Real-world Characteristics and Outcomes of Patients With Metastatic Castration-resistant Prostate Cancer Receiving Chemotherapy Versus Androgen Receptor-targeted Therapy After Failure of First-line Androgen Receptor-targeted Therapy in the Community Setting

Background

In metastatic castration-resistant prostate cancer (mCRPC), optimal treatment sequences are unknown. We assessed second-line taxane (TT) versus androgen receptor-targeted therapy (ART), after initial ART failure, in United States oncology community practices.

Quality of Life and Pain During Treatment of Metastatic Castration-resistant Prostate Cancer With Cabazitaxel In Routine Clinical Practice

BackgroundThis prospective study collected quality of life (QoL) and pain data during cabazitaxel treatment in patients with advanced metastatic or castration-resistant prostate cancer (mCRPC).Patients and MethodsFunctional Assessment of Cancer Therapy-Prostate (QoL) and Brief Pain Inventory-Short Form (pain) questionnaires were collected over 6 months.ResultsIn 61 patients with mCRPC (median age, 72 years) from 22 centers, metastatic sites were bones (97%), lymph nodes (36%), and visceral (20%); 25% received cabazitaxel in the second line, 29% in the third line, and 46% in the fourth line or beyond. All had been previously treated with docetaxel, except one with paclitaxel, and 75% also with abiraterone, enzalutamide, or both. The median cabazitaxel duration was 3.4 months. Forty-nine patients were evaluable for QoL and 44 for pain. QoL was improved in 37%, maintained in 35%, and deteriorated in 37%. In 27%, pain decreased ≥ 1 level and remained stable in 52%. A total of 34% lowered analgesic drug level. Prostate-specific antigen response ≥ 50% was observed in 11 (32.6%) patients, of whom 7 improved QoL and 1 was stable. At 6 months, 83.6% survived (95% confidence interval, 71.7%-90.8%). A total of 46% had ≥ 1 grade ≥ 3 adverse events, mainly anemia and neutropenia.ConclusionAlthough cabazitaxel was given as the third line and beyond for three-quarters of patients, over one-third had improved QoL and/or decreased pain during treatment.     

Real-world Treatment Patterns and Clinical Outcomes Across Lines of Therapy in Patients With Advanced/Metastatic Gastric or Gastroesophageal Junction Cancer

BackgroundFirst-line (1L) and second-line (2L) therapies for advanced/metastatic gastric cancer (GC) and gastroesophageal junction cancer (GEJC) have modest efficacy, and therapeutic options in subsequent lines are limited as disease progresses. We assessed real-world treatment patterns and outcomes for advanced/metastatic GC/GEJC.Patients and MethodsAdult patients diagnosed with advanced/metastatic GC/GEJC between January 1, 2011 and April 30, 2018 were identified using the Flatiron Health database. Median overall survival (OS) from start of each line of therapy until death was estimated by the Kaplan-Meier method. Duration of therapy (DoT) was time from start date until end date of each line.ResultsWe identified 3291 patients with advanced/metastatic GC/GEJC adenocarcinoma. At diagnosis, the median age was 68 years, 60% were white, 53% had initial stage IV disease, and 57% had GC. Of these 3291 patients, most (75%) received at least 1 therapy; 32% received 2L, 14% received third-line (3L) therapy, and 6% received at least 4 lines of therapy (4L+). The median OS from start of 1L was 10.7 months (2L, 7.6 months; 3L, 6.1 months; 4L+, 2.8 months). The median DoT in 1L was 2.2 months (2L, 2.1 months; 3L, 1.7 months; 4L+, 3.0 months). Use of targeted and immunotherapies generally increased progressively with each subsequent line of therapy.ConclusionOne-quarter of patients with advanced/metastatic GC/GEJC remained untreated, and only approximately one-half of patients receiving 1L therapy received subsequent treatment. In all lines of therapy, OS was generally poor and DoT was short. More effective treatment options are needed across all lines of therapy for this highly burdensome disease.     

