed-dose rate gemcitabine plus carboplatin in relapsed, platinum-sensitive ovarian cancer patients: Results of a three-arm Phase I study

OBJECTIVES Standard infusion of gemcitabine plus carboplatin showed improved efficacy compared to carboplatin alone in patients with platinum-sensitive (Pt-S) ovarian cancer (OC). Fixed-dose rate (FDR) administration of gemcitabine produces more efficient intracellular phosphorylation of gemcitabine to its active form. This study was designed to identify the maximum tolerated dose (MTD), toxicity profile, and response rate of FDR gemcitabine plus carboplatin in Pt-S OC. METHODS Patients with measurable OC relapsing > or =6 months after exposure to platinum (N=60) were assigned to one of three treatment cohorts, each with a different delivery schedule and escalating doses of both FDR gemcitabine (10 mg/m(2)/min) and standard infusion carboplatin (60 min). MTDs were determined using dose-limiting toxicities (DLTs). Measurable disease was assessed using modified RECIST criteria. CA-125 levels were evaluated using Rustin criteria. Toxicities were assessed using NCI Common Toxicity Criteria, version 2.0. RESULTS The MTD of Arm 1 was FDR gemcitabine 1000 mg/m(2) on days 1 and 8 plus carboplatin AUC 5 on day 1, every 21 days. The MTD of Arm 2 was FDR gemcitabine 1000 mg/m(2) on days 1 and 8 plus carboplatin AUC 2.5+AUC 2.5 on days 1 and 8, every 21 days. Patient accrual on Arm 3 consisting of bi-weekly FDR gemcitabine plus carboplatin was terminated because dose level 1 exceeded the MTD. Overall response rates were 38.1% (Arm 1), 58.8% (Arm 2), and 44.4% (Arm 3). CONCLUSIONS FDR gemcitabine+carboplatin on a 21-day schedule was active and produced no unusual safety signals in patients with Pt-S OC.

The Patient Experience with Soft Tissue Sarcoma: A Systematic Review of the Literature

BackgroundSoft tissue sarcomas (STS) are a heterogenous group of rare tumors that involve the connective tissue in the body (e.g. muscle, tendons). As with many rare tumors, little is known about the impact of STS on patient well-being.ObjectiveThe aim of this review was to better understand current knowledge related to patient experience and quality of life (QOL) following diagnosis of STS.MethodsA systematic review of English-language articles published from 2005 to 2015 was conducted in the PubMed/MEDLINE, Embase, PsychINFO, and Evidence-Based Medicine databases. The review included recent conference proceedings and advocacy websites. Articles were eligible if they included adult STS patient-reported outcomes (PROs) or details on patient experience.ResultsOverall, 3430 articles were identified and 20 were eligible for inclusion. Of these, 14 were clinical studies that included PRO measures, 1 summarized PRO measures used in STS studies, and 5 described the STS patient experience. Patients with STS report a range of impacts on QOL, including emotional well-being, body image, functional deficit following surgery, and practical considerations such as child care and work.ConclusionsFew studies have published either qualitative or quantitative data on the patient experience with STS. While STS has a measurable impact on QOL, there is a lack of detailed information in the published literature. Although PROs are used in clinical studies of STS, they are not STS-specific and may not capture the unique needs of this population. There is a need for qualitative research to better understand both patient and caregiver experiences in STS.

Understanding the patient experience with soft tissue sarcoma: A systematic review of the literature.

61 Background: Soft tissue sarcomas (STS) are a heterogenous group of rare tumors that involve the connective tissue in the body. As with many rare tumors, little is known about the impact of STS on patient well-being. The objective of this review was to understand patient experience and quality of life (QOL) following diagnosis of STS. METHODS This was a systematic review of English language articles published between 2005-2015 in PubMed/Medline, Embase, PsychINFO, and Evidence-Based Medicine. The review included recent conference proceedings and resources from advocacy websites. Articles were considered relevant if they included adult STS patient reported outcomes (PROs) or details on patient experience. RESULTS Of the 3,430 articles identified, 20 were eligible for inclusion. Of these, 14 were clinical studies that included PRO measures, 1 summarized PRO measures used in STS studies, and 5 described the STS patient experience. Patients with STS report a variety of concerns including emotional well-being (e.g. anxiety, depression), body image, functional deficit following surgery, and practical considerations such as obtaining child care and ability to work. Reports of patient experience vary widely given the heterogeneity of STS and individualized treatment. In clinical studies that used PROs, the European Organization for Research and Treatment of Cancer QOL Questionnaire Core 30 (EORTC QLQ-C30) was the most commonly used cancer-specific measure (N = 5) followed by the Functional Assessment of Cancer Therapy-General (N = 2). The generic EQ-5D was used in 5 publications but was limited to the visual analog scale portion of the measure in two of these studies. Similar to other cancers, STS patients report lower QOL when compared to the general population. CONCLUSIONS Few studies have published either qualitative or quantitative data on the patient experience with STS. While STS has a measurable impact on QOL, there is a lack of detailed information in the published literature. Although PROs are often used in clinical studies of STS, they are not STS-specific tools and may not capture the unique needs of this population. There is a need for qualitative research to better understand the patient perspective of STS.

