Jonathan K Kish

Earlier presentation and application of curative treatments in hepatocellular carcinoma

The purpose of the study was to assess the use of curative therapies for hepatocellular carcinoma (HCC) in the population. HCC treatment patterns were examined in Surveillance, Epidemiology, and End Results (SEER) 18 registries (28% of U.S.). Joinpoint regression analyses were performed to assess 2000‐2010 incidence trends by tumor size, count, and receipt of potentially curative treatments (transplantation, resection, and ablation). SEER‐Medicare data enabled evaluation of treatment patterns including receipt of sorafenib or transarterial chemoembolization (TACE) by HCC‐associated comorbidities. Diagnoses of tumors ≤5.0 cm in diameter significantly increased during 2000‐2010, surpassing diagnosis of larger tumors. Overall, 23% of cases received potentially curative treatment. Joinpoint models indicated incidence rates of treatment with curative intent increased 17.6% per year during 2000‐2005, then declined by −2.9% per year during 2005‐2010 (P < 0.001). Among HCC cases with a single tumor ≤5.0 cm and no extension beyond the liver, use of ablative therapy significantly increased during 2000‐2010. Use of invasive surgery for single tumors, regardless of size, significantly increased during the initial years of the decade, then plateaued. The group most likely to receive curative treatment in the SEER‐Medicare cases was patients with one, small tumor confined to the liver (657 of 1,597 cases, 41%), with no difference in treatment by hepatic comorbidity status (P = 0.24). A higher proportion of cases with reported liver‐associated comorbidities were, however, diagnosed with tumors ≤5.0 cm in diameter (1,745 0f 2,464, 71%) compared to patients with no reported comorbidities (996 of 2,596, 38%, P < 0.001). Conclusion: Although more HCC patients were diagnosed with early disease over time, the use of curative treatments in this patient group has recently plateaued. Efforts to identify and treat more eligible candidates for curative therapy could be beneficial. (Hepatology 2014;60:1637–1644)

Racial and Ethnic Disparities in Cancer Survival by Neighborhood Socioeconomic Status in Surveillance, Epidemiology, and End Results (SEER) Registries

INTRODUCTION Reducing cancer disparities is a major public health objective. Disparities often are discussed in terms of either race and ethnicity or socioeconomic status (SES), without examining interactions between these variables. METHODS Surveillance, Epidemiology, and End Results (SEER)-18 data, excluding Alaska Native and Louisiana registries, from 2002 to 2008, were used to estimate five-year, cause-specific survival by race/ethnicity and census tract SES. Differences in survival between groups were used to assess absolute disparities. Hazard ratios were examined as a measure of relative disparity. Interactions between race/ethnicity and neighborhood SES were evaluated using proportional hazard models. RESULTS Survival increased with higher SES for all racial/ethnic groups and generally was higher among non-Hispanic white and Asian/Pacific Islander (API) than non-Hispanic black and Hispanic cases. Absolute disparity in breast cancer survival among non-Hispanic black vs non-Hispanic white cases was slightly larger in low-SES areas than in high-SES areas (7.1% and 6.8%, respectively). In contrast, after adjusting for stage, age, and treatment, risk of mortality among non-Hispanic black cases compared with non-Hispanic white cases was 21% higher in low-SES areas and 64% higher in high-SES areas. Similarly, patterns of absolute and relative disparity compared with non-Hispanic whites differed by SES for Hispanic breast cancer, non-Hispanic black colorectal cancer, and prostate cancer cases. Statistically significant interactions existed between race/ethnicity and SES for colorectal and female breast cancers. DISCUSSION In health disparities research, both relative and absolute measures provide context. A better understanding of the interactions between race/ethnicity and SES may be useful in directing screening and treatment resources toward at-risk populations.

Real-world treatment patterns and associated progression-free survival in relapsed/refractory multiple myeloma among US community oncology practices

ABSTRACT Background: Evidence supporting optimal treatment sequencing in relapsed/refractory multiple myeloma (RRMM) patients requiring multiple therapy lines is lacking. Methods: Using retrospective chart data, this study describes real-world RRMM treatment patterns and related progression-free survival (PFS) in US community oncology clinics. Results: Bortezomib ± a non-immunomodulatory drug (IMiD), lenalidomide ± a non-proteasome inhibitor (PI), bortezomib + an IMiD were the most commonly used regimens in early lines of therapy. Median PFS was similar in 1st (11.1 months) and 2nd line (10.5) and decreased in lines 3 through 5 (3rd: 7.9; 4th: 7.2, 5th: 5.4). Longest PFS (12.5 months) in first line was with bortezomib + ImiD; longest PFS in second line was with lenalidomide ± a non-PI was (13.2 months). Conclusions: Re-treatment with bortezomib was common; novel agents were reserved for later therapy lines. Overall, the observed PFS associated with real-world treatment sequences were shorter than those reported in clinical trials.

