Combination Therapy Of Braf Inhibitors For Advanced Melanoma With V600 Braf Mutation: A Systematic Review And Meta-Analysis

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of completing a successful minimally invasive surgery for anterior rectal resection, without compromising patient safety. Further research is warranted to explore risk factors for and economic outcomes of conversion to OS. PCN19 Metformin Chemoprevention Against Pancreatic Adenocarcinoma In Patients With Type 2 Diabetes Mellitus: Results Of A Disease Simulation Model Jeon A, Pandharipande PV, Kong CY, Hur C Massachusetts General Hospital, Boston, MA, USA

Objectives: Type II diabetes mellitus (T2DM) is associated with an increased risk of pancreatic adenocarcinoma (PAC). Epidemiological evidence indicates that metformin use, a biguanide used as a first-line treatment for diabetes, may decrease the risk of PAC. Our objective was to evaluate metformin chemoprevention in T2DM patients with respect to life expectancy, PAC incidence and mortality, and net difference in quality-adjusted life years (QALYs).  Methods: A previously published state-transition model of PAC was revised to reflect increased all-cause mortality and risk of progression for pancreatic cancer in patients with diabetes. A hypothetical cohort of patients with T2DM for two years or more were treated with metformin starting at age 50 (base case). The primary endpoint was net gain in life expectancy (LE) compared to no treatment. Secondary endpoints included the number needed to treat (NNT) to prevent one PAC incidence, and NNT to prevent one PAC death, and change in QALYs. Sensitivity analyses were performed on key model inputs, including the decreased risk for PAC incidence on metformin, adherence rates to treatment, and quality of life (QoL) changes due to GI side effects.  Results: Treatment with metformin resulted in an overall LE gain of 0.01476 years for diabetic patients, a NNT of 641 to prevent one PAC incidence, and a NNT of 825 to prevent one PAC death, but a decrease in -0.01173 QALYs. The results were sensitive to the decreased PAC risk from taking metformin, adherence rate to the treatment, and disutility of taking metformin.  Conclusions: Metformin led to an increase in LE gained because of reduced cancer deaths but a decrease in QALYs as a result of side effects. Patients may want to weigh both the possible chemopreventive benefits and the possible impact on QoL in treatment decisions. PCN20 Combination Therapy Of Braf Inhibitors For Advanced Melanoma With V600 Braf Mutation: A Systematic Review And Meta-Analysis Kim S, Kim HT, Suh HS Pusan National University, Busan, Korea, The Republic of

Objectives: BRAF inhibitors were approved by US Food and Drug Administration as the treatment of patients with unresectable or metastatic melanoma with the BRAF V600E mutation, opening the era of targeted therapy. As acquired resistance to the BRAF inhibitors became problematic, however, combination strategies were suggested. We conducted a systematic review and meta-analysis to assess the efficacy of combination therapy including BRAF inhibitors as treatment of advanced melanoma with V600 BRAF mutation.  Methods: We searched MEDLINE, EMBASE and The Cochrane Library for randomized controlled trials (RCT), controlled clinical trials (CCT), cohort studies, and case-control studies. The primary outcomes were overall survival (OS) and progression-free survival (PFS) measured in hazard ratio (HR) or median. Secondary outcome was objective response rate (ORR). Using random effects model, we conducted meta-analyses to pool all results.  Results: We identify 5 eligible studies; 4 RCTs and 1 cohort. All five studies used combinations of BRAF inhibitors and MEK inhibitors. Data of 1872 participants were included in meta-analysis. The combined HR of OS was 0.70 (95% CI 0.62 to 0.78) and combined HR of PFS was 0.59 (95% CI 0.55 to 0.63), favoring the combination therapy. In all studies, median overall survival and median progression-free survival were longer in the combination therapy groups. The combined risk ratio of ORR was 1.30 (95% CI 1.20 to 1.40), which means more patients in combination therapy group achieved complete or partial responses than those in monotherapy group.  Conclusions: Combination therapy of BRAF inhibitors and MEK inhibitors significantly improved overall survival, progression-free survival, and objective response rate in advanced melanoma with V600 BRAF mutation. PCN21 Indirect Comparison Of Efficacy Of PonatiniB Versus Bosutinib In 3rd-Line Chronic-Phase Chronic Myeloid Leukemia Using Iterative Proportional Fitting McGarry LJ1, Yang M1, Chiroli S2, Lustgarten S1, Dorer D1 1ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA, 2ARIAD Pharmaceuticals Europe Sàrl, Epalinges, Switzerland

