Dynamic Changes of Health Utility in Lung Cancer Patients Receiving Different Treatments: A 7-Year Follow-up.

INTRODUCTION: This study aimed to estimate the utility values of all subtypes of lung cancer. The trajectories after different kinds of treatments and their major determinants were explored on the basis of real-world data and repeated measurements. METHODS: From 2011 to 2017, all patients with lung cancer who visited a medical center were invited to fill out the EuroQol Five-Dimension and WHO Quality of Life-Brief questionnaires at each visit. Utility values of quality of life (QoL) after diagnosis and treatments were depicted using a kernel smoothing method. We constructed linear mixed models to predict health utility in each time period and cross-validated them with domain scores of the WHO Quality of Life-Brief. RESULTS: A total of 1715 patients were enrolled, with 6762 QoL measurements. Utility values were lower in patients with advanced-stage disease and older patients. Patients receiving second-line targeted therapy showed higher utility values at 0 to 3 months, 3 to 6 months, and 6 months and beyond (0.89, 0.90, and 0.88, respectively) than did those undergoing chemotherapy (0.81, 0.85, and 0.80, respectively). After using mixed models to control confounders, including poor performance status and disease progression, patients receiving second-line chemotherapy showed health utility similar to that at quasi-baseline, whereas utility values related to second-line targeted therapy were higher at 3 to 6 months and 6 months and beyond (ß = 0.07, p = 0.010 and ß = 0.07, p < 0.001, respectively). There was convergent validity between the utility values and scores of the physical and psychological domains. CONCLUSION: Targeted therapy provided treated patients with a higher health utility value than was provided to those treated with chemotherapy. Development of the longitudinal trajectory may help predict changes in QoL and improve the care of lung cancer survivors.

Comparative Survival Associated With Use of Targeted vs Nontargeted Therapy in Medicare Patients With Metastatic Renal Cell Carcinoma.

Importance: Targeted therapies for advanced renal cell carcinoma (RCC) have shown increased tolerability and survival advantages over older treatments in clinical trials, but understanding of real-world survival improvements is still emerging. Objective: To compare overall and RCC-specific survival associated with use of targeted vs nontargeted therapy for metastatic RCC. Design, Setting, and Participants: This retrospective cohort study used Surveillance, Epidemiology, and End Results-Medicare data from 2000 to 2013 to examine patients with stage IV (distant) clear cell RCC at the time of diagnosis who received any targeted or nontargeted therapy. A 2-stage residual inclusion model was fitted to estimate the survival advantages of targeted treatments using an instrumental variable approach to account for both measured and unmeasured group differences. Data analyses were conducted from July 24, 2017, to April 4, 2019. Exposures: Targeted therapy (study group) or nontargeted therapy (control group). Main Outcomes and Measures: Overall survival and RCC-specific survival, defined as the interval between the date of first drug treatment and date of death or end of the observation period. Results: The final sample included 1015 patients (mean [SD] age, 71.2 [8.1] years; 392 [39%] women); 374 (37%) received nontargeted therapy and 641 (63%) received targeted therapy. The targeted therapy group had a greater percentage of disabled patients (ie, those <65 years old who were eligible for Medicare because of disability) and older patients (ie, those ≥75 years old) and higher comorbidity index and disability scores compared with the nontargeted therapy group. Unadjusted Kaplan-Meier survival curves showed higher overall survival for targeted vs nontargeted therapy (log-rank test, χ21 = 5.79; P = .02); median survival was not statistically significantly different (8.7 months [95% CI, 7.3-10.2 months] vs 7.2 months [95% CI, 5.8-8.8 months]; P = .14). According to the instrumental variable analysis, the median overall survival advantage was 3.0 months (95% CI, 0.7-5.3 months), and overall survival improvements associated with targeted therapy vs nontargeted therapy were statistically significant: 8% at 1 year (44% [95% CI, 39%-50%] vs 36% [95% CI, 30%-42%]; P = .01), 7% at 2 years (25% [95% CI, 20%-30%] vs 18% [95% CI, 13%-23%]; P = .009), and 5% at 3 years (15% [95% CI, 11%-19%] vs 10% [95% CI, 6%-13%]; P = .01). Receipt of targeted therapy was associated with a lower hazard of death compared with nontargeted therapy (overall survival hazard ratio, 0.78 [95% CI, 0.65-0.94]; RCC-specific survival hazard ratio, 0.77 [95% CI, 0.62-0.96]). Conclusions and Relevance: Targeted therapies were associated with modest survival advantages despite a treatment group with more medical complexity, likely reflecting appropriateness for an expanded population of patients. As advances in cancer treatment continue, rigorous methods that account for unobserved confounders will be needed to evaluate their real-world impact on outcomes.

