Jackson Tang

Background: Metastatic castration-resistant prostate cancer (mCRPC) treatment commonly includes first-line (1L) androgen receptor pathway inhibitors (ARPIs) followed by second-line (2L) taxane-based chemotherapy. Adverse events (AEs) may lead to early taxane discontinuation, which can negatively affect outcomes and costs. This retrospective observational study assessed real-world outcomes, AEs, and costs of 2L taxane therapy by number of cycles among patients with mCRPC previously treated with a 1L ARPI; outcomes were compared with patients receiving 2L ARPI. Methods: Overall survival (OS; overall and by number of taxane cycles received) was determined for 2L taxane and compared with 2L ARPI using the Flatiron Health electronic health record database (Jul 1, 2012, to Jun 30, 2020). Taxane-related AEs and associated costs were estimated using the IQVIA PharMetrics® Plus claims database (Jan 1, 2013, to Aug 31, 2021). Results: Overall, 2L ARPI ( n = 473) vs. taxane ( n = 214) was associated with longer median OS (15.4 vs. 13.6 months). Patients receiving > 8 ( n = 48) vs. ≤ 8 taxane cycles ( n = 166) had longer median OS (18.4 vs. 11.9 months; p = 0.006). Patients receiving > 8 vs. ≤ 8 taxane cycles were also more likely to experience an AE (95% vs. 88%) but had lower mean AE-related total healthcare costs per patient per month ($3,429 vs. $6,334). Conclusion: Patients who received > 8 cycles of 2L taxane had longer observed survival. However, these results are subject to selection bias and immortal time bias. Prospective or time-adjusted analyses are needed.

Introduction: Novel triplet regimens containing immunomodulatory drugs and proteasome inhibitors (PIs) have improved outcomes and extended survival for patients (pts) with RRMM. However, use of combination therapies (tx) over an extended period may increase tx-related symptom burden and impact health-related quality of life (HRQoL). In the randomized phase 2 ELOQUENT-3 trial (NCT02654132), the efficacy and safety of elotuzumab (ELO) + pomalidomide + dexamethasone (EPd) vs pomalidomide + dexamethasone (Pd) were assessed in pts with RRMM previously treated with lenalidomide (LEN) and a PI. EPd had a 46% reduction in the risk of death vs Pd, without increasing toxicity or affecting HRQoL through 18.3 months (mo) follow-up (f/u) (Dimopoulos MA, et al. N Engl J Med 2018;379:1811-1822; Weisel K, et al. Blood 2019;134[suppl 1];Abstract 3480). To inform tx decision-making, it is important to measure how effective tx can preserve HRQoL without a negative impact. Here we evaluate updated HRQoL findings from ELOQUENT-3 after 4 years of EPd tx (data cutoff, February 2021), including the first report of responder analyses. Methods: Pt-reported outcomes (PROs) were exploratory endpoints, assessed using the EuroQoL 5 dimension 3 level (EQ-5D-3L) instrument and the MD Anderson Symptom Inventory MM module (MDASI-MM). EQ-5D-3L incorporates a global health visual analog scale (VAS; score range 0-100) and a descriptive system consisting of 5 dimensions to which UK empirically derived weights were applied to generate a utility index (UI; score range −0.59 to −1); MDASI-MM measures total symptom severity (20 items) and symptom interference (6 items) (score range 0-10). Minimally important differences (MIDs)/responder definitions were 0.08 (UI), 7 (VAS), or based on the standard error of the mean (MDASI-MM). Higher scores indicate better health for EQ-5D-3L, but more severe symptoms for MDASI-MM. PRO data were collected at baseline (BL), the start of every 28-day tx cycle, the end of tx, and during f/u every 3 mo. All randomized pts with BL and ≥ 1 post-BL assessment were included in the PRO analysis. Completion rates are presented out of the expected population. Changes from BL were evaluated descriptively and using a mixed model for repeated measures. Time to first deterioration was defined as time to first change from BL that was at least the responder definition threshold; hazard ratios (HR) were calculated using a Cox proportional hazard model. Responder analyses present the proportion of improved/stable/worsened pts at each time point based on responder definition. Results: Of 117 randomized pts, 106 (EPd n=55; Pd n=51) were included in PRO analyses. BL characteristics of the PRO population were balanced between arms and representative of the entire study population. Except for 2 cycles, PRO completion rates were ≥ 80% for both PROs for all on-tx time points where ≥ 10 pts remained on study. Although 11 pts remained on EPd until cycle 29, between-tx arm HRQoL analysis was not feasible after cycle 13 due to low Pd pt numbers. After end of tx, f/u PRO data were available for a longer period for EPd vs Pd (for ≥ 10 pts up to f/u visit 6 (18 mo) for EPd and up to f/u visit 2 (6 mo) for Pd). Mean BL scores were similar between EPd and Pd arms, and least squares mean change from BL data showed no overall clinically meaningful differences between tx arms for EQ-5D-3L UI or VAS, or MDASI-MM total symptom severity, symptom interference, or items of pain, fatigue, or bone pain. For the EPd tx arm, the proportion of pts who either improved or maintained stable HRQoL based on responder analyses up until cycle 13 ranged 82%-96% for MDASI total symptom score and 64%-85% for MDASI symptom interference (Fig. 1). There were no statistically significant differences in time to first deterioration between arms for key EQ-5D-3L and MDASI-MM scales. Kaplan-Meier plots presenting f/u data up to 48 mo were overlapping, indicating no HRQoL differences between EPd and Pd (Fig. 2). Conclusions: HRQoL was similar between pts who received triplet EPd and doublet Pd in ELOQUENT-3, thus the addition of ELO to Pd did not significantly impact time to deterioration in HRQoL over an extended f/u period. These pt-reported findings complement existing f/u data showing that EPd tx resulted in clinically meaningful improvements in survival without detriment to HRQoL, further supporting the clinical value of EPd in adult pts with RRMM who have received ≥ 2 prior tx including LEN and a PI.