Androgens and Overall Survival in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Docetaxel

BackgroundPre-treatment androgen levels are associated with overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC) treated with androgen synthesis inhibitors. The current study sought to determine whether pre-treatment serum androgens predict clinical outcome among patients with metastatic CRPC treated with docetaxel chemotherapy.Materials and MethodsData were obtained from 1050 men who were chemotherapy-naive prior to treatment with docetaxel, prednisone, and either bevacizumab or placebo (CALGB 90401). Pretreatment serum assays for testosterone, androstenedione, and dehydroepiandrosterone (DHEA) were performed with tandem liquid chromatography-mass spectrometry.ResultsMedian values for testosterone, androstenedione, and DHEA were 1.00, 13.50, and 8.12 ng/dL, respectively. The median was used to define the midpoint between low and high values. In univariate analysis, median OS for low versus high levels was 21.4 and 24.2 months for testosterone, 23.8 and 21.9 months for androstenedione, and 20.2 and 25.2 months for DHEA (P = NS). In multivariable analysis of all androgens, baseline DHEA was prognostic of ≥ 50% PSA decline from baseline (P = .008). In multivariable analysis adjusting for 10 known prognostic values and prior ketoconazole use for metastatic CRPC, a 10-unit increase in baseline testosterone increased risk of death (hazard ratio, 1.11; 95% confidence interval, 1.01-1.23; P = .039), whereas a 10-unit increase in androstenedione lowered risk of death (hazard ratio, 0.92; 95% confidence interval, 0.88-0.97; P = .001).ConclusionConsistent with prior studies, higher androstenedione levels in patients with metastatic CRPC treated with docetaxel are associated with improved survival. However pretreatment levels of other androgen levels are associated with varied effects on clinical outcome in chemotherapy-treated patients.     

Treatment Patterns and Clinical and Economic Outcomes in Patients With Newly Diagnosed Multiple Myeloma Treated With Lenalidomide- and/or Bortezomib-containing Regimens Without Stem Cell Transplant in a Real-world Setting

BackgroundReal-world data in patients with newly diagnosed multiple myeloma (NDMM) are sparse. Using United States claims databases, we analyzed treatment patterns, clinical outcomes, and health care utilization and costs in patients receiving lenalidomide- and/or bortezomib-containing therapy.Materials and MethodsPatient claims were obtained from a large commercial and Medicare database (October 2009 to May 2015). Patients with NDMM who received lenalidomide- and/or bortezomib-containing therapy and did not receive stem cell transplant (SCT) were analyzed. Duration of treatment (DOT), time to next treatment (TTNT), and health care utilization and costs were evaluated.ResultsOf 3075 patients, 1767 received doublet therapy (814 lenalidomide-dexamethasone [Rd], 953 bortezomib-dexamethasone [Vd]) and 464 received triplet therapy (318 lenalidomide-bortezomib-dexamethasone [RVd], 146 cyclophosphamide-bortezomib-dexamethasone [CyBord]). Rd versus Vd resulted in longer median DOT (12.0 vs. 5.9 months; P < .0001) and median TTNT (36.7 vs. 24.4 months; P = .0005). Year 1 costs were greater with Rd versus Vd (Δ = $14,964; P = .0009), primarily owing to higher pharmacy costs; outpatient physician visits and chemotherapy administration costs were lower. Median DOT (14.8 vs. 9.0 months; P < .0001) and median TTNT (35.7 vs. 22.3 months; P = .0007) were longer with RVd versus CyBord; year 1 costs were comparable.ConclusionsIn this study of patients with NDMM ineligible for transplant, the median duration of therapy was approximately 70% of that in clinical trial observations. Lenalidomide therapy versus Vd and CyBord resulted in longer DOT, which correlated with longer TTNT, and higher pharmacy costs, which were partially offset by lower outpatient and chemotherapy administration costs.     

Comparison of Alternative Androgen Receptor-axis-targeted Agent (ARATA) and Docetaxel as Second-line Therapy for Patients With Metastatic Castration-resistant Prostate Cancer With Progression After Initial ARATA in Real-world Clinical Practice in Japan

Background

The objective of the present study was to assess the oncologic outcomes of patients receiving second-line therapy against metastatic castration-resistant prostate cancer (mCRPC).

