Emerging racial disparities among Medicare beneficiaries and Veterans with metastatic castration-sensitive prostate cancer.

BACKGROUND: Previous studies have shown that Black men receive worse prostate cancer care than White men. This has not been explored in metastatic castration-sensitive prostate cancer (mCSPC) in the current treatment era. METHODS: We evaluated treatment intensification (TI) and overall survival (OS) in Medicare (2015-2018) and Veterans Health Administration (VHA; 2015-2019) patients with mCSPC, classifying first-line mCSPC treatment as androgen deprivation therapy (ADT) + novel hormonal therapy; ADT + docetaxel; ADT + first-generation nonsteroidal antiandrogen; or ADT alone. RESULTS: We analyzed 2226 Black and 16,071 White Medicare, and 1020 Black and 2364 White VHA patients. TI was significantly lower for Black vs White Medicare patients overall (adjusted odds ratio [OR] 0.68; 95% confidence interval [CI] 0.58-0.81) and without Medicaid (adjusted OR 0.70; 95% CI 0.57-0.87). Medicaid patients had less TI irrespective of race. OS was worse for Black vs White Medicare patients overall (adjusted hazard ratio [HR] 1.20; 95% CI 1.09-1.31) and without Medicaid (adjusted HR 1.13; 95% CI 1.01-1.27). OS was worse in Medicaid vs without Medicaid, with no significant OS difference between races. TI was significantly lower for Black vs White VHA patients (adjusted OR 0.75; 95% CI 0.61-0.92), with no significant OS difference between races. CONCLUSIONS: Guideline-recommended TI was low for all patients with mCSPC, with less TI in Black patients in both Medicare and the VHA. Black race was associated with worse OS in Medicare but not the VHA. Medicaid patients had less TI and worse OS than those without Medicaid, suggesting poverty and race are associated with care and outcomes.

Budget impact of oral nirmatrelvir/ritonavir in adults at high risk for progression to severe COVID-19 in the United States.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) is indicated for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19. NMV/r has also been authorized for emergency use by the US Food and Drug Administration for the treatment of mild-to-moderate COVID-19 in pediatric patients (aged 226512 years and weighing at least 40 kg) who are at high risk for progression to severe COVID-19. Understanding the budget impact of introducing NMV/r for the treatment of adults with COVID-19 is of key interest to US payers. OBJECTIVE: To estimate the annual budget impact of introducing NMV/r in a US commercial health plan setting in the current Omicron COVID-19 era. METHODS: A budget impact model was developed to assess the impact of NMV/r on health care costs in a hypothetical 1-million-member commercial health insurance plan over a 1-year period in the US population; clinical and cost inputs were derived from published literature with a focus on studies in the recent COVID-19 era that included vaccinated population and predominance of the Omicron variant. In the base-case analysis, it was assumed the only effect of NMV/r was a reduction in incidence (not severity) of hospitalization or death; its potential effect on post-COVID conditions was assessed in a scenario analysis. Outcomes included the number of hospitalizations, total cost, per patient per year (PPPY) costs, and per member per month (PMPM) costs. Sensitivity and scenario analyses were conducted to assess uncertainty around key model inputs. RESULTS: An estimated 29,999 adults were eligible and sought treatment with oral antiviral for COVID-19 over 1 year. The availability of NMV/r was estimated to reduce the number of hospitalizations by 647 with a total budget impact of $2,733,745, $91 PPPY, and $0.23 PMPM. NMV/r was cost saving when including post-COVID conditions with a -$1,510,780 total budget impact, a PPPY cost of -$50, and a PMPM cost of -$0.13. Sensitivity analyses indicated results were most sensitive to the risk of hospitalization under supportive care, risk of hospitalization with NMV/r treatment and cost of NMV/r. CONCLUSIONS: Treatment with NMV/r in the current COVID-19 era is estimated to result in substantial cost offsets because of reductions in hospitalization and modest budget impact to potential overall cost savings.

Plain language summary: Does the amount of time it takes for prostate-specific antigen to double affect how long men with nonmetastatic castration-resistant prostate cancer live and their healthcare costs?