E21011 Background: First line (1L) systemic combination (combo) therapies for treatment of metastatic melanoma (MM) include targeted combo therapies such as dabrafenib+trametinib (D+T) or vemurafenib+cobimetinib for patients (pts) with BRAF mutation (BRAF+), or immunotherapy combo ipilimumab+nivolumab (I+N) for pts irrespective of BRAF status. The objective of this study was to describe real world characteristics and treatment patterns among BRAF+ mm pts who were treated with either D+T or I+N as 1L therapy. Methods: This retrospective observational study utilized Flatiron Health’s electronic health record (EHR) data from Jan 2013 to Jul 2016. Pts were aged ≥18 years with a mm diagnosis, and treated with either D+T (N = 86) or I+N (N = 61) as 1L therapy. Prior to therapy initiation, 86/86 of D+T pts were tested BRAF+. 55/61 of I+N pts completed BRAF testing and 19/61 were BRAF+. All analyses focused on BRAF+ pts who were treated with either D+T or I+N as 1L therapy. Baseline characteristics, treatment patterns and data on therapy discontinuation were collected from structured data in patient records and unstructured data in physician notes, and were descriptively assessed. Statistical inferences were not drawn due to sample size limitations. Results: At baseline, 35% of D+T pts vs 32% of I+N pts had brain metastasis, 29% of D+T pts vs 11% of I+N pts had high LDH levels, and 20% of D+T pts vs 42% of I+N pts reported ECOG = 0 status. The median follow-up time was 219 days for the D+T pts vs 150 days for the I+N pts. The 3 and 6 month discontinuation rates were 9% and 24% for the D+T pts vs 21% and 47% for the I+N pts. 13% of D+T pts vs 26% of I+N pts discontinued treatment citing toxicity in physician notes. Among pts with brain metastasis, the 3 and 6 month discontinuation rates were 3% and 20% for D+T pts vs 33% and 50% for I+N pts. Conclusions: Among BRAF+ mm pts who were treated with either D+T or I+N as 1L therapy, D+T pts were more likely to have advanced disease such as brain metastasis and high LDH levels than I+N pts. Compared with 1L D+T pts, 1L I+N pts had higher discontinuation rates due to toxicity, even with a shorter median follow-up time. 1L I+N pts with brain metastasis also had higher discontinuation rates.

E21003 Background: Guidelines for metastatic melanoma (MM) recommend targeted therapy combination (combo) for patients (pts) with BRAF mutation (BRAF+) and immunotherapy for pts irrespective of BRAF status. The study objective was to describe real world characteristics and treatment patterns among mm pts treated with either dabrafenib+trametinib (D+T) or ipilimumab+nivolumab (I+N) combo therapies. Methods: This retrospective observational study utilized Flatiron Health’s electronic health record (EHR) data. Included pts were ≥18 years and treated with either D+T or I+N (post mm diagnosis) from Jan 2013 - Jul 2016. Baseline characteristics, treatment patterns and data on therapy discontinuation were collected from structured data in patient records and unstructured data in physician notes. Non-parametric statistical tests were used in light of sample size limitations. Results: 135 D+T pts and 75 I+N pts were included. Median age was 60 for D+T pts and 64 for I+N pts. 69% of D+T pts were male vs 68% of I+N pts. Most pts were Caucasian (82% for both). Before receiving combo therapy, 100% of D+T pts vs 31% of I+N pts were BRAF+, 38% of D+T pts vs 31% of I+N pts had brain metastasis (mts) (p > .05), 25% of D+T pts vs 16% of I+N pts had high LDH levels (p = .05), and 18% of D+T pts vs 35% of I+N pts reported ECOG = 0 status (p < .01). Median follow-up time was 234 days for D+T pts vs 173 days for I+N pts (p < .01). 64% of D+T pts vs 81% of I+N pts received combo therapy as first line (1L) therapy (p = .02). The 3 and 6 month discontinuation rates were 9% and 24% for D+T 1L pts; 12% and 26% for I+N 1L pts; and 21% and 47% for the subset of I+N 1L BRAF+ pts. 13% of D+T 1L pts vs 28% of I+N 1L pts discontinued treatment over the follow-up period citing toxicity in physician notes (p = .05). Among pts with brain mts, the 3 and 6 month discontinuation rates were 3% and 20% for D+T 1L pts; 24% and 35% for I+N 1L pts; and 33% and 50% for I+N 1L BRAF+ pts. Conclusions: Prior to initiation of combo therapy, D+T pts had more advanced disease: pts were more likely to have brain mts, high LDH level, receive D+T as 2L+ therapy, and less likely to have ECOG = 0 status than I+N pts. I+N 1L pts were more likely to discontinue therapy due to toxicity than D+T 1L pts even with a shorter median follow-up time.

