Treatment patterns and costs among US patients with diffuse large B-cell lymphoma not treated with 2L stem cell transplantation.

Aim: To assess treatment patterns, healthcare resource utilization (HCRU), and costs for patients with diffuse large B-cell lymphoma (DLBCL) who did not receive stem cell transplantation in second-line. Patients & methods: An administrative MarketScan® database study to assess DLBCL claims from 01/01/2009-30/09/2020. Results: Most patients (n = 750) received rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone in first-line (86.8%) and rituximab (39.5%) or bendamustine ± rituximab ± other (16.3%) in second-line. Over half were hospitalized (mean duration: 16.5 (standard deviation [SD]: 25.8) days per patient per year). Mean medical/pharmacy costs were US$141,532 per patient per year (SD: $189,579), driven by DLBCL-related claims. Conclusion: Healthcare resource utilization and costs for DLBCL-related claims were due to hospitalizations and outpatient visits. Novel therapies to reduce clinical and economic burdens are needed.

Real-world outcomes with immuno-oncology therapies in advanced melanoma: final results of the OPTIMIzE registry study.

Aim: The OPTIMIzE registry study evaluated real-world outcomes in patients with advanced melanoma receiving immuno-oncology therapies. Materials and methods: Data were collected for patients treated with anti-programmed death 1 (PD-1) monotherapy (nivolumab or pembrolizumab; n = 147) or nivolumab plus ipilimumab (n = 81) from 2015-2017 and followed for ≥3 years. Results: Nivolumab plus ipilimumab versus anti-PD-1 monotherapy was associated with a nonsignificantly lower risk of death (adjusted HR: 0.83; 95% CI: 0.54-1.28; p = 0.41), higher disease control rate (72 vs 56%; p = 0.04), and stable quality of life, but more grade 3-4 treatment-related adverse events (54 vs 26%; p < 0.0001). Conclusion: These results support the use of immuno-oncology therapy in advanced melanoma.

Melanoma is a serious form of skin cancer that develops from melanocytes, which are pigment cells that give the skin, hair, and other tissues their color. At advanced stages of spread, melanoma can be life-threatening. However, immunotherapy, a type of therapy that helps the body's immune system to destroy cancer cells, allows some patients with advanced melanoma to live longer. The OPTIMIzE study looked at how well patients with advanced melanoma did when treated with different immunotherapies. These patients were treated in a real-world setting, such as a doctor's office, and were not participating in a clinical trial. Compared with clinical trials, real-world studies like the OPTIMIzE study may include a more varied group of patients because of the less selective study enrollment requirements. In the OPTIMIzE study, patients were treated with either a single immunotherapy (nivolumab or pembrolizumab alone) or a combination of two immunotherapies (nivolumab plus ipilimumab). Both single and combination immunotherapies were effective and tolerable. Patients receiving nivolumab plus ipilimumab had greater tumor shrinkage than patients receiving nivolumab or pembrolizumab alone, but with more side effects from their treatment. Despite the occurrence of side effects with both single and combination immunotherapies, patients reported that their quality of life remained stable while being treated. The OPTIMIzE study shows that immunotherapy is effective and tolerable for patients with advanced melanoma in the real-world setting. This information may help doctors with selecting treatments for their patients with advanced melanoma. Clinical Trial Registration: NCT02780089 (ClinicalTrials.gov).

Real-world outcomes in metastatic HR+/HER2-, HER2+ and triple negative breast cancer after start of first-line therapy.

Aim: We evaluated outcomes of first-line (1L) treatment of metastatic breast cancer by biomarker subtype in the community setting over the last decade. Methods: Eligible patients (n = 1518) were female, ≥18 years, diagnosed with metastatic breast cancer 2010 or later, had documented HR+/HER2-, HER2+, or triple negative breast cancer (TNBC); and initiated 1L therapy. Kaplan-Meier and Cox methods were used to evaluate 1L real-world progression-free survival and overall survival from start of 1L. Results: TNBC was diagnosed at an earlier stage and had higher tumor grade at initial diagnosis. 1L real-world progression-free survival and overall survival from start of 1L were shorter for TNBC than HR+/HER2- or HER2+. Conclusion: Overall prognosis for patients with metastatic TNBC remains poor, and new therapies are needed to improve clinical outcomes.