Update of survival and cost of metastatic melanoma with new drugs: Estimations from the MelBase cohort.

PURPOSE: Since 2011, significant progress was observed in metastatic melanoma (MM), with the commercialisation of seven immunotherapies or targeted therapies, which showed significant improvement in survival. In France, in 2004, the cost of MM was estimated at €1634 per patient; this cost has not been re-estimated since. This study provided an update on survival and cost in real-life clinical practice. METHODS: Clinical and economic data (treatments, hospitalisations, radiotherapy sessions, visits, imaging and biological exams) were extracted from the prospective MelBase cohort, collecting individual data in 955 patients in 26 hospitals, from diagnosis of metastatic disease until death. Survival was estimated by the Kaplan-Meier method. Costs were calculated from the health insurance perspective using French tariffs. For live patients, survival and costs were extrapolated using a multistate model, describing the 5-year course of the disease according to patient prognostic factors and number of treatment lines. RESULTS: Since the availability of new drugs, the mean survival time of MM patients has increased to 23.6 months (95%confidence interval [CI] :21.2;26.6), with 58% of patients receiving a second line of treatment. Mean management costs increased to €269,682 (95%CI:244,196;304,916) per patient. Drugs accounted for 80% of the total cost. CONCLUSION: This study is the first that evaluated the impact of immunotherapies and targeted therapies both on survival and cost in real-life conditions. Alongside the introduction of breakthrough therapies in the first and subsequent lines, MM has been associated with a significant increase in survival but also in costs, raising the question of financial sustainability.

Strategies For Clinical Implementation: Precision Oncology At Three Distinct Institutions.

Despite rapid advances in molecular diagnostics and targeted therapeutics, the adoption of precision medicine into clinical oncology workflows has been slow. Questions about clinical utility, inconsistent reimbursement for molecular diagnostics, and limited access to targeted therapies are some of the major hurdles that have hampered clinical adoption. Despite these challenges, providers have invested in precision medicine programs in an ongoing search for innovative care models to deliver improved patient outcomes and achieve economic gains. We describe the precision oncology medicine programs implemented by an integrated delivery system, a community care center, and an academic medical center, to demonstrate the approaches and challenges associated with clinical implementation efforts designed to advance this treatment paradigm. Payer policies that include coverage for broad genomic testing panels would support the broader application of precision medicine, deepen research benefits, and bring targeted therapies to more patients with advanced cancer.

Real-world utilization of molecular diagnostic testing and matched drug therapies in the treatment of metastatic cancers.

