4003 Background: SU 37.5 mg/day continuous daily dosing vs placebo (PBO) was assessed in pts with progressive, well-differentiated pancreatic endocrine tumors in a phase III trial (NCT00428597). SU demonstrated prolonged median progression-free survival (PFS) vs PBO (11.4 vs. 5.5 months; p = 0.0001) and was well tolerated. The trial included PRO assessments, reported here. Methods: Pts completed the validated, 15-domain, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) v 3.0, on Day 1, every 4 wks (cycle) thereafter, and at end of treatment/withdrawal. Between-treatment comparison of estimated mean differences in change from baseline was carried out using repeated measures mixed-effects models. Statistical (2-sided p value; 0.05 level) and clinical (≥ 10 point difference, minimally important difference; Osoba et al. J Clin Oncol 1998;16:139-44) significance of differences were assessed. Results: QLQ-C30 data were available for 73/86 and 71/85 pts in SU and PBO arms. PRO analysis was limited to the first 10 cycles, during which each arm had ≥ 10 pts. All 15 QLQ-C30 domain scores had a ≤ 7-point mean difference between arms at baseline. Analysis based on mixed-effects model found pts in the SU arm had overall clinically and statistically significant worsening of diarrhea (diff = 21.38, p < 0.001). In this arm there was also a significant trend towards worsening of insomnia (diff = 7.753, p = 0.0372) vs PBO. However, in QoL, cognitive, emotional, physical, role, and social functioning domains and other symptoms and scales, there were no overall clinically or statistically significant differences. There was no significant difference between arms in observed mean change from baseline in global QoL nor in most other domains, when compared using the 2-sample t-test. Additional analyses are planned. Conclusions: SU resulted in significant PFS improvement vs PBO and maintained global health-related QoL in pts with pancreatic NET. The expected toxicity of diarrhea had limited impact on global QoL and functioning scales in patients treated with SU. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Ansar, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, K V Pharmaceuticals, Lilly, Merck, Novartis, Pfizer, R W Johnson Pharmaceuticals, sanofi-aventis, Takeda, Tercica Pfizer Pfizer Abbott Laboratories, American Diabetes Association, Arcion Therapeutics, GlaxoSmithKline, Lilly, Merck Research Labs, Mitsubishi/Medpace, Inc, NIH/NIA, Old Dominion Research Foundation, Pfizer, Reliant Pharmaceuticals, sanofi-aventis Pfizer
e15061 Background: Targeted therapies are now the standard of care for mRCC with use and expected outcomes defined by clinical trials. What are "real world" patterns of use and survival outcomes in mRCC patients (pts) treated in community oncology (COMM) settings? Methods: We reviewed a retrospective registry of adult mRCC pts from 11 COMM oncology practices, diagnosed since 1/2007 and not enrolled in a trial. Demographics, disease characteristics, treatment patterns and outcomes were recorded from the EMR and supplemented with chart abstraction.Pts were grouped by treatment sequence reflecting up to 3 exposures based on drug mechanism of action (VEGFR TKI [TKI] or mTOR inhibitor [mTOR]). Other pts received a non-TKI, non-mTOR therapy in the 1st three exposures (e.g., bevacizumab, cytokines, combinations, etc.). No Therapy pts received no systemic therapy as of data analysis. Survival analyses included Kaplan-Meier methods and Cox regression. Results: 255 patient/disease characteristics included: age 65±11 yrs; 68% male; 71% Caucasian; 62% clear cell histology (25% unknown); 1.6 ±0.9 metastatic sites. MSKCC risk was: 28% good, 63% intermediate, 10% poor. Median overall survival (OS) was 12.1 mo (95% CI: 8.7-15.4); median OS by sequence was: No Therapy (n=38; 3.7), mTOR (n=28; 5.2), TKI (n=79; 8.7), mTOR/TKI (n=10; 9.3), TKI/mTOR (n=32; 13.7), TKI/TKI (n=24; 20.7), Other (n=20; 22.5), TKI/mTOR/TKI (N=14; 29.8), TKI/TKI/mTOR (N=10; 33.1). Cox regression identified subgroups with differential outcomes. After significant covariates were controlled, compared with No Therapy, all regimens with TKI as 1st exposure had hazard ratios (HR) <1.0 (range=0.14 – 0.51; all p values ≤ 0.02). Other treatment had HR=0.31 (P=0.001), but when mTOR was the only treatment HR=1.04 (p=0.88). MSKCC scores of intermediate (HR=2.4) or poor (HR=4.5) were a significant risk (p<0.001). Conclusions: Only pts treated with two TKI exposures (≥20.7 mo) approached the best OS seen in trials (26 mo). For mTOR only, 1st line treatment in sicker patients, OS (5.2 mo) was shorter than trials (11 mo). Outcome differences between trial and community practice settings offer insights into opportunities to optimize care.
This study assesses resource utilization and total direct medical cost among patients in the United States starting systemic antineoplastic therapy (ST) pre- and postapproval of immuno-oncology (IO) agents for advanced non-small cell lung cancer. Adults diagnosed with lung cancer initiating first-line ST within 6 months of diagnosis during either the pre- (March 2013-March 2014) or post-IO (March 2015-December 2016) approval period were identified in a US-based multipayer administrative claims database. Excluded were patients with small cell lung cancer, secondary malignancies, less than 1 month follow-up, and those in clinical trials. Total cost (TC) was calculated from the date of initiation of treatment until the last follow-up. Propensity score matching was adjusted for differences in patient cohorts, including follow-up time. Binary multiple logistic regression assessed predictors of high TC (above mean) pre- and post IO. Mean TC per patient was higher pre-IO versus post IO in both unmatched ($165,548 vs $95,715) and matched analyses($129,977 vs $113,177). Hospitalization and emergency department (ED) visit rates were higher pre-IO versus postapproval. Predictors of high TC pre-IO included use of first-line combination therapy, radiation, targeted therapy, maintenance therapy, biomarker testing, more comorbidities, longer follow-up, first-line hospitalization, first-line cost above mean, and age 65 years and older. In the post-IO period, additional predictors of higher TC included use of IO, having mild liver disease or hemiplegia, and longer time to ST initiation. Early data show lower ED visit and hospitalization rates and associated lower TC in the post-IO era.