What is this article about? This study looked at how well women with metastatic breast cancer did after starting treatment. It compared three groups. The first group had tumors that respond to hormone therapy. The second group had tumors that respond to treatment that works on a specific protein. A third group had tumors that don't respond to either of those ­ called triple negative. The study looked at women 18 and older who had metastatic breast cancer in 2010 or later. They had all been treated at a community oncology practice. We looked at how long it took for the cancer to get worse, and how long until patients died, for each of the three groups. What were the results? There were 1518 patients in the study. Most (62.5%) were in the group that responds to hormone therapy. The rest had tumors that respond to treatment that works on the specific protein (23.4%), or had triple negative tumors (14.1%). Patients with triple negative tumors were diagnosed earlier, but they had worse tumor characteristics. They also had shorter time until their cancer got worse, and they did not live as long, compared with the other groups. What do the results of the study mean? This builds on other studies by showing that, even in a modern era, outcomes are poor for patients with triple negative breast cancer. It shows that new treatments are needed for patients with triple negative breast cancer.

Neoadjuvant treatment and survival outcomes by pathologic complete response in HER2-negative early breast cancers.

Background: The benefit of pathologic complete response (pCR) in early breast cancer (eBC) is not well described in the real-world setting. This study used the nationwide Flatiron Health electronic health record-derived deidentified database to describe treatment patterns and survival outcomes by pCR status after neoadjuvant therapy (NAT) in women with triple-negative or HR+/HER2- eBC. Materials & methods: Observational cohort study analyzing women with eBC who started NAT between 2011 and 2018. Results: 496 women were included in the study; of those, 16.1% achieved pCR, of which 35.7% were triple-negative and 6.1% were HR+/HER2- eBC. More women with triple-negative eBC (95.2%) were exclusively treated with chemotherapy-based NAT versus HR+/HER2- eBC (56.1%). In multivariate analyses from NAT start, not achieving pCR was associated with increased risk of death and progression. Conclusion: pCR status may be a reliable prognostic indicator for survival in these eBC subtypes in the real-world setting.

Response to treatment before surgery indicates better outcomes in breast cancer patients. To understand how well cancer treatments work, patients are compared on their overall survival. This measures the number of people in a study or treatment group who are still alive after a certain amount of time from when they were diagnosed or started treatment. Overall survival shows how well patients are doing in their cancer journey, but it takes time to understand how good treatments are when using this measure. In women with early-stage breast cancer, a quicker way to understand how well patients react to their treatment is called pathologic complete response (pCR). Some people have whole-body treatments such as chemotherapy before surgery (known as neoadjuvant treatment). For these patients, pCR may occur after neoadjuvant treatment, meaning all signs of cancer are gone when they have surgery. In real-life clinical settings, little research has been done to understand how pCR can measure breast cancer survival. In this study, the authors investigate whether women who had a pCR were more or less likely to have their cancer become worse or experience death than those who did not achieve pCR. The health records of 496 women diagnosed with early breast cancer over an eight-year period were assessed. The results show that women who did not have a pCR were more likely to have their cancer become worse or die. This means that pCR could be a better way than overall survival to identify which treatments work well in early breast cancer, and importantly, change the course of a patient's journey.

Overall survival in the real-world and clinical trials: a case study validating external controls in advanced melanoma.