AIMS: To assess the frequency of biopsies and molecular diagnostic testing (human DNA/RNA analysis), anti-cancer drug use (genomically-matched targeted therapy [GMTT], unmatched targeted therapy [UTT], endocrine therapy [ET], and chemotherapy [CT]), and medical service costs among adults with metastatic cancer. METHODS: Adults diagnosed with metastatic breast, non-small cell lung (NSCLC), colorectal, head and neck, ovarian, and uterine cancer (2010Q1-2015Q1) were identified in the OptumHealth Care Solutions claims database and followed from first metastatic diagnosis for ≥1 month and until the end of data availability. Utilization was assessed for each cancer cohort (all and patients aged ≥65 years); per-patient-per-month (PPPM) medical service costs were assessed for all patients. Testing frequency estimates were applied to Surveillance, Epidemiology, and End Results Program data to estimate the number of untested patients (2010-2014). RESULTS: Patients with metastatic cancer (n = 8,193; breast [n = 3,414], NSCLC [n = 2,231], colorectal [n = 1,611], head and neck [n = 511], ovarian [n = 275], and uterine [n = 151]) were 63 years old (mean), with 11.1-22.2 months of observation. Biopsy and molecular diagnostic testing frequencies ranged from 7% (uterine) to 73% (ovarian), and from 34% (head and neck) to 52% (breast), respectively. Few were treated with GMTT (breast, 11%; NSCLC, 9%; colorectal, 6%). Treatment with UTT ranged from 0.7% (uterine) to 21% (colorectal). Biopsy, diagnostic testing, and anti-cancer drug therapy were less frequent for those ≥65 years. Medical service costs (PPPM, mean) ranged from $6,618 (head and neck) to $9,940 (ovarian). The estimated number of untested new patients with metastatic cancer was 636,369 (all) and 341,397 (≥65). LIMITATIONS: In addition to the limitations of claims analyses, diagnostic testing frequency may be under-estimated if patients underwent testing prior to study inclusion. CONCLUSIONS: The low frequency of molecular diagnostic testing suggests there are opportunities to better inform management of patients with advanced cancer, particularly decisions to treat with GMTT.

Association of high cost sharing and targeted therapy initiation among elderly Medicare patients with metastatic renal cell carcinoma.

High out-of-pocket costs may limit access to oral therapies covered by patients' prescription drug benefits. We explored financial barriers to treatment initiation in patients newly diagnosed with metastatic renal cell carcinoma (mRCC) by comparing Medicare Part D patients with low out-of-pocket costs due to receipt of full low-income subsidies (LIS beneficiaries) to their counterparts who were responsible for more than 25% cost sharing during Medicare's initial coverage phase (non-LIS beneficiaries). We used 2011-2013 100% Medicare claims for non-LIS and LIS beneficiaries newly diagnosed with metastases in the liver, lung, or bone to examine targeted therapy treatment initiation rates and time to initiation for (1) oral medications (sorafenib, sunitinib, everolimus, pazopanib, or axitinib) covered under Medicare's prescription drug benefit (Part D); (2) injected or infused medications (temsirolimus or bevacizumab) covered by Medicare's medical benefit (Part B); and (3) any (Part D or Part B) targeted therapy. The final sample included 1721 patients. On average, non-LIS patients were responsible for out-of-pocket costs of ≥$2,800 for their initial oral prescription, as compared to ≤$6.60 for LIS patients. Compared to LIS patients, a lower percentage of non-LIS patients initiated oral therapies (risk-adjusted rates, 20.7% vs. 33.9%; odds ratio [OR] = 0.49, 95% CI: 0.36-0.67, P < 0.001) and any targeted therapies (26.7% vs. 40.4%, OR = 0.52, 95% CI: 0.38-0.71, P < 0.001). Non-LIS patients were also slower to access therapy. High cost sharing was associated with reduced and/or delayed access to targeted therapies under Medicare Part D, suggesting that financial barriers play a role in treatment decisions.

[Social medicine assessment after surgical and targeted treatment of renal cell cancer]. / Sozialmedizinische Begutachtung nach operativer und zielgerichteter Therapie des Nierenzellkarzinoms.

In Germany, renal cell cancer counts for 2.5 % of all carcinomas in women and 3.5 % in men. Curative therapy ensures good chances of recovery. But there might be permanent complications like renal insufficiency, pain, incisional hernia, flank muscle relaxation, and paresis. In addition, targeted therapy is associated with several potential side effects. In both therapy groups, severe psychological problems may occur. Still employed patients with these problems must be examined by an expert to estimate the possibilities of returning to working (positive scope of work) and occupations which can not be performed anymore (negative scope of work).