Real World Outcomes in Patients With Metastatic,Castration-Resistant Prostate Cancer Treated With Radium-223 in Routine Clinical Practice in Sweden

AimEstimate the effect of Radium-223 (Ra-223) on the incidence of bone fractures, prostate cancer death, and all-cause death compared with other standard treatments for metastatic, castration-resistant prostate cancer (mCRPC).MethodsUsing a cohort design, we estimated the effect of Ra-223 on the risk of bone fractures, all-cause and prostate cancer–specific mortality across different lines of treatment for mCRPC using Prostate Cancer data Base Sweden (2013-2018). The comparator group comprised other standard treatments for mCRPC. We used 36-month risk differences and hazard ratios (HRs) as effect estimates.ResultsThe number of eligible individuals was 635, 453, 262, and 84 for the first-, second-, third-, and fourth-line cohorts, respectively. When compared Ra-223 to other standard treatments, the difference in the 36-month risk of fracture was 6% (95% confidence interval [CI], ?7% to 18%) in the first-line cohort (n = 635) and 8% (95% CI, ?7% to 18%) in the second-line cohort (n = 453). The number of fractures in the third-/fourth-line cohorts was too small for an adjusted comparison. The difference in 36-month mortality was higher in the first-line cohort 13% (95% CI, ?3% to 31%), but lower in the second- and third-/fourth-line cohorts?8% (95% CI, ?23% to 7%) and ?14% (95% CI, ?21% to 16%) respectively. Most deaths were due to prostate cancer.ConclusionResults suggest that the difference in the risk of fractures is small, if any. A difference in the risk of mortality may be present in first-line treatment, but a decreased risk of mortality was observed in second and later lines of treatment. The results on mortality need to be considered in the context of potential unmeasured or residual confounding.     

Safety and Feasibility of Radiation Therapy to the Primary Tumor in Patients With Metastatic Castration-resistant Prostate Cancer

IntroductionThe objective of this study was to evaluate the safety and feasibility of radiation therapy (RT) to the primary tumor in patients with metastatic castration-resistant prostate cancer (mCRPC).Patients and MethodsThis retrospective study included 105 patients with mCRPC who were treated between April 2004 and May 2019. We divided the patients into 2 groups: patients treated with RT to the primary tumor after they developed CRPC (RT group) and without (non-RT group). The primary purpose was safety assessed using the Common Terminology Criteria for Adverse Events. The secondary purpose included prostate-specific antigen (PSA) response, cancer-specific survival (CSS), and overall survival (OS). Background-adjusted multivariate analyses, with the inverse probability of treatment weighting (IPTW) method, were performed to evaluate impact of RT on CSS and OS.ResultsThe median age at CRPC diagnosis was 75 years, and the median follow-up period after CRPC diagnosis was 21 months. The adverse events rates related to RT in any grade and grade ≥ 3 were 55% and 23%, respectively. Nine (29%) patients achieved ≥ 30% PSA decline with RT. In multivariate analyses with the IPTW method, the CSS and OS in the RT group were significantly longer than those in the non-RT group. In subgroup analyses with the IPTW method, RT was significantly associated with improved OS in patients aged ≥ 75 years and patients with initial PSA ≥ 500 ng/mL, cT4, Gleason score ≥ 8, and high-volume metastatic burden.ConclusionsRT to the primary tumor is safe and feasible, and it has potential benefits on oncologic outcomes in patients with mCRPC.     

Abiraterone Followed by Enzalutamide Versus Enzalutamide Followed by Abiraterone in Chemotherapy-naive Patients With Metastatic Castration-resistant Prostate Cancer

Background

Abiraterone (AA) and enzalutamide (ENZA) are increasingly being used in chemotherapy-naive patients with metastatic castration-resistant prostate cancer owing to efficacy and favorable toxicity. However, the order in which they should be administered has not been determined.

Treatment Patterns and Outcomes in Early-stage Hodgkin Lymphoma in the Elderly: A National Cancer Database Analysis

BackgroundThe outcome for early-stage (I/II) Hodgkin lymphoma (HL) has improved significantly during the past few decades. However, older age (≥ 60 years) has continued to be associated with poor outcomes, and a paucity of data is available defining the optimal treatment regimens. In the present study, we sought to identify the practice patterns and outcomes in elderly patients with early-stage HL using the National Cancer Database.Materials and MethodsWe performed a retrospective study of patients aged 60 years with early-stage classic HL diagnosed from 2004 to 2012. The overall survival (OS) of patients undergoing chemotherapy (CT), radiation therapy (RT), or CT plus RT were compared. Kaplan-Meier curves of OS for individual therapy were constructed and compared using the log-rank test. Multivariate analysis for predictors of mortality was conducted using the Cox proportional hazard method.ResultsA total of 3795 patients were included in the analysis. At baseline, 41% patients had stage I disease. Of the 3795 patients, 51% underwent CT, 16% underwent RT, and 33% underwent CT plus RT. With a median follow-up duration of 40.4 months, the unadjusted OS rates for patients receiving CT, RT, or CT plus RT were 58.1%, 54%, and 77.7%, respectively (P < .0001). On multivariate analysis, CT plus RT improved OS compared with monotherapy.ConclusionIn older patients (age ≥ 60 years) with stage I/II HL, the combination of CT plus consolidative RT resulted in improved OS compared with monotherapy. However, the use of combination therapy in this age group seems suboptimal. This could be, in part, secondary to comorbidities limiting the use of CT plus RT in the elderly.     