Objectives: Open-label uncontrolled trials of ponatinib (PACE) and bosutinib (NCT00261846; published by Khoury 2012) in CP-CML suggest ponatinib is more efficacious than bosutinib in third-line patients. However, lack of head-to-head randomized trials comparing third-line treatments poses a challenge for clinical and reimbursement decisions. Future trials in third-line CP-CML are unlikely; therefore, to address this evidence gap, we indirectly compared efficacy in PACE versus the bosutinib trial using IPF to adjust for differences in baseline characteristics.  Methods: We examined the subgroup of third-line CP-CML patients in the ponatinib and bosutinib trials, using patient-level data from PACE and the published bosutinib data. IPF was used to reweight the PACE patient-level data so that the reweighted baseline patient characteristics matched the aggregate bosutinib patient characteristics, including gender (male/female), race (white/nonwhite), median age (< 56.0/ ≥ 56.0 years), median time since diagnosis (<  6.7/≥ 6.7 years), ECOG performance status (0/≥ 1), and T315I mutation at study entry (yes/no). The model was fit using maximum likelihood. Efficacy in terms of major (MCyR) and complete (CCyR) cytogenetic response, and major molecular response (MMR) within 12 months are reported. Confidence intervals were simulated by bootstrap resampling of the PACE data.  Results: When reweighted to match bosutinib patient characteristics, the percent of ponatinib patients achieving MCyR (64.1%[ 95% CI: 55.3%-72.9%]), CCyR (52.3% [43.2%-61.5%]) and MMR (38.2% [29.3%-47.1%]) were

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consistent with unadjusted results (MCyR: 64.2%, CCyR: 53.8%, MMR: 43.4%) and exceeded efficacy observed with bosutinib in third-line CP-CML (MCyR: 31.7%, CCyR: 23.1%, MMR: 14.7%). Sensitivity analyses eliminating T315I status from the weighting yielded similar results.  Conclusions: Adjusted ponatinib efficacy outcomes in third-line CP-CML were similar to unadjusted, and efficacy was more than double that observed with bosutinib, irrespective of T315I mutation status. These results suggest that the higher efficacy observed is PACE (ponatinib) versus the bosutinib trial is not due to bias in patient selection. PCN22 Real-World Treatment Patterns And Clinical Outcomes In Er+/ Her2- Metastatic Breast Cancer: Results From A Multicountry Retrospective Medical Record Review Mitra D1, Kurosky S2, Zanotti G1, Kaye JA2 1Pfizer, Inc., New York, NY, USA, 2RTI Health Solutions, Research Triangle Park, NC, USA