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a research article originally published in Clinical Genitourinary Cancer. The original article described the effect of rapidly rising prostate-specific antigen (PSA) levels on how long men with a type of advanced prostate cancer live and their healthcare costs. The prostate is a part of the male body that helps make semen. PSA is a protein produced by the prostate that can show how advanced prostate cancer has become. One measure of prostate cancer growth is assessing how quickly a patient's PSA level doubles. This is known as the PSA doubling time (PSADT). People with a shorter PSADT usually have faster-growing prostate cancer compared with people who have a longer PSADT of more than 12 months (long PSADT). Researchers wanted to know if PSADT can predict cancer spread (known as metastasis) or death for people with a type of advanced prostate cancer called non-metastatic castration-resistant prostate cancer (nmCRPC). Researchers also wanted to know if PSADT can predict healthcare costs. This could help doctors choose the right treatment for their patients with nmCRPC. This was a real-world study, not a clinical trial. This means that researchers looked at what happened when men received the treatments prescribed by their own doctor as part of their usual healthcare treatment. In this study, researchers used insurance claim information. WHAT WERE THE RESULTS?: Researchers looked at information for 2800 men with nmCRPC. Six out of every 10 men (60%) had a long PSADT of more than 12 months. Researchers found that it took longer for the cancer to spread to other parts of the body in men with a longer PSADT than men with PSADT of 12 months or less. Researchers also found that men with a longer PSADT lived longer than men with PSADT of 12 months or less. The long PSADT group had fewer healthcare visits overall than men with PSADT of 10 months or less. Over time, it cost less to treat men with a long PSADT than men with PSADT of 10 months or less. Generally, if PSADT was shorter, patients tended to do worse. WHAT DO THE RESULTS OF THE STUDY MEAN?: In this real-world study, researchers found that men with nmCRPC lived longer and had lower healthcare costs if they had a long PSADT of more than 12 months compared with men who had a shorter PSADT. Men with nmCRPC and a shorter PSADT may benefit from approved treatments that slow cancer spread and help them live longer. However, these treatments may have side effects and cost more than standard treatment. Doctors take all these things into account when choosing treatments for their patients. Most men in this study had a long PSADT of more than 12 months. Standard treatment may be the right choice for them because they are more likely to have better outcomes than men with a shorter PSADT.

Single-arm studies involving patient-reported outcome data in oncology: a literature review on current practice.

Patient-reported outcomes (PROs) are increasingly used in single-arm cancer studies. We reviewed 60 papers published between 2018 and 2021 of single-arm studies of cancer treatment with PRO data for current practice on design, analysis, reporting, and interpretation. We further examined the studies' handling of potential bias and how they informed decision making. Most studies (58; 97%) analysed PROs without stating a predefined research hypothesis. 13 (22%) of the 60 studies used a PRO as a primary or co-primary endpoint. Definitions of PRO objectives, study population, endpoints, and missing data strategies varied widely. 23 studies (38%) compared the PRO data with external information, most often by using a clinically important difference value; one study used a historical control group. Appropriateness of methods to handle missing data and intercurrent events (including death) were seldom discussed. Most studies (51; 85%) concluded that PRO results supported treatment. Conducting and reporting of PROs in cancer single-arm studies need standards and a critical discussion of statistical methods and possible biases. These findings will guide the Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Data in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) in developing recommendations for the use of PRO-measures in single-arm studies.

Survival and Economic Impact of Rapid Prostate-Specific Antigen Doubling Time in Patients With Nonmetastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: In patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), prostate-specific antigen doubling time (PSADT) is associated with risk of metastasis and survival. This study evaluated the association of PSADT with clinical and economic outcomes in a real-world setting among patients with nmCRPC not receiving novel hormonal therapy (NHT), using 2-month PSADT thresholds. PATIENTS AND METHODS: We retrospectively identified Veterans Health Administration patients with nonmetastatic prostate cancer and ≥2 PSA increases after medical/surgical castration (2012-2016). The third measurement was the index (CRPC) date. Patients with ≥3 postindex PSA measurements, including index, were followed until death or ≥12 months until disenrollment, study end, or death, and grouped into 2-month cohorts based on postindex PSADT. Cox regression models assessed association between PSADT, time to metastasis, and death. Healthcare resource utilization and costs were evaluated. RESULTS: Among 2800 evaluable patients, median follow-up was 30 months and median PSADT was 17 months. Relative to the reference cohort (PSADT >12 months), all cohorts had significantly higher metastasis risk. PSADT ≤10-month cohorts had significantly greater mortality risk than the reference; hazard ratios (95% confidence intervals) ranged from 12.3 (9.2, 16.4) in the PSADT ≤2-month cohort to 1.3 (0.9, 2.0) in the >10 to ≤12-month cohort. Total costs were significantly higher for cohorts up to and including the PSADT >8 to ≤10-month cohort, than for the reference cohort. Mean per patient per month all-cause medical plus pharmacy costs were $6623, $4768, and $4049 in the PSADT ≤2-month, >2 to ≤4-month cohort, and >4 to ≤6-month cohorts, respectively, versus $1911 in the PSADT >12-month cohort (P <0.05). CONCLUSION: Most patients with nmCRPC have PSADT >12 months and a long natural history. For those with shorter PSADT, the risk of metastasis, death, and costs increased. These data can help select patients for NHT and conversely those who can safely delay NHT for nmCRPC.