Longitudinal trends in use of targeted therapies for treatment of malignant neoplasms of the eye: a population-based study in Taiwan.

OBJECTIVES: This study examined the recent trend in use and costs of antineoplastic agents for treatment of eye malignancies in Taiwan from 2009 to 2012. We also forecasted use and costs of targeted therapies up to and including year 2016 based on the current patterns. DESIGN: Retrospective observational study focusing on the usage of targeted therapies for treatment of eye malignancy. SETTING: The monthly claims data for eye malignancy-related antineoplastic agents were retrieved from Taiwan's National Health Insurance Research Database (2009-2012). MAIN OUTCOME MEASURES: We calculated the number of prescriptions and costs for each class of medications, and analysed their time trends. In addition, using a time series design with ARIMA models, we estimated the market share by prescription volume and the proportion of costs for targeted therapies for year 2016. RESULTS: The market share by prescription volume of targeted therapies grew from 1.56% in 2009 to 9.98% in 2012 among all antineoplastic agents, and the proportion of costs for targeted therapies rose from 15.12% in 2009 to 58.88% in 2012. Especially, the proportion of costs for protein kinase inhibitors grew from 25.62% to 45.28% among all antineoplastic agents between 2010 and 2012. The market share by prescription volume and the proportion of costs for targeted therapies for treatment of eye malignancies were predicted to reach 27.33% and 91.39% by the fourth quarter in 2016, respectively. CONCLUSIONS: This is the first study that examined and forecasted use and costs of targeted therapies for treatment of eye malignancies in Taiwan. Our findings indicate that, compared with other classes of drugs, targeted therapies are having a more and more relevant share among all treatment strategies for eye malignancies in Taiwan, and due to their high costs they are likely to cause great economic burden.

Disparities in Use of Human Epidermal Growth Hormone Receptor 2-Targeted Therapy for Early-Stage Breast Cancer.

PURPOSE: Trastuzumab is a key component of adjuvant therapy for stage I to III human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The rates and patterns of trastuzumab use have never been described in a population-based sample. The recent addition of HER2 information to the SEER-Medicare database offers an opportunity to examine patterns of trastuzumab use and to evaluate possible disparities in receipt of trastuzumab. METHODS: We examined a national cohort of Medicare beneficiaries with incident stage I to III HER2-positive breast cancer diagnosed in 2010 and 2011 (n = 1,362). We used insurance claims data to track any use of trastuzumab in the 12 months after diagnosis as well as to identify chemotherapy drugs used in partnership with trastuzumab. We used modified Poisson regression analysis to evaluate the independent effect of race on likelihood of receiving trastuzumab by controlling for clinical need, comorbidity, and community-level socioeconomic status. RESULTS: Overall, 50% of white women and 40% of black women received some trastuzumab therapy. Among women with stage III disease, 74% of whites and 56% of blacks received trastuzumab. After adjustment for tumor characteristics, poverty, and comorbidity, black women were 25% less likely to receive trastuzumab within 1 year of diagnosis than white women (risk ratio, 0.745; 95% CI, 0.60 to 0.93). CONCLUSION: Approxemately one half of patients 65 years of age and older with stage I to III breast cancer do not receive trastuzumab-based therapy, which includes many with locally advanced disease. Significant racial disparities exist in the receipt of this highly effective therapy. Further research that identifies barriers to use and increases uptake of trastuzumab could potentially improve recurrence and survival outcomes in this population, particularly among minority women.

Connecticut's Value-Based Insurance Plan Increased The Use Of Targeted Services And Medication Adherence.