Aims: We assessed the suitability of real-world data (RWD) as an external control for analysis of overall survival (OS) compared with clinical trial data (CTD) in advanced melanoma. Methods: OS among adults receiving ipilimumab for advanced melanoma was compared between trials (CTD group) and the Flatiron Health database (RWD group) using Cox models. Adjusted analyses accounted for differences in baseline factors; missing data were addressed through multiple imputation. Results: After adjusting for baseline factors and accounting for missingness, OS was similar in the CTD (n = 241) versus RWD groups (n = 816; hazard ratio: 0.98; 95% CI: 0.75-1.26). Conclusion: Flatiron Health data is suitable to construct external control groups for OS in advanced melanoma trials after adjusting for baseline factors and missing data.

Clinical trials are the gold standard for measuring the efficacy and safety of new treatments. Comparisons between clinical trials and external controls drawn from real-world data are potentially valuable ­ especially when randomized trials are not available or feasible ­ but carry important risks of bias stemming from differences across populations, care settings and measurement of patient characteristics and outcomes. As a case study, we assessed the suitability of a particular real-world database (the Flatiron Health Database) for analyzing overall survival among patients in clinical trials of treatments for metastatic melanoma. Challenges included differences in patient baseline prognostic factors across populations, including high proportions with missing information in real-world data. After accounting for these differences, we observed similar survival between patients receiving ipilimumab monotherapy in clinical trials and in real-world data. We conclude that real-world external controls can be suitable for metastatic melanoma.

Adverse events and clinical outcomes in patients treated with PD-(L)1 blockade for advanced non-small-cell lung cancer.

Aims: To describe, in patients with advanced/metastatic non-small-cell lung cancer, the relationship between baseline immunosuppressive drug (ISD)/corticosteroid (CS) use, as well as the incidence of mild/moderate adverse events (AEs), and the clinical effectiveness of PD (L)-1 blockade. Patients & methods: This was a retrospective cohort study of patients with no evidence (n = 131) or positive evidence (n = 269) of ISD/CS use. Results: Duration of treatment, time to next treatment, progression-free survival and overall survival were significantly reduced for patients with evidence of prior ISD/CS use. Occurrence of mild/moderate AEs did not affect any clinical outcomes. Conclusion: Prior ISD/CS use was associated with a poorer prognosis in advanced/metastatic non-small-cell lung cancer patients treated with PD-(L)1 inhibitors, but the occurrence of AEs had no effect.

What is the article about? Patients with advanced/metastatic non-small-cell lung cancer (aNSCLC) are often treated with a class of drugs known as checkpoint inhibitors. There have been previous reports that treatment with corticosteroids and other drugs that suppress the immune system in the period leading up to treatment with checkpoint inhibitors may result in poorer outcomes, but most of these reports focus on serious adverse events leading to hospitalizations or emergency room visits that result from treatment. This study aimed to determine whether treatment with corticosteroids in these patients had any impact on the occurrence of mild or moderate adverse events and long-term treatment outcomes. What were the results? By looking back at deidentified medical insurance claims from patients with aNSCLC, we found that patients who were treated with corticosteroids or other immunosuppressive drugs (vs those who did not receive these drugs) in the months leading up to treatment with checkpoint inhibitors had poorer treatment outcomes (e.g., shorter overall survival). What do the results of the study mean? This study investigated the real-world outcomes in aNSCLC patients treated with checkpoint inhibitors and found that the use of corticosteroids or other immunosuppressive drugs may have an adverse effect. However, we are unable to rule out the possibility that there was an underlying difference between these two sets of patients that caused the difference in treatment outcomes. Further studies with larger sample sizes are needed.

Real-World Effectiveness of Nivolumab Monotherapy After Prior Systemic Therapy in Advanced Non-Small-Cell Lung Cancer in the United States.