The Role of Physician Specialty in the Underutilization of Standard-of-Care Treatment Intensification in Patients With Metastatic Castration-sensitive Prostate Cancer.

PURPOSE: We evaluate utilization of treatment intensification of androgen deprivation therapy with androgen receptor pathway inhibitor/docetaxel for metastatic castration-sensitive prostate cancer patients across physician specialties. MATERIALS AND METHODS: This retrospective study identified patients with metastatic castration-sensitive prostate cancer in the Optum Research Database between 2014 and 2019. Adult men with ≥1 claim for metastatic disease within 90 days before or any time after the first prostate cancer claim who received androgen deprivation therapy were included. Physician specialty, determined from medical/pharmacy claims during each line of therapy, was categorized as urologist only, oncologist only, both (urologists and oncologists), or other (other specialties). Treatment intensification and patient characteristics were analyzed descriptively. RESULTS: Of 4,675 patients, 16% were treated by urologists only, 20% by oncologists only, 63% by both, and 1.1% by others. The most frequent first line of therapy was androgen deprivation therapy ± first-generation nonsteroidal antiandrogens (>50%). Androgen deprivation therapy + docetaxel use declined over time, while androgen deprivation therapy + androgen receptor pathway inhibitor use increased. Patients seen by oncologists or both were younger, had fewer comorbidities, and were likelier to receive treatment intensification compared to those treated by urologists. By 2019, however, treatment intensification remained <40% from oncologists only or both, and <15% from urologists only. In the second and third lines of therapy, androgen deprivation therapy + androgen receptor pathway inhibitor was the most prescribed regimen across specialties (>50%). CONCLUSIONS: Treatment intensification was underused in first lines of therapy across urology and oncology specialties despite evidence of improved survival. In subsequent lines, androgen deprivation therapy + androgen receptor pathway inhibitor was prescribed more frequently across specialties. These results underscore the need for earlier treatment intensification by urologists and oncologists.

The cost impact of disease progression to metastatic castration-sensitive prostate cancer.

BACKGROUND: Metastatic prostate cancer (PC) is associated with declining survival rates and increased health care expenditure. However, there are few studies quantifying these increased costs. OBJECTIVE: To estimate overall health care resource utilization and costs associated with progression to metastatic disease in Medicare or commercially insured patients with nonmetastatic castration-sensitive PC (nmCSPC) or previously undiagnosed PC. METHODS: In this retrospective, observational cohort study, we used data from the IBM MarketScan Commercial and MarketScan Medicare Supplemental Databases. Included patients were aged 18 years or older, had 2 or more health care claims associated with a diagnosis of PC, and had a diagnosis of metastatic disease (index date) between January 1, 2014, and December 31, 2016. Patients with PC were identified at index as either progressing from a localized disease state (nmCSPC) without evidence of castration resistance (progressors) or de novo metastatic without a prior PC diagnosis. Unadjusted all-cause direct health care costs for the 2-year pre-index period and up to 2 years post-index were summarized. Metastasis-related incremental all-cause direct health care costs were estimated using regression modeling to adjust for patient baseline characteristics, follow-up duration, and possible selection bias. RESULTS: We identified 3,854 patients who met the criteria for CSPC at metastasis: 2,766 Medicare patients (mean age 78.8 ± 7.6 years) and 1,088 commercial patients (mean age 57.6 ± 4.3 years), with de novo patients accounting for 28.9% and 34.5% of the 2 analysis populations, respectively. Mean unadjusted total all-cause health care costs over the 24-month pre-index period among progressors were $52,661 (Medicare) and $43,111 (commercial); those among de novo patients were $39,756 (Medicare) and $22,090 (commercial). Mean unadjusted post-index costs for progressors were $100,331 (Medicare) and $127,374 (commercial) over a mean follow-up duration of 14.63 and 18.41 months, respectively, and $124,538 (Medicare) and $173,408 (commercial) over a mean follow-up duration of 14.14 and 17.29 months for patients with de novo disease. After multivariate adjustment, incremental cost increases due to metastasis in patients with CSPC pre-index were estimated at $104,051 (Medicare) and $93,334 (commercial), assuming data are available for 24 months post-index. Allowing for variation in the postindex observation period, estimates were $71,308 (Medicare) and $82,336 (commercial). Among de novo patients, cost increases due to metastasis were estimated at $180,932 (Medicare) and $215,397 (commercial), assuming all patients have data for 24 months postindex. Allowing for variable follow-up, estimates were $113,253 (Medicare) and $161,714 (commercial). CONCLUSIONS: Development of metastatic CSPC is associated with considerable costs over a 24-month follow-up period. Cost increases are greater for de novo patients than for those who progressed from localized disease. DISCLOSURES: Q.-D. Trinh received personal fees from Astellas, Bayer, and Janssen and grants from Intuitive Surgical. L. Passos Chaves, Q. Feng, J. Zhu, and T. Abbott are employees of Astellas Pharma Global Development, Inc. R. Sandin is an employee of, and holds stock in, Pfizer AB. This study was funded by Astellas Pharma Inc. (Northbrook, IL) and Pfizer Inc., the codevelopers of enzalutamide. Astellas Pharma Inc. was involved in the study design, data collection, analysis, interpretation of data, and decision to present these results.