In 2011 Connecticut implemented the Health Enhancement Program for state employees. This voluntary program followed the principles of value-based insurance design (VBID) by lowering patient costs for certain high-value primary and chronic disease preventive services, coupled with requirements that enrollees receive these services. Nonparticipants in the program, including those removed for noncompliance with its requirements, were assessed a premium surcharge. The program was intended to curb cost growth and improve health through adherence to evidence-based preventive care. To evaluate its efficacy in doing so, we compared changes in service use and spending after implementation of the program to trends among employees of six other states. Compared to employees of other states, Connecticut employees were similar in age and sex but had a slightly higher percentage of enrollees with chronic conditions and substantially higher spending at baseline. During the program's first two years, the use of targeted services and adherence to medications for chronic conditions increased, while emergency department use decreased, relative to the situation in the comparison states. The program's impact on costs was inconclusive and requires a longer follow-up period. This novel combination of VBID principles and participation requirements may be a tool that can help plan sponsors increase the use of evidence-based preventive services.

Racial Variation in the Uptake of Oncotype DX Testing for Early-Stage Breast Cancer.

PURPOSE: Oncotype DX (ODX) is a tumor gene-profiling test that aids in adjuvant chemotherapy decision-making. ODX has the potential to improve quality of care; however, if not equally accessible across racial groups, disparities in cancer care quality may persist or worsen. We examined racial disparities in ODX testing uptake. METHODS: We used data from the Carolina Breast Cancer Study, phase III, a longitudinal, population-based study of 2,998 North Carolina women who received a diagnosis of breast cancer between 2008 and 2014. Our primary analysis used modified Poisson regression to determine the association between race and whether ODX testing was ordered among two strata: node-negative and node-positive breast cancer. RESULTS: A total of 1,468 women with estrogen receptor-positive, human epidermal growth factor receptor-2-negative, stage I or II breast cancer met inclusion criteria. Black patients had higher-grade and larger tumors, more comorbidities, younger age at diagnosis, and lower socioeconomic status than non-black women. Overall, 42% of women had ODX test results in their pathology reports. Compared with those who did not receive ODX testing, women who received ODX testing tended to be younger and have medium tumor size and grade. Our regression analyses indicated no racial disparities in ODX uptake among node-negative patients. However, racial differences were detected among node-positive patients, with black patients being 46% less likely to receive ODX testing than non-black women (adjusted relative risk, 0.54; 95% CI, 0.35 to 0.84; P = .006). CONCLUSION: We did not find racial disparities in ODX testing for node-negative patients for whom ODX testing is guideline recommended and widely covered by insurers. However, our findings suggest that a newer, non-guideline-concordant application of ODX testing for node-positive breast cancer was accessed less by black women than by non-black women, reflecting more guideline concordant care among black women.

Scientometrics of drug discovery efforts: pain-related molecular targets.

The aim of this study was to make a scientometric assessment of drug discovery efforts centered on pain-related molecular targets. The following scientometric indices were used: the popularity index, representing the share of articles (or patents) on a specific topic among all articles (or patents) on pain over the same 5-year period; the index of change, representing the change in the number of articles (or patents) on a topic from one 5-year period to the next; the index of expectations, representing the ratio of the number of all types of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed over a 5-year period; the total number of articles representing Phase I-III trials of investigational drugs over a 5-year period; and the trial balance index, a ratio of Phase I-II publications to Phase III publications. Articles (PubMed database) and patents (US Patent and Trademark Office database) on 17 topics related to pain mechanisms were assessed during six 5-year periods from 1984 to 2013. During the most recent 5-year period (2009-2013), seven of 17 topics have demonstrated high research activity (purinergic receptors, serotonin, transient receptor potential channels, cytokines, gamma aminobutyric acid, glutamate, and protein kinases). However, even with these seven topics, the index of expectations decreased or did not change compared with the 2004-2008 period. In addition, publications representing Phase I-III trials of investigational drugs (2009-2013) did not indicate great enthusiasm on the part of the pharmaceutical industry regarding drugs specifically designed for treatment of pain. A promising development related to the new tool of molecular targeting, ie, monoclonal antibodies, for pain treatment has not yet resulted in real success. This approach has not yet demonstrated clinical effectiveness (at least with nerve growth factor) much beyond conventional analgesics, when its potential cost is more than an order of magnitude higher than that of conventional treatments. This scientometric assessment demonstrated a lack of real breakthrough developments.