BACKGROUND: In phase 3 clinical trials, nivolumab prolonged overall survival (OS) compared to chemotherapy in patients with previously treated advanced non-small-cell lung cancer (NSCLC). This retrospective real-world study evaluated OS in patients receiving nivolumab for previously treated advanced NSCLC primarily in US community hospitals. PATIENTS AND METHODS: Patient data were taken from electronic health records in the Flatiron Health oncology database. OS was evaluated in patients receiving nivolumab monotherapy for nonsquamous or squamous advanced NSCLC after prior chemotherapy; subgroup analyses were performed by Eastern Cooperative Oncology Group performance status (ECOG PS), age, and other baseline characteristics. Cox analysis was used to determine OS predictors. RESULTS: Of 3019 included patients, 1968 (65%) had nonsquamous and 1051 (35%) had squamous histology. In both cohorts, approximately 20% of patients had a verified ECOG PS ≥ 2, and > 25% were aged ≥ 75 years. For all patients, median OS in the nonsquamous and squamous cohorts was 8.6 months (95% confidence interval [CI], 8.0-9.3) and 7.4 months (95% CI, 6.8-8.5), respectively; for those with ECOG PS 0-1, median OS was 10.8 months (95% CI, 9.8-11.8) and 8.7 months (95% CI, 7.6-9.7), respectively. In both cohorts, programmed death ligand 1 expression ≥ 1% and ECOG PS 0-1 were associated with longer OS (P < .05); the number of prior lines of therapy and age ≥ 75 years had no significant association with OS. CONCLUSIONS: This study confirmed the effectiveness of nivolumab monotherapy for previously treated advanced NSCLC in real-world clinical practice. Poor ECOG PS, but not advanced age, was associated with shorter OS.

Real-world treatment practice in patients with advanced melanoma in the era before ipilimumab: results from the IMAGE study.

The therapeutic landscape for advanced melanoma has recently been transformed by several novel agents (immune checkpoint inhibitors and molecular-targeted agents). The prospective, multi-site, observational study IMAGE (ipilimumab: management of advanced melanoma in real practice) included a retrospective cohort to describe real-world treatment prior to approval of the immune checkpoint inhibitor ipilimumab. This retrospective cohort of patients, who started second-line/subsequent treatment (index therapy) for advanced melanoma within 3 years before ipilimumab approval, was selected randomly by chart review. Collected data included treatment history, patient outcomes, and healthcare resource utilization. All patients had ≥1 year of follow-up data. This analysis included 177 patients from Europe (69%) and North America (31%). The most common index therapies (used alone or in combination) were fotemustine (23%), dacarbazine (21%), temozolomide (14%), and platinum-based chemotherapy (14%). Most patients (89%) discontinued index treatment during the study period; the most common reason was disease progression (59%). Among patients with tumor assessment (153/177; 86%), 2% had complete response, 5% had partial response, and 12% had stable disease on last tumor assessment. At 1-year study follow-up, median progression-free survival was 2.6 months (95% confidence interval [CI], 2.1-2.9) and median overall survival was 8.8 months (95% CI, 6.5-9.7). During follow-up, 95% of the patients had healthcare visits for advanced melanoma, 74% of whom were hospitalized or admitted to a hospice facility. These results provide insights into patient care with advanced melanoma in the era before ipilimumab and may serve as a benchmark for new agents in future real-world studies.

Retrospective analysis of drug utilization, health care resource use, and costs associated with IFN therapy for adjuvant treatment of malignant melanoma.