Treatment patterns and survival in metastatic castration-sensitive prostate cancer in the US Veterans Health Administration.

BACKGROUND: Limited real-world data exist on treatment patterns and outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: A retrospective cohort study was conducted, using the Veterans Health Administration claims database (April 2013-March 2018). Among 369,734 prostate cancer patients, we selected all men who developed metastases within 90 days before or after medical/surgical castration and who received androgen deprivation therapy (ADT). Patients were categorized into four cohorts: ADT-only (± <90-day nonsteroidal anti-androgen [NSAA] use), ADT + NSAA, ADT + docetaxel, and ADT + abiraterone. Main outcomes were treatment patterns, time-to-progression to metastatic castration-resistant disease, and overall survival. Multivariable analysis and sensitivity analysis were conducted. RESULTS: Of 1395 patients, 874 (63%) received ADT-only, 338 (24%) received ADT + NSAA, 108 (8%) received ADT + docetaxel, and 75 (5%) received ADT + abiraterone. Proportions on ADT-only and ADT + NSAA declined (from 66% to 60% and from 31% to 17%, respectively) over the study period, while proportions prescribed ADT + docetaxel or abiraterone increased from 3% to 9% and from 1% to 15%, respectively. Patients treated with ADT + NSAA had similar risks of castration-resistant disease (hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.87, 1.26) and overall mortality (HR 1.22; 95% CI: 0.97, 1.54) as ADT-only. CONCLUSIONS: Most patients with mCSPC initiating ADT received ADT-only or ADT + NSAA, despite the emergence of docetaxel and novel hormonal therapies. Even in the most recent period (2017 to early 2018), only 24% of men received intensified therapy with agents known to prolong survival versus ADT-only. These data in real-world clinical practice suggest substantial room for improved outcomes in patients with mCSPC.

Survival outcomes in patients with chemotherapy-naive metastatic castration-resistant prostate cancer treated with enzalutamide or abiraterone acetate.