Background: A retrospective cohort study using GE Centricity electronic medical records assessed the association between post-index hypoglycemia and HbA1c with discontinuation and down-titration of sulfonylureas among patients with Type 2 diabetes mellitus. Methods: Adult patients with an index prescription for a sulfonylurea and ≥12 months’ continuous records pre- and post-index were eligible. Sulfonylurea discontinuation and down-titration was assessed 1-year post-index. Discontinuation occurred if the date of a prescription was >90 days from the preceding prescription plus days of supply. Down-titration occurred when a subsequent prescription was lower than the index dose. Cox regression assessed the association between post-index hypoglycemia and HbA1c with time to sulfonylurea discontinuation and down-titration, as well as other factors. Results: 28,371 participants were included in the study; 13,459 (47.4%) were discontinuers, 717 (2.5%) were down-titraters, and 14,195 (50.0%) were continuers. 0.6% of continuers experienced hypoglycemia 1-year post-index, compared with 3.1% of down-titraters and 0.8% of discontinuers (p < 0.0001). Patients with post-index hypoglycemia had a significantly higher rate of discontinuation (hazard ratio [HR] = 1.82, 95% CI: 1.47–2.23) and down-titration (HR = 4.25, 95% CI: 1.92–8.03). Patients with higher post-index HbA1c and use of 2^nd generation sulfonylureas had an increased rate of discontinuation (HR = 1.05, 95% CI: 1.04–1.06; HR = 1.19, 95% CI: 1.14–1.24, respectively). Conclusion: Approximately half of participants who initiated sulfonylureas discontinued or down-titrated therapy within one year. Both post-index hypoglycemia and higher HbA1c were significant risk factors for sulfonylurea treatment change.

Objectives: Sulfonylurea therapy among patients with type 2 diabetes mellitus (T2DM) can be disrupted due to adverse events, including hypoglycemia. A retrospective study using the MarketScan claims database quantified the frequency of sulfonylurea discontinuation or down-titration and identified associated risk factors. Research design and methods: Adult patients with an index sulfonylurea prescription between 2008 and 2012 and 1 year continuous enrollment pre- and post-index were included. Therapy changes assessed over 1 year post-index included discontinuation and down-titration. Discontinuation occurred if the date of a fill was >90 days from the end date of the preceding fill. Down-titration occurred when a fill had a lower equivalent dose than the fill on the index date. Kaplan–Meier methods estimated the probability of either discontinuation or down-titration over 12 months, and Cox regression models identified associated risk factors. Results: A total of 104,082 sulfonylurea users were included in the study and the probability of either discontinuation or down-titration at 3, 6 and 12 months was 23.2%, 38.9%, and 52.3%, respectively. Major risk factors associated with therapy changes included post-index hypoglycemia (discontinuation hazard ratio [HR] = 1.78 [1.68, 1.89]; down-titration HR =2.79 [2.40, 3.23]) and concomitant use of insulin (discontinuation HR =1.48 [1.40, 1.57]; down-titration HR =1.82 [1.56, 2.11]). Other risk factors included younger age, female gender, use of second generation sulfonylureas, prior cardiovascular comorbidity and liver disease. Limitations: The study was not able to assess unreported, potentially mild cases of hypoglycemia, nor was it able to evaluate the association between changes in therapy and HbA1c levels or body weight. Conclusions: More than half of T2DM patients who initiated sulfonylurea therapy discontinued or down-titrated within 1 year. Insulin use and hypoglycemia were associated with sulfonylurea therapy change.

9560 Background: Current systemic therapies of metastatic melanoma (MM) include immunotherapy, target therapy (if BRAF mutated), high-dose IL-2, and chemotherapy, all of which are associated with different toxicity and adverse events (AEs). A comprehensive understanding of the costs of AEs will enable more accurate comparisons among the treatments and better management of costs. Methods: Two retrospective cohort studies were independently conducted using IMS PharMetrics Plus databases and MarketScan commercial and Medicare supplemental databases. Patients included those aged ≥ 18 years who had ≥ 1 metastatic