Evaluation of Response to Enzalutamide Consecutively After Abiraterone Acetate/Prednisone Failure in Patients With Metastatic Castration-resistant Prostate Cancer

Introduction

Treatment of metastatic castration-resistant prostate cancer (mCRPC) has evolved significantly during the past decade, and the preferred combination and/or sequence of these treatments remains controversial. In this retrospective study, we explored clinical and pathologic factors that could predict response to consecutive treatment with enzalutamide (ENZA) after disease progression (PD) on abiraterone acetate and prednisone (AA/P).

Clinical Outcomes of Patients with Metastatic Cancer Receiving Immune Checkpoint Inhibitors in the Inpatient Setting

BackgroundAs indications for immune checkpoint inhibitor (ICI) therapy have increased in recent years, so has the proportion of patients eligible for this type of therapy. However, a lack of data exists about the risks and benefits of ICI therapy in hospitalized patients, who tend to be frailer and sicker than patients enrolled in clinical trials.Material and MethodsWe conducted a retrospective cohort study among hospitalized patients with metastatic solid tumors who received ICI therapy at a large academic cancer center over the course of 4 years. We analyzed the characteristics and outcomes of these patients and identified demographic and clinical factors that could be used to predict mortality.ResultsDuring the 4‐year study period, 106 patients were treated with ICI therapy while admitted to the hospital; 70 (66%) had Eastern Cooperative Oncology Group Performance Status ≥2, which would have prevented them from enrolling in most clinical trials of ICIs. Fifty‐two patients (49%) died either during admission or within 30 days of discharge; median overall survival was 1.0 month from discharge, and 16 patients (15%) were alive 6 months after discharge. Independent predictors of death following receipt of inpatient ICI included a diagnosis of non‐small cell lung cancer relative to melanoma and prior treatment with two or more lines of therapy.ConclusionThe poor overall outcomes observed in this study may give clinicians pause when considering ICI therapy for hospitalized patients, particularly those with characteristics that are associated with a greater risk of mortality.Implications for PracticeImmunotherapy strategies for patients with cancer are rapidly evolving and their use is expanding, but not all patients will develop a response, and secondary toxicity can be significant and challenging. This is especially evident in hospitalized patients, where the economic cost derived from inpatient immune checkpoint inhibitor (ICI) administration is important and the clinical benefit is sometimes unclear. The poor overall outcomes evidenced in the ICI inpatient population in this study highlight the need to better identify the patients that will respond to these therapies, which will also help to decrease the financial burden imposed by these highly priced therapies.     

Relationship Between Metastasis-free Survival and Overall Survival in Patients With Nonmetastatic Castration-resistant Prostate Cancer

BackgroundMetastasis-free survival (MFS) has been shown to be predictive of overall survival (OS) in hormone-sensitive localized prostate cancer. We evaluated the relationship between MFS and OS in nonmetastatic castration-resistant prostate cancer (nmCRPC).Patients and MethodsA retrospective analysis of 1207 high-risk patients with nmCRPC from the SPARTAN study (clinicaltrials.gov, NCT01946204) was undertaken. Landmark analyses of MFS status at several time points from randomization were performed to minimize guarantee-time bias. Hazard ratio (HR) of death as a function of MFS status was estimated based on a Cox proportional hazards model with 2-sided 95% confidence interval (CI). Estimated HRs were adjusted for stratification factors. Correlation analysis was performed using the Fleischer method.ResultsAt all time points, MFS status strongly predicted OS. At landmark time points of 6, 9, and 12 months, risk of death was significantly higher for patients with metastases versus those without (adjusted HR at 6 months = 4.12; 95% CI, 2.60-6.54; P < .0001). MFS was positively correlated with OS based on the Fleischer method (HR, 0.69; 95% CI, 0.69-0.70; P < .0001). Approximately one-half of the variability in OS can be explained by MFS.ConclusionMetastasis development, regardless of time point, is associated with significantly greater risk of death in men with high-risk nmCRPC; hence, MFS is predictive of OS.     