Prioritizing US Cervical Cancer Prevention With Results From a Geospatial Model

Purpose To determine if differences in screening and vaccination patterns across the population may accentuate ethnic and geographic variation in future burden of disease. Methods Using Cancer in North America data provided by the North American Association of Central Cancer Registries, county cervical cancer incidence trends from 1995 to 2009 were modeled for the entire United States using ecologic covariates. Rates for health service areas were also modeled by ethnicity. State-level incidence was mapped together with Papanicolaou (Pap) screening, past 3 years (women ≥ 18 years old), and three-dose human papillomavirus (HPV) vaccine coverage (girls 13 to 17 years old) to identify potential priority areas for preventive services. Results US cervical cancer incidence decreased more during the periods 1995 to 1999 and 2000 to 2004 than during the period 2005 to 2009. During these 15 years, the most affected areas became increasingly confined to Appalachia, the lower Mississippi Valley, the Deep South, Texas, and Florida. Hispanic and black women experienced a higher incidence of cervical cancer than both white and Asian and Pacific Islander women during each period. Women in 10 of 17 states/districts with a high incidence (≥ 8.14/100,000) reported low Pap testing (< 78.5%), HPV vaccine coverage (< 33.9%), or both prevention technologies. Conclusion The decline in cervical cancer incidence has slowed in recent years. Access to HPV vaccination, targeted screening, and treatment in affected populations is needed to reduce cervical cancer disparities in the future.

Estimating the Economic Impact of Adding Panobinostat to a U.S. Formulary for Relapsed and/or Refractory Multiple Myeloma: A Budget Impact and Cost-Benefit Model

BACKGROUND Multiple myeloma is an incurable B-cell malignancy with a natural history that involves alternating periods of remission and subsequent relapse. For relapsed and/or refractory multiple myeloma (RRMM), the typical patient currently receives more lines of therapy than has been feasible in the past, translating into longer progression-free survival (PFS). Consequently, cost issues have become more prominent because patients may be offered newer and more expensive therapies during a more prolonged overall treatment course. OBJECTIVE To estimate the economic impact of adding panobinostat to a U.S. health plan formulary as a treatment option with bortezomib and dexamethasone for patients with RRMM previously treated with a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), using a budget impact and cost-benefit model. METHODS Total costs of commonly used salvage therapy regimens were combined with market share data and population prevalence estimates of RRMM to yield the total cost of treatment, from the perspective of a U.S. third-party payer (commercial or Medicare) with a time horizon of 1 year. Comparator treatment regimens included bortezomib-dexamethasone, lenalidomide-dexamethasone, lenalidomide-bortezomib-dexamethasone, carfilzomib monotherapy, carfilzomib-lenalidomide-dexamethasone, and pomalidomide-dexamethasone. Costs (2015 U.S. dollars) included drug costs for oral oncology agents, medical and administration costs for injectable oncology agents, costs of adverse event (AE) prophylaxis and monitoring, and costs of grade 3/4 AEs. RESULTS In a hypothetical health plan with 1 million members, the annual number of RRMM patients with previous PI and IMiD treatments was estimated at 16 and 118 for a commercial and Medicare plan, respectively. Introduction of panobinostat as part of the panobinostat-bortezomib-dexamethasone regimen was not expected to result in a substantial budget impact to either commercial or Medicare plans, with an incremental cost <

Real-world evidence (RWE) to show improved time to progression among resected pancreatic cancer (RPC) patients receiving adjuvant chemotherapy (adjch).

0.01 per member per month. Panobinostat-bortezomib-dexamethasone had a low cost per treated patient per month without progression, owing to the minimal increase in expenditure over existing bortezomib-based regimens and long median PFS, compared with median duration of treatment. CONCLUSIONS Adding panobinostat to a plan formulary as a treatment option is expected to be cost neutral (and potentially cost saving in the context of new and more expensive treatment regimens). With a low cost per month without progression, panobinostat-bortezomib-dexamethasone represents good value for the money. DISCLOSURES Funding for this study was sponsored by Novartis, East Hanover, New Jersey. Bloudek and Kish are employees of Xcenda, a consulting company contracted by Novartis to conduct this analysis. Roy, Globe, and Kuriakose are employees of Novartis. Siegel is on the advisory boards and speakers bureau of Celgene, Onyx/Amgen, Millennium/Takeda, and Novartis and is on the advisory boards of Merck. Jagannath is a consultant to Sanofi, Bristol-Meyers Squibb, and Celgene. Orloski is a contractor to Xcenda and provided medical writing support, which was funded by Novartis. Study design and concept were contributed by Bloudek, Roy, and Kish, assisted by Globe. Bloukek took the lead in data collection, along with Kish, and data interpretation was performed by Siegal, Jagannath, Globe, and Kuriakose. The manuscript was written primarily by Orloski, along with Roy and Kish, and revised by Roy, along with Siegal, Jagannath, Globe, Orloski, and Kuriakose.