Objectives: To describe real-world treatment patterns and key clinical outcomes among postmenopausal patients with estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2−) metastatic breast cancer (MBC) in the United Kingdom, Canada, Belgium, and the Netherlands.  Methods: This was a retrospective study of medical record data from postmenopausal patients treated for ER+/HER2− MBC in four countries. Eligible patients discontinued second-line treatment of metastatic disease between January 1, 2008, and March 1, 2014. Data from all countries were combined to assess patient characteristics, treatment patterns, time to progression (TTP), and progression-free survival.  Results: Information was provided on 438 patients by 107 medical/clinical oncologists. Patients’ mean age was 61.6 years at metastatic diagnosis, and 85.2% were white. The majority of MBC patients had de novo metastatic diagnosis (62.3%); 37.7% progressed from earlier stages. The most common sites of metastasis were bone (66.4%), lung/pleura (47.0%), liver (37.9%), and lymph nodes (34.9%); 69.9% had visceral disease. In the first-line MBC setting, 56.6% of patients received endocrine therapy (ET) alone, 26.0% received chemotherapy (CT) alone, and the remainder received both (in combination [6.4%] or CT followed by ET [11.0%]). During second-line treatment, 32.0% received CT alone, while 5.7% received CT followed by ET. In first-line treatment, 72.4% progressed on or after stopping therapy, with a median TTP of 8.4 months. In second-line treatment, 70.1% progressed, with a median TTP of 6.1 months. Disease progression was the most common reason for discontinuing both first- and second-line treatment (70.1% and 67.1%, respectively).  Conclusions: Although ET is the recommended treatment for most patients with ER+/HER2– MBC, a substantial proportion received CT, possibly due to the high prevalence of visceral disease in the study population. Median TTP on current therapies is <  1 year. These findings suggest a continuing unmet need for new treatments that extend TTP. PCN23 Effectiveness Outcomes In Patients With Advanced Nsclc Treated In Real-World Community Oncology Settings: Results From A Prospective Medical Record Registry Study Walker MS1, Wong W2, Ravelo A2, Hazard S2, Miller PJ1, Schwartzberg L3 Oncology, Memphis, TN, USA, 2Genentech, Inc., South San Francisco, TN, USA, 3The West Clinic, Memphis, TN, USA

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Objectives: A major challenge in the treatment of advanced non-small cell lung cancer (NSCLC) is balancing efficacy and tolerability. We report findings from a prospective medical record (MR) registry that examined treatment effectiveness, toxicity, and patient reported outcomes in patients (pts) newly diagnosed with advanced NSCLC. The focus of this report is progression free survival (PFS), overall survival (OS), and health-related quality of life (HRQOL) through one year of follow-up.  Methods: Pts starting first line treatment of stage IIIB/IV nonsquamous NSCLC were prospectively enrolled and consented at 34 US-based community oncology settings. Eligible pts received one of the following regimens: A: bevacizumab with platinum-based doublet, gemcitabine-based doublet, or pemetrexed and carboplatin; B: platinum or gemcitabine-based doublet without bevacizumab; C: pemetrexed with cisplatin or carboplatin. From the MR, site staff collected baseline characteristics and treatment, toxicity, PFS and OS at 12 months. HRQOL was assessed once per cycle during treatment with the EORTC QLQ-C30 and QLQ-LC13, the MDASI-LC, and the Rotterdam Activity Level Scale (RALS).  Results: Of 155 eligible pts enrolled, 2 died before treatment start and 6 dropped out, leaving 147. Of these, 66 (44.9%) received Regimen A, 25 (17.0%) Regimen B, and 56 (38.1%) Regimen C. 93 pts (63.3%) had at least one adverse event, with no difference in adverse event rate among regimens (p= 0.1955). Regimens did not differ on HRQOL outcomes. Disease progression occurred in 141 pts (95.9%) and death in 102 (69.4%), based on scan records and physician progress notes. Kaplan Meier median first-line PFS was A: 7.4 months, B: 4.2, C: 5.0 (p =  0.0013). Median OS was A: 12.3 months, B: 5.9, C: 7.9 (p < 0.0001).  Conclusions: Bevacizumab-containing regimens were associated with longer PFS and OS, with no significant difference in toxicities or HRQOL compared with other treatments. PCN24 Clinical Characteristics, Treatment Patterns And Health Care Utilization In Er+/Her2- Metastatic Postmenopausal Breast Cancer Patients: Results From A Retrospective Medical Record Review In The United States Zanotti G1, Hunger M2, Perkins JJ1, Horblyuk R1, Martin M3 1Pfizer, Inc., New York, NY, USA, 2Mapi Group, Munich, Germany, 3Mapi Group, Uxbridge, UK

Objectives: As new treatments become available for metastatic breast cancer (mBC), treatment patterns and clinical and economic outcomes may be evolving. To better understand the post-menopausal ER+, HER2- mBC patient population in the US, a medical chart review was conducted.  Methods: A retrospective chart review of 201 post-menopausal patients with confirmed ER+/HER2- mBC treated by 103 medical oncologists or hematologists was conducted between March and April 2015. Patients had to have completed at least 2 lines of therapy in the mBC