OBJECTIVE: Evaluation of the comparative effectiveness of enzalutamide and abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) is limited to meta-analyses of randomized trials that exclude patients with significant comorbidities. We evaluated overall survival (OS) in patients with chemotherapy-naive mCRPC treated with enzalutamide or abiraterone acetate (abiraterone) in a real-world single payer setting. METHODS: A retrospective analysis (4/1/2014-3/31/2018) of the Veterans Health Administration (VHA) database was conducted. Patients with mCRPC had ≥1 pharmacy claim for enzalutamide or abiraterone (first claim date = index date) following disease progression on surgical/medical castration, without chemotherapy <12 months prior to index date. Patients had continuous VHA enrollment for ≥12 months pre-index date and were followed until death, disenrollment, or end of study. Kaplan-Meier analysis and multivariable Cox proportional hazards regression models examined the OS treatment effect. RESULTS: Patients with chemotherapy-naive mCRPC (N = 3174; enzalutamide, n = 1229; abiraterone, n = 1945) had mean ages of 74 and 73 years, respectively. Median follow-up was 18.27 and 19.07 months with enzalutamide and abiraterone, respectively. Enzalutamide-treated patients had longer median treatment duration than abiraterone-treated patients (9.93 vs 8.47 months, respectively, p = 0.0008). After baseline comorbidity adjustment, enzalutamide-treated patients had a 16% reduced risk of death (hazard ratio [HR] = 0.84; 95% CI, 0.76-0.94; p = 0.0012). For patients who remained on first line-therapy only, enzalutamide-treated patients had improved OS versus abiraterone-treated patients (HR = 0.71; 95% CI, 0.62-0.82). Enzalutamide-treated patients who crossed over to abiraterone had a comparable risk of death versus abiraterone-treated patients who crossed over to enzalutamide (HR = 1.10; 95% CI, 0.89-1.35). These results were confirmed by sensitivity analysis, which considered prognostic variables. CONCLUSIONS: Retrospective analysis of the VHA database indicated that chemotherapy-naive patients with mCRPC initiating therapy with enzalutamide had improved survival versus abiraterone.

The patient's perspective on treatment with dacomitinib: patient-reported outcomes from the Phase III trial ARCHER 1050.

Aim: Patient-reported symptoms, functioning and overall quality of life (QoL) were compared between dacomitinib and gefitinib in ARCHER 1050. Patients & methods: Patients (n = 448) with advanced EGFR mutation-positive non-small-cell lung cancer completed the EORTC-QLQ-C30 questionnaire and its lung-specific module, LC-13. Mean scores over time were analyzed using a mixed model for repeated measures. Results: Both treatments showed early improvement in disease-related symptoms that was maintained during treatment. Treatment-related diarrhea and sore mouth decreased following dose reduction with dacomitinib. There were no clinically meaningful changes in functioning and overall QoL in either treatment group. Conclusion: Longer treatment duration, enabled by dose reduction, allowed patients on dacomitinib to improve treatment-related symptoms and maintain functioning and overall QoL for longer than gefitinib.

Economic Outcomes in Patients with Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide or Abiraterone Acetate Plus Prednisone.

INTRODUCTION: Prostate cancer (PC) is the second leading cause of cancer death among US men and accounts for considerable healthcare expenditures. We evaluated economic outcomes in men with chemotherapy-naïve metastatic castration-resistant PC (mCRPC) treated with enzalutamide or abiraterone acetate plus prednisone (abiraterone). METHODS: We performed a retrospective analysis on 3174 men (18 years or older) utilizing the Veterans Health Administration (VHA) database from 1 April 2014 to 31 March 2018. Men with mCRPC were included if they had at least one pharmacy claim for enzalutamide or abiraterone (first claim date = index date) following surgical or medical castration, had no chemotherapy treatment within 12 months prior to the index date, and had continuous VHA enrollment for at least 12 months pre- and post-index date. Men were followed until death, disenrollment, or end of study and were 1:1 propensity score matched (PSM). All-cause and PC-related resource use and costs per patient per month (PPPM) in the 12 months post index were compared between matched cohorts. RESULTS: We identified 1229 men with mCRPC prescribed enzalutamide and 1945 prescribed abiraterone with mean ages of 74 and 73 years, respectively. After PSM, each cohort had 1160 patients. The enzalutamide cohort had fewer all-cause (2.51 vs 2.86; p < 0.0001) and PC-related outpatient visits (0.86 vs 1.03; p < 0.0001), with corresponding lower all-cause ($2588 vs $3115; p < 0.0001) and PC-related ($1356 vs $1775; p < 0.0001) PPPM outpatient costs compared with the abiraterone cohort. All-cause total costs (medical and pharmacy) PPPM ($8085 vs $9092; p = 0.0002) and PC-related total costs PPPM ($6321 vs $7280; p < 0.0001) were significantly lower in the enzalutamide cohort compared with the abiraterone cohort. CONCLUSIONS: Enzalutamide-treated men with chemotherapy-naïve mCRPC had significantly lower resource utilization and healthcare costs compared with abiraterone-treated men.