Opioid Use Among Metastatic Prostate Cancer Patients With Skeletal-related Events

242Background: Two recent clinical trials (IMPRESS and APACT) suggest the overall survival (OS) of patients with resected pancreatic cancer (RPC) is far longer than previously believed. Improvements in patient selection, intra/post-operative surgical care adjch are suggested as explanations for the improved OS. RWE of time to progression (TTP) from surgery were calculated to assess if the results of these trials are generalizable. Methods: RPC patients (ICD-9=157.x, excluding 157.4; CPT=48140, 48146, 48150, 48152-5) diagnosed between 03/2012-06/2015 were selected from the Inovalon More2 administrative claims database. Adjch was defined as initiating chemotherapy within 90 days of surgery. TTP was the time from surgery until the first claim for metastatic disease (ICD-9 =196.0-.3, .5-.6, 197.0-.8, 198.0-.8) using the Kaplan-Meier method. Patients without a metastatic diagnosis during their follow-up were censored at 12 months to adjust for underreporting of metastatic disease codes in claims. Results: 1,01...

Disconnect between earlier presentation patterns and application of curative treatments in HCC.

PURPOSE The development of skeletal-related events (SREs) (pathologic fracture, need for surgery and/or radiation to bone, spinal cord compression, and hypercalcemia of malignancy) in metastatic prostate cancer (MPC) is associated with worsened pain and compromised quality of life. Opioids are frequently used throughout the course of SRE treatment. This study describes the treatment patterns and incremental use of opioids in MPC patients diagnosed with SREs. METHODS PC patients with bone metastases newly diagnosed with an SRE between January 1, 2005, and September 30, 2014, were identified using MarketScan Commercial and Medicare databases. Included patients were aged ≥40 years, had medical/pharmacy benefits for ≥12 months before (preindex) and ≥6 months after (postindex) diagnosis, and were without evidence of other primary cancers. Patients were categorized as nonusers of opioids (<10 days), short-term users (≥10 and <60 days), or long-term users (≥60 days) and further by SRE type. Opioid type, proportion of time on opioids, morphine-equivalent dose, adjuvant medications, and radiation use before and after SRE diagnosis were evaluated. FINDINGS A total of 1071 eligible patients were identified (mean age, 71 years; 10.8% had chronic pain at baseline). The most common SRE types present were radiation (60.2%), radiation and bone surgery (15.0%), pathologic fracture (7.2%), and bone surgery (6.5%). Opioid use increased from 49.9% preindex to 53.3% postindex (P < 0.0001). The proportion of time on opioids doubled after SRE (pre, 0.3 vs post, 0.6; P < 0.0001). A greater percentage of patients used only opioids after an SRE (pre, 11.0%; post, 46.1% [P < 0.0001]), while a lesser percentage of patients used only radiation after an SRE (pre, 36.0%; post, 4.7% [P < 0.0001]). An increase was observed in patients using neither radiation nor opioids (pre, 14.5%; post, 42.0% [P < 0.0001]). An increase of ~50% was noted in long-term opioid users (from 22.1% to 32.1%). The use of monotherapy with a short-acting opioid decreased (pre, 35.1%; post, 32.5% [P < 0.0001]), while use of mixed opioids increased (pre, 13.7%; post, 19.1% [P < 0.0001]). Mean morphine-equivalent dose increased from pre- to post-SRE (9.1 vs 13.1 mg). Bisphosphonate and NSAID users decreased from before to after an SRE diagnosis (bisphosphonates, 40.2% vs 8.6%; NSAIDs, 26.7% vs 17.5% [both, P < 0.0001]). IMPLICATIONS Long-term opioid use and dose were significantly increased after SRE development in MPC. The high percentage of patients not treated with an opioid or radiation potentially supports the need for additional treatment options for controlling pain if medically necessary and/or to prevent SREs.

Objective response rate (ORR) and time to treatment failure (TTF) for BRAF v600 mutated metastatic melanoma (BRAF+ MM) patients receiving first-line (1L) targeted therapy (TT) or immuno-oncology (I-O) agents at US-based community oncology practices.

187 Background: In the U.S., a greater proportion of small hepatocellular carcinomas are being diagnosed. The extent to which patients with small HCCs are receiving potentially curative therapies is unclear. Methods: Receipt of liver transplantation, resection, radiofrequency ablation, and other or unspecified surgery/ablation as first therapy was examined among HCC cases in the NCI SEER18 cancer registries during the years 2000 to 2010. Survival of HCC by treatment modality was also examined. Results: The diagnosis of small tumors (≤5 cm) significantly increased between 2000 and 2010, surpassing diagnosis of larger tumors beginning in 2005. Among patients diagnosed during 2007-2010 with complete data available, 57% had small tumors and more than three quarters had a single tumor, however fewer than one third received surgical or ablative treatment. Incidence rates of resection, ablation and transplantation (therapies with curative intent) increased 17.6% per year between 2000 and 2005, then decreased by ...