BACKGROUND: This study examines real-world drug utilization patterns, health care resource use, and costs among patients receiving adjuvant treatment with IFN versus patients receiving no treatment ("observation") for malignant melanoma following surgery. METHODS: A retrospective cohort study was conducted using administrative claims from Truven Health Analytics (MarketScan(®)) to identify all adjuvant melanoma patients (aged ≥18 years) diagnosed between June 2007 and June 2011 who had a lymph node dissection (ie, index surgery) and were treated with IFN or subsequently observed. Health care resource use and costs of services were converted to 2012 US dollars and were evaluated and compared using multivariable regression. RESULTS: Of 1,999 eligible subjects with melanoma surgery claims, 179 (9.0%) were treated with IFN and 1,820 (91.0%) were observed. The median duration (days) and number of doses of IFN therapy were 73 and 36, respectively. Among IFN-treated patients, only 10.6% completed ≥80% of maintenance therapy. The total average cost for patients treated with IFN was US$60,755±$3,972 (n=179); significantly higher than for patients undergoing observation ($31,641±$2,471; P<0.0001). Similar trends were observed when evaluating total cost components, including melanoma-related and non-melanoma-related medical costs. Among the melanoma-related medical costs, outpatient services, including office visits and laboratory testing, represented between 33% and 53% of total costs and demonstrated the largest difference between IFN-treated and observation patients. Outpatient service costs for IFN-treated patients were $32,414±$2,498, over three times greater than those for observation patients ($10,556±$1,128; P<0.0001). CONCLUSION: The majority of adjuvant melanoma patients in this study was treated with observation versus IFN treatment. Among those who attempted IFN treatment, most could not complete the recommended course of therapy. Health care costs were significantly greater for patients treated with IFN, with the greatest differences being for melanoma-related medical cost components. These findings illustrate the significant economic burden borne by adjuvant melanoma patients and their health insurers.

Incidence and impact of pain conditions and comorbid illnesses.

BACKGROUND: Individuals with pain often present with more than one painful condition. The purpose of this study was to characterize the rates of comorbidity, pain medication use, and health care costs for 23 selected pain conditions in a large health plan using administrative claims data from 2005 to 2007. METHODS: Eligible patients included 1,211,483 adults with at least one pain condition during the one-year study period. Pain condition cohorts were classified based on the first diagnosis present in the claims during the study period. RESULTS: Musculoskeletal pain conditions were among the most prevalent cohorts including low back pain, osteoarthritis, and fibromyalgia. Cancer pain was the least prevalent cohort. Conditions with the lowest illness severity included migraine and painful bladder syndrome cohorts, while cohorts with diabetic neuropathy, human immunodeficiency virus (HIV)-associated pain, and cancer pain were the most severe. Across cohorts, the mean number of comorbid pain conditions ranged from 1.39 (for cancer pain and migraine) to 2.65 (for multiple sclerosis pain). High rates of mental health conditions were found in cohorts with HIV-associated pain and multiple sclerosis pain (42.59% and 34.78%) and were lowest among cohorts with rheumatoid arthritis and psoriatic arthropathy (12.73% and 13.31%), respectively. Rates of sleep disorders ranged from 5.47% (for painful bladder syndrome) to 11.59% (for multiple sclerosis pain). Overall, patients averaged 3.53 unique pain medications during the study period. Considerable annual total health care costs were observed in the cancer pain cohort and the lowest costs were observed in the postherpetic neuropathy, surgically-induced pain, migraine, and irritable bowel syndrome cohorts. Costs attributed to pain were highest among the multiple sclerosis, HIV, and cancer pain cohorts. The highest pharmaceutical costs were observed in the HIV cohort. CONCLUSION: These findings underscore the heterogeneity of patients with pain in terms of burden of illness, costs to the health care system, and the complexity of commonly co-occurring disorders.

A meta-analysis of pain response in the treatment of fibromyalgia.

OBJECTIVE: This meta-analysis compared efficacy (pain response) of drugs that are licensed or commonly used in the treatment of fibromyalgia. A meta-analysis of safety measured via discontinuation because of adverse events was also performed. METHODS: We conducted a meta-analysis of 21 clinical trials to estimate treatment differences vs. placebo, separately, for duloxetine, fluoxetine, gabapentin, milnacipran, pramipexole, pregabalin, either of two tricyclic antidepressants, and tramadol plus paracetamol. Indirect treatment comparisons using mixed treatment comparisons methodology were conducted for all pairwise comparisons. Pain response was analyzed as improvement of at least 30%, and separately of 50%, from baseline. RESULTS: When compared with placebo, statistically significant pain responses (improvement of 30% and 50%) were observed for patients treated with duloxetine, milnacipran 200 mg/day, pregabalin 300 or 450 mg/day, and tramadol plus paracetamol. Treatment with fluoxetine, gabapentin, or milnacipran 100 mg/day resulted in significant findings for the 30% improvement in pain response. The meta-analysis showed a statistically increased risk of discontinuation because of adverse events for milnacipran 100 and 200 mg/day (both P < 0.001), and pregabalin 300 and 450 mg/day (P = 0.009 and P < 0.001, respectively). All other treatments, except fluoxetine, showed numerically increased risk over placebo for discontinuation because of adverse events. In the indirect comparisons, no pairwise comparison of active treatments reached statistical significance for either pain response end point. CONCLUSION: All eight active treatments displayed evidence suggesting improvement over placebo in the treatment of pain in patients suffering from fibromyalgia. Indirect comparison of active treatments found no strong differences.