Prostate cancer (PC) is the second leading cause of death among men with cancer in the USA. Healthcare costs associated with PC, including hospitalizations, outpatient visits, and medications prescribed to treat adverse effects, depend on the severity of the disease and intensity of treatment, but are generally very high. Enzalutamide and abiraterone acetate with prednisone (abiraterone) are both approved treatments for men with PC that does not respond to treatments that reduce the male hormone testosterone, known as castration-resistant PC (CRPC). These drugs are associated with varying treatment duration and different adverse effects, and therefore could result in differences in the use of healthcare resources and overall cost of treatment. Here we evaluated the healthcare resource utilization (HCRU), which was calculated as the average number of healthcare encounters, including inpatient stays, outpatient visits, and pharmacy visits, and length of inpatient stays, and treatment costs associated with use of enzalutamide or abiraterone by men with metastatic CRPC (mCRPC), who had not received prior chemotherapy in the Veterans Health Administration. We found that men with chemotherapy-naïve mCRPC treated with enzalutamide used less healthcare resources and incurred lower total healthcare costs than men treated with abiraterone. On average, all-cause total healthcare costs were $1007 per patient per month lower and PC-related total healthcare costs were $959 per patient per month lower for patients treated with enzalutamide than those treated with abiraterone. These results support the hypothesis that the long-term HCRU and costs of enzalutamide may be lower compared with abiraterone.

Systematic review and network meta-analysis of first-line therapy for advanced EGFR-positive non-small-cell lung cancer.

Here, we compare the relative clinical efficacy of EGFR-targeted tyrosine kinase inhibitors (EGFR TKIs) for EGFR-positive advanced non-small-cell lung cancer (NSCLC). The authors systematically searched 11 electronic databases from January 2004 to August 2018 for randomized controlled trials measuring clinical efficacy of first-line TKI therapies. Clinical efficacy outcomes included overall survival and progression-free survival. Bayesian network meta-analysis was used to assess the relative efficacy of first-line EGFR TKIs for overall survival and progression-free survival. This network meta-analysis showed that dacomitinib and osimertinib resulted in improved efficacy outcomes compared with afatinib, erlotinib and gefitinib. Both osimertinib and dacomitinib should be considered as standard first-line treatment options for patients diagnosed with advanced EGFR-positive non-small-cell lung cancer.

Management of common adverse events related to first-line dacomitinib use in EGFR mutation-positive non-small-cell lung cancer: a pooled safety analysis.

Aim: This pooled safety analysis was conducted to analyze incidence and management of key dacomitinib-associated adverse drug reactions (ADRs). Patients & methods: Patients with EGFR mutation-positive advanced non-small-cell lung cancer who received first-line dacomitinib at the 45 mg/day recommended starting dose were included. ADRs were identified based on reasonable association with EGFR tyrosine kinase inhibitors. Results: Overall, 251/255 patients (98%) experienced ADRs. The most common were diarrhea, rash, stomatitis, nail disorder and dry skin. Dose interruptions and dose reductions were reported in 47 and 52% of patients, respectively. Fewer grade 3 key ADRs were observed following dose reductions. Conclusion: Dacomitinib was generally tolerable. Most reported ADRs were known to be associated with EGFR tyrosine kinase inhibitors and were managed with standard medical management and dose modifications.

Real-world cost-effectiveness of targeted therapy in metastatic renal cell carcinoma in Sweden: a population-based retrospective analysis.

OBJECTIVE: To explore cost-effectiveness of targeted therapies (TTs) in the treatment of metastatic renal cell carcinoma (mRCC) in a real-world context using a nationwide population-based approach. METHODS: Data on patients diagnosed with mRCC between 2002 and 2012 were extracted from Swedish national health data registers. To facilitate comparisons of patients diagnosed before and after TT introduction to the market, three cohorts were derived: pre-TT introduction (preTT), patients diagnosed 2002-2005; early TT introduction (TTi), patients diagnosed 2006-2008; and late TT introduction (TTii), which was limited to patients diagnosed 2009-2010 to ensure availability of total health care resource utilization (HCRU) data. Patients were followed until end of 2012. The value of TTs across cohorts was estimated using mean HCRU costs per life-year (LY) gained. Data on HCRU were obtained through national health registers for dispensed medication and inpatient and outpatient care, and the associated costs were estimated using the Lin method to account for censoring. LYs gained were defined as the difference in mean survival over the study period. RESULTS: The preTT, TTi, and TTii cohorts consisted of 1,366, 1,158, and 806 patients, respectively. Mean survival in years from mRCC diagnosis was 1.45 in the preTT cohort, 1.62 in the TTi cohort, and 1.83 in the TTii cohort. The respective mean total HCRU cost per patient over the study period was US$16,894, US$29,922, and US$30,037. The cost per LY gained per cohort was US$78,656 for TTi vs preTT, US$34,132 for TTii vs preTT, and US$523 for TTii vs TTi. CONCLUSION: Given common willingness-to-pay per LY gained thresholds, this study in a real-world population suggests the use of TTs in the Swedish mRCC population is increasingly cost-effective over time.