Does Cancer Literature Reflect Multidisciplinary Practice? A Systematic Review of Oncology Studies in the Medical Literature Over a 20-Year Period.

PURPOSE: Quality cancer care is best delivered through a multidisciplinary approach requiring awareness of current evidence for all oncologic specialties. The highest impact journals often disseminate such information, so the distribution and characteristics of oncology studies by primary intervention (local therapies, systemic therapies, and targeted agents) were evaluated in 10 high-impact journals over a 20-year period. METHODS AND MATERIALS: Articles published in 1994, 2004, and 2014 in New England Journal of Medicine, Lancet, Journal of the American Medical Association, Lancet Oncology, Journal of Clinical Oncology, Annals of Oncology, Radiotherapy and Oncology, International Journal of Radiation Oncology, Biology, Physics, Annals of Surgical Oncology, and European Journal of Surgical Oncology were identified. Included studies were prospectively conducted and evaluated a therapeutic intervention. RESULTS: A total of 960 studies were included: 240 (25%) investigated local therapies, 551 (57.4%) investigated systemic therapies, and 169 (17.6%) investigated targeted therapies. More local therapy trials (n=185 [77.1%]) evaluated definitive, primary treatment than systemic (n=178 [32.3%]) or targeted therapy trials (n=38 [22.5%]; P<.001). Local therapy trials (n=16 [6.7%]) also had significantly lower rates of industry funding than systemic (n=207 [37.6%]) and targeted therapy trials (n=129 [76.3%]; P<.001). Targeted therapy trials represented 5 (2%), 38 (10.2%), and 126 (38%) of those published in 1994, 2004, and 2014, respectively (P<.001), and industry-funded 48 (18.9%), 122 (32.6%), and 182 (54.8%) trials, respectively (P<.001). Compared to publication of systemic therapy trial articles, articles investigating local therapy (odds ratio: 0.025 [95% confidence interval: 0.012-0.048]; P<.001) were less likely to be found in high-impact general medical journals. CONCLUSIONS: Fewer studies evaluating local therapies, such as surgery and radiation, are published in high-impact oncology and medicine literature. Further research and attention are necessary to guide efforts promoting appropriate representation of all oncology studies in high-impact, broad-readership journals.

Towards using a full spectrum of early clinical trial data: a retrospective analysis to compare potential longitudinal categorical models for molecular targeted therapies in oncology.

Following the pattern of phase I clinical trials for cytotoxic drugs, dose-finding clinical trials in oncology of molecularly targeted agents (MTA) aim at determining the maximum tolerated dose (MTD). In classical phase I clinical trials, MTD is generally defined by the number of patients with short-term major treatment toxicities (usually called dose-limiting toxicities, DLT), occurring during the first cycle of study treatment (e.g. within the first 3weeks of treatment). However, S. Postel-Vinay (2011) highlighted that half of grade 3 to 4 toxicities, usually considered as DLT, occur after the first cycle of MTA treatment. In addition, MTAs could induce other moderate (e.g. grade 2) toxicities which could be taken into account depending on their clinical importance, chronic nature and duration. Ignoring these late toxicities may lead to an underestimation of the drug toxicity and to wrong dose recommendations for phase II and III clinical trials. Some methods have been proposed, such as the time-to-event continuous reassessment method (Cheung 2000 and Mauguen 2011), to take into account the late toxicities. We suggest approaches based on longitudinal models (Doussau 2013). We compare several models for longitudinal data, such as transitional or marginal models, to take into account all relevant toxicities occurring during the entire length of the patient treatment (and not just the events within a predefined short-term time-window). These models allow the statistician to benefit from a larger amount of safety data which could potentially improve that accuracy in MTD assessment.