The epidemiology, economic burden, and pharmacological treatment of chronic low back pain in France, Germany, Italy, Spain and the UK: a literature-based review.

OBJECTIVE: This study's objective was to review the literature on the epidemiological and economic burden and treatment of chronic low back pain (CLBP) in France, Germany, Italy, Spain and the UK. METHODS: A literature search was conducted for 1997 - 2007, focusing on CLBP burden and treatment in the countries of interest. RESULTS: The literature search yielded 1552 articles; 23 sources were included in this review. General population prevalence estimates for CLBP were available for two countries: 5.91% (Italy) and 6.3 - 11.1% (UK). Resource utilization estimates were available for Germany, Italy, Spain and the UK. Patients visited general practitioners and osteopaths. Annual direct costs of low back pain were available only for Germany: > euro 7000 per person. Work absenteeism accounted for 75% of the total per-patient cost of low back pain in Germany. The five identified treatment guidelines recommended a multimodal approach. Recommended pharmacotherapies included NSAIDs, muscle relaxants, analgesics and anesthetics, and opioids. CONCLUSIONS: Prevalence estimates varied, possibly owing to differences in diagnostic criteria and populations studied. Little is known about CLBP's economic burden. Treatment guidelines recommended multimodal treatment.

Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain.

BACKGROUND: Few direct head-to-head comparisons have been conducted between drugs for the treatment of diabetic peripheral neuropathic pain (DPNP). Approved or recommended drugs in this indication include duloxetine (DLX), pregabalin (PGB), gabapentin (GBP) and amitriptyline (AMT). We conducted an indirect meta-analysis to compare the efficacy and tolerability of DLX with PGB and GBP in DPNP, using placebo as a common comparator. METHODS: We searched PubMed, EMBASE, CENTRAL databases and regulatory websites for randomized, double-blind, placebo-controlled, parallel group or crossover clinical trials (RCTs) assessing DLX, PGB, GBP and AMT in DPNP. Study arms using approved dosages with assessments after 5-13 weeks were eligible. Efficacy criteria were: reduction in 24-hour pain severity (24 h PS) for all three drugs, and response rate (>or= 50% pain reduction) and Patient Global Impression of Improvement/Change (PGI-I/C) for DLX and PGB only. Tolerability criteria included: discontinuation, diarrhoea, dizziness, headache, nausea and somnolence. Direct comparisons versus placebo were conducted with pooled fixed - and random-effects analyses on endpoints reported in at least two studies of each drug. Indirect comparisons were performed between DLX and each of PGB and GBP using Bayesian simulation. RESULTS: Three studies of DLX, six of PGB, two of GBP and none of AMT met the inclusion criteria. In random-effects and fixed-effects analyses of DLX, PGB and GBP, all were superior to placebo for all efficacy parameters, with some tolerability trade-offs. Indirect comparison of DLX with PGB found no differences in 24 h PS, but significant differences in PGI-I/C, favouring PGB, and in dizziness, favouring DLX were apparent. Comparing DLX and GBP, there were no statistically significant differences. CONCLUSION: From the few available studies suitable for indirect comparison, DLX shows comparable efficacy and tolerability to GBP and PGB in DPNP. Duloxetine provides an important treatment option for this disabling condition.