Axitinib, cabozantinib, or everolimus in the treatment of prior sunitinib-treated patients with metastatic renal cell carcinoma: results of matching-adjusted indirect comparison analyses.

BACKGROUND: In the absence of head-to-head trials comparing axitinib with cabozantinib or everolimus, the aim of this study was to conduct an indirect comparison of their relative efficacy in patients with metastatic renal cell carcinoma (mRCC), using data from the AXIS and METEOR trials. METHODS: Progression-free survival (PFS) and overall survival (OS) in prior sunitinib-treated patients with mRCC were compared by conducting matching-adjusted indirect comparison (MAIC) analyses, including base-case and sensitivity analyses. Individual patient-level data from prior sunitinib-treated patients who received axitinib in AXIS were weighted to match published baseline characteristics of prior sunitinib-treated patients who received either cabozantinib or everolimus in METEOR. RESULTS: There was no statistically significant difference in PFS (aHR [adjusted hazard ratio] = 1.15 [CI: 0.82-1.63]) and OS (aHR = 1.00 [CI: 0.69-1.46]) between axitinib versus cabozantinib in the base-case analysis. In the sensitivity analysis, PFS (aHR = 1.39 [CI: 1.00-1.92]) and OS (aHR = 1.35 [CI: 0.95-1.92]) were shorter for axitinib compared with cabozantinib; however, the OS difference was not statistically significant. Axitinib was associated with significantly longer PFS compared with everolimus in the base-case (aHR = 0.53 [CI: 0.36-0.80]) and sensitivity analyses (aHR = 0.63 [CI: 0.45-0.88]), respectively. Results suggested an OS benefit for axitinib versus everolimus in base-case analyses (aHR = 0.63 [CI: 0.42-0.96]); however, the difference in OS in the sensitivity analysis was not statistically significant (aHR = 0.84 [CI: 0.59-1.18]). CONCLUSIONS: MAIC analyses suggest PFS and OS for axitinib and cabozantinib are dependent on the Memorial Sloan Kettering Cancer Center definition used; in the base-case analysis, there was no significant difference in PFS and OS between axitinib and cabozantinib. In the sensitivity analysis, PFS in favour of cabozantinib was significant; however, the trend for prolonged OS with cabozantinib was not significant. For axitinib and everolimus, MAIC analyses indicate patients treated with axitinib may have an improved PFS and OS benefit when compared to everolimus. Disparities between the base-case and sensitivity analyses in this study underscore the importance of adjusting for the differences in baseline characteristics and that naïve indirect comparisons are not appropriate.

Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial.