Treatment patterns and survival in metastatic breast cancer patients by tumor characteristics.

OBJECTIVES: Study objectives were to compare the treatment patterns and clinical outcomes among metastatic breast cancer (mBC) patients by receipt of HER2-targeted agents and among subgroups of HER2-targeted agent users. RESEARCH DESIGN AND METHODS: Adult women newly diagnosed with mBC (index date) during 2008-2012 were selected from the Truven MarketScan databases and followed until end of enrollment or inpatient death. Patients with <12 months of data, pre-index primary cancers other than breast cancer, pregnancy, or HIV/AIDS were excluded. Study cohorts were users and nonusers of HER2-targeted agents and women with no treatment; and HER2-targeted agent subgroups by receipt of hormonal therapy (HT), de novo vs. recurrent status, and age group. Pre- and post-index breast cancer treatments were compared across cohorts. Relative risk of progression and death were evaluated among the subset of patients with mortality data. RESULTS: Of 18,059 eligible women selected, 14.6% were users of HER2-targeted agents, 71.1% were nonusers, and 14.3% untreated. HER2-targeted agent users received more aggressive cancer treatments compared to nonusers. HER2-targeted agent users were 33% more likely to progress and had a similar risk of death compared to nonusers. Among HER2-targeted agent subgroups, the risk of progression was 30% lower among HT+ patients vs. HT-, 32% lower for de novo vs. recurrent, and similar across age groups. The risk of death was 52% lower for HT+ vs. HT-, 35% lower for de novo vs. recurrent, and increased with age. LIMITATIONS: Identification of distant metastasis, tumor receptor expression and disease progression were based on claims data rather than on clinical assessment. CONCLUSIONS: Receipt of HER2-targeted agents (vs. non-HER2-targeted agents) was significantly associated with receipt of pre- and post-index breast cancer treatments. HER2-targeted agent users were more likely to progress but had a similar risk of death during follow-up. Among HER2-targeted agent subgroups, HT+ and de novo status were associated with a reduced risk of progression and death.

Multiple myeloma treatment transformed: a population-based study of changes in initial management approaches in the United States.

PURPOSE: Despite improved outcomes for multiple myeloma, little is known about changes in initial treatment at the population level for US patients. We report trends in treatment practices. PATIENTS AND METHODS: Patients (n = 1,976) with newly diagnosed myeloma in 1999, 2003, and 2007 were examined by using the National Cancer Institute's Patterns of Care Studies. We assessed use of common chemotherapies (melphalan, vincristine, and doxorubicin), novel agents (thalidomide, bortezomib, or lenalidomide), or hematopoietic stem-cell transplantation (HSCT) during the first year after diagnosis. By using logistic regression, we evaluated the association of race and insurance status with receipt of high-cost treatments--transplantation or novel agents. RESULTS: From 1999 to 2007, use of melphalan alone dropped from 32.0% to 4.1%, and vincristine and doxorubicin use declined from 18.2% to 0.4%. The percentage of patients receiving any novel agent rose from 3.9% in 1999 to 75.5% in 2007. HSCT increased from 11.1% in 1999 to 21.7% in 2007. For white patients, use of novel agents was lower for those with Medicare only (42.6%) than for those with private insurance (50.2%). For patients of other races, those with Medicare only or Medicaid were less likely to receive novel agents or transplantation compared with those with private insurance. CONCLUSION: Initial treatment for multiple myeloma has changed markedly. Most patients now receive novel agents, with a decline in the use of traditional chemotherapy. Use of transplantation and novel agents varies with race and insurance. These findings document rapid changes in patterns of care and highlight addressable disparities in myeloma care.

The clinical development of molecularly targeted agents in combination with radiation therapy: a pharmaceutical perspective.

This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the clinicaltrials.gov Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, and PubMed databases and then cross-correlated with clinicaltrials.gov protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that such trials are not given priority by pharmaceutical companies. The potential reasons for this and some challenges and possible solutions are discussed.