Treatment Patterns and Blood Counts in Patients With Polycythemia Vera Treated With Hydroxyurea in the United States: An Analysis From the REVEAL Study

BackgroundPolycythemia vera (PV) is associated with increased blood cell counts, risk of thrombosis, and symptoms including fatigue and pruritus. National guidelines support the use of hydroxyurea (HU) in high-risk patients or those with some other clinical indication for cytoreduction.Patients and MethodsREVEAL is a prospective, observational study designed to collect data pertaining to demographics, disease burden, clinical management, patient-reported outcomes, and health care resource utilization of patients with PV in the United States. In this analysis, HU treatment patterns and outcomes were assessed from 6 months prior to enrollment to the time of discontinuation, death, or data cutoff.ResultsOf the 1381 patients who received HU for ≥ 3 months, the median HU exposure was 23.6 months (range, 3.1-38.5 months). The most common maximum daily HU doses were 1000 mg (30.6%) and 500 mg (30.1%); only 6.4% received ≥ 2 g/d HU. Approximately one-third (32.3%) of patients had dose adjustments, 23.8% had dose interruptions, and 257 (18.6%) discontinued HU. The most common reasons for HU discontinuations and interruptions were adverse events/intolerance (37.1% and 54.5%, respectively) and lack of efficacy (35.5% and 22.1%, respectively). Of those who received HU for ≥ 3 months, 57.1% had hematocrit values > 45% on ≥ 1 occasion, 33.1% continued to receive phlebotomies, and 27.4% had uncontrolled myeloproliferation.ConclusionThe results of this analysis emphasize the need for active management of patients with PV with appropriate HU dose titration to maintain blood count control while monitoring for signs and symptoms of HU intolerance.     

Utilization Patterns and Trends in Epidermal Growth Factor Receptor (EGFR) Mutation Testing Among Patients With Newly Diagnosed Metastatic Lung Cancer

Introduction

Epidermal growth factor receptor (EGFR)-targeted therapy significantly improves outcomes among patients with non–small-cell lung cancer (NSCLC) whose tumors harbor sensitizing mutations. Patterns of EGFR testing have not been well-documented. The objective of this population-based study is to assess the testing pattern on a national scale.

Real-World Biomarker Testing Patterns in Patients With Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) in a US Community-Based Oncology Practice Setting

Introduction/BackgroundThis study was designed to describe real-world changes in biomarker testing among patients with non-squamous, metastatic non-small cell lung cancer (mNSCLC) in a community oncology setting from 2015 to 2020.Patients and MethodsThis retrospective study randomly selected 500 adult patients diagnosed with nonsquamous mNSCLC to undergo chart review and data extraction. Data were extracted and validated by 2 independent abstractors. Biomarker testing rates were described before and after national guideline updates and FDA approval of targeted agents.ResultsAt least 1 biomarker test was received by 89.4% of patients with mNSCLC. Of all patients, 46.6%, 34.6%, and 8.2% received both single-gene and next generation sequencing (NGS)-based testing, single-gene testing only, and NGS-based testing only, respectively. However, there were changes in testing rates at the time of drug approvals for targeted agents. Biomarker testing increased for ALK (45.0% before to 78.3% after ALK-targeted drug approval), BRAF (from 20.0% to 67.8%), EGFR (from 20.0% to 78.2%), NTRK (from 34.6% to 55.7%), and ROS1 (increased from 29.6% before approval to 74.2% after). Biomarker testing increased after changes were made to national guidelines for BRAF (from 18.8% before to 68.1% after inclusion in guidelines), NTRK (from 37.2% to 56.5%), and ROS1 (increased from 40.8% to 74.5% after guideline updates). Targeted therapy was received by 62.4% of patients with a positive biomarker.ConclusionIncreases in biomarker testing rates were observed relative to targeted agent approvals and national guideline updates. However, many patients with non-squamous mNSCLC did not receive full genotyping in accordance with national guidelines and represent an opportunity to identify reasons and solutions for barriers to care.