BACKGROUND: Dacomitinib is a second-generation, irreversible EGFR tyrosine kinase inhibitor. We compared its efficacy and safety with that of the reversible EGFR tyrosine kinase inhibitor gefitinib in the first-line treatment of patients with advanced EGFR-mutation-positive non-small-cell lung cancer (NSCLC). METHODS: In this international, multicentre, randomised, open-label, phase 3 study (ARCHER 1050), we enrolled adults (aged ≥18 years or ≥20 years in Japan and South Korea) with newly diagnosed advanced NSCLC and one EGFR mutation (exon 19 deletion or Leu858Arg) at 71 academic medical centres and university hospitals in seven countries or special administrative regions. We randomly assigned participants (1:1) to receive oral dacomitinib 45 mg/day (in 28-day cycles) or oral gefitinib 250 mg/day (in 28-day cycles) until disease progression or another discontinuation criterion was met. Randomisation, stratified by race and EGFR mutation type, was done with a computer-generated random code assigned by a central interactive web response system. The primary endpoint was progression-free survival assessed by masked independent review in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT01774721, and is ongoing but no longer recruiting patients. FINDINGS: Between May 9, 2013, and March 20, 2015, 452 eligible patients were randomly assigned to receive dacomitinib (n=227) or gefitinib (n=225). Median duration of follow-up for progression-free survival was 22·1 months (95% CI 20·3-23·9). Median progression-free survival according to masked independent review was 14·7 months (95% CI 11·1-16·6) in the dacomitinib group and 9·2 months (9·1-11·0) in the gefitinib group (hazard ratio 0·59, 95% CI 0·47-0·74; p<0·0001). The most common grade 3-4 adverse events were dermatitis acneiform (31 [14%] of 227 patients given dacomitinib vs none of 224 patients given gefitinib), diarrhoea (19 [8%] vs two [1%]), and raised alanine aminotransferase levels (two [1%] vs 19 [8%]). Treatment-related serious adverse events were reported in 21 (9%) patients given dacomitinib and in ten (4%) patients given gefitinib. Two treatment-related deaths occurred in the dacomitinib group (one related to untreated diarrhoea and one to untreated cholelithases/liver disease) and one in the gefitinib group (related to sigmoid colon diverticulitis/rupture complicated by pneumonia). INTERPRETATION: Dacomitinib significantly improved progression-free survival over gefitinib in first-line treatment of patients with EGFR-mutation-positive NSCLC and should be considered as a new treatment option for this population. FUNDING: SFJ Pharmaceuticals Group and Pfizer.

Overall survival in Swedish patients with renal cell carcinoma treated in the period 2002 to 2012: Update of the RENCOMP study with subgroup analysis of the synchronous metastatic and elderly populations.

BACKGROUND: This retrospective study investigated overall survival (OS) and factors influencing OS in Swedish patients with metastatic renal cell carcinoma (mRCC) during the pre- (2002-2005), early (2006-2008), and late (2009-2012) targeted therapy (TT) era. METHODS: Three national Swedish registries identified patients with mRCC. Median OS was estimated using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards regression. Subgroup analysis was conducted for patients with synchronous metastases (M1) and the elderly (aged≥75y). RESULTS: A total of 4,217 patients with mRCC were identified, including 1,533 patients with M1 and 1,275 elderly patients. For patients with mRCC diagnosed in 2002 to 2005, 2006 to 2008, and 2009 to 2012, median OS was 10.0, 13.0, and 18.0 months. Similarly, median OS improved in the M1 and elderly populations. Elderly patients were less likely to be prescribed TT (≥75 vs.<75y): 18.3 vs. 63.5% (in 2006-2008) and 28.6% vs. 55.9% (in 2009-2012). Diagnosis of mRCC in 2009 to 2012, nephrectomy and TT prescription were associated with improved OS in the total mRCC, M1, and elderly populations. CONCLUSION: This real-world study showed continued significant improvement in mRCC OS during the late TT era, including in M1 and elderly populations. TT should be considered for all patients with mRCC based on tolerability, regardless of age.

Overall survival in renal cell carcinoma after introduction of targeted therapies: a Norwegian population-based study.

BACKGROUND: This population-wide retrospective, non-interventional registry study assessed changes in overall survival (OS) and factors influencing OS in Norwegian patients with renal cell carcinoma (RCC). METHODS: Two population-wide health registries were used to identify all RCC patients with (mRCC) or without metastases diagnosed before (2002-2005) and after (2006-2008 and 2009-2011) introduction of targeted therapies. Median OS was estimated using Kaplan-Meier method. Cox proportional hazards regression modeling was used to identify prognostic factors. RESULTS: Overall, 5,463 patients were diagnosed with RCC during 2002-2005 (n=1,898), 2006-2008 (n=1,631), and 2009-2011 (n=1,934); of these, 1,678 (31%) had mRCC. Patients diagnosed in 2009-2011 and 2006-2008 had significant (P<0.001) improvements in OS versus those diagnosed in 2002-2005: median OS, not reached and not reached versus 82.0 months in RCC; 14.0 and 12.0 months versus 9.0 months in mRCC. Similarly, OS improvements were seen in the primary and elderly (≥75 years) mRCC populations. Median OS was comparable (12 months) between clear cell and papillary mRCC, but it was longer (24.0 months) for chromophobe mRCC. Multivariate regression analyses showed that younger age, previous nephrectomy, and 1 or more prescriptions of targeted therapy were significantly associated with longer OS in mRCC patients. CONCLUSION: OS increased in RCC and mRCC patients in Norway between 2002 and 2011 following introduction of targeted therapies.