Phase II study of gemcitabine (G) and bevacizumab (B) as first-line treatment in taxane-pretreated, HER2-negative, locally recurrent or metastatic breast cancer (MBC).

1052 Background: Bevacizumab with chemotherapy has shown improvement in progression-free survival (PFS) in MBC patients (pts) (Miller 2007; Miles 2008; Brufsky 2009; Robert, et al 2009). We examined the efficacy/safety of combining B with G as first-line therapy in taxane-pretreated MBC pts. METHODS This US, multicenter, single arm, open-label trial enrolled 52 pts. Eligibility criteria included: HER2-negative, recurrent or MBC, performance status (PS) 0-1, and prior taxane as neoadjuvant and/or adjuvant therapy with a >12 month disease-free interval. Pts received G 2500 mg/m2 plus B 10 mg/kg on day (d) 1, both in 14-d cycles. Pts were treated until progressive disease (PD), complete response (CR), or intolerable toxicity. The primary endpoint was PFS; secondary endpoints were overall response rate (ORR), 1-year survival rate, and safety. Toxicities were graded according to NCI CTC v 3.0. RESULTS Between March 2008 and January 2010, 52 women were enrolled and treated. Median age 55 (range 28-78); 30 ER+/PR+; 19 ER-/PR-/HER2-; PS 0/1, 28/24 pts. Five pts experienced ≥1 serious drug-related adverse event (AE). Ten pts discontinued due to AEs; 5 pts were hospitalized for drug-related AEs. Drug-related treatment-emergent AEs (TEAEs) of all grades present in >20% of pts were: nausea (51.9%), fatigue (46.2%), anorexia (21.2%), neutropenia (23.1%), and anemia (21.2%). Grade (Gr) 3 drug-related TEAEs occurring in ≥2% of pts were neutropenia (13.5%), leukopenia (7.7%), hypertension (7.7%), thrombocytopenia (3.8%), and anemia (3.8%). Two pts experienced Gr 4 TEAEs: 1 pt, hemolytic uremic syndrome + acute renal failure + leukopenia; 1 pt, pulmonary embolism. There were no deaths from study drug toxicity. The median number of cycles received was 8 (range 1-30). Median dose intensities were: G, 96.8% and B, 97.6%. The ORR was 21.4% (0 CR; 9 partial responses). Nineteen (45.2%) pts had stable disease. Median PFS is 4.8 months (95% confidence interval: 3.4-7.2). The 1-year overall survival rate is 67.1%. CONCLUSIONS Therapy with G+B is well tolerated with demonstrated activity in this poor prognosis group. Final efficacy data will be presented at the meeting.

Phase II study of gemcitabine (G) and bevacizumab (B) as first-line treatment in taxane-pretreated, HER2-negative, locally recurrent or metastatic breast cancer (MBC): Interim safety analysis.

1148 Background: The combination of bevacizumab with taxane-, anthracycline-, or capecitabine-based chemotherapy has yielded significant improvement in progression-free survival (PFS) in pts with MBC (Miller 2007; Miles 2008; Robert 2009). We examined the efficacy and safety of combining B with G as first-line therapy in taxane pretreated MBC pts and report an interim safety analysis of the first 39 enrolled pts. Methods: This US, multicenter, nonrandomized, open-label trial will enroll 51 pts. Eligible pts have HER2-negative, recurrent or MBC, PS 0-1, and must have received a taxane as neoadjuvant and/or adjuvant therapy with a ≥12 month disease-free interval. Pts received G 2,500 mg/m2 on d 1 plus B 10 mg/kg on d 1, both in 14-day cycles and were treated until progressive disease (PD), complete response, or intolerable toxicity. The primary endpoint is PFS and the secondary endpoints are overall response rate, 1 year survival rate, and safety. Toxicities are graded according to NCI CTC v3.0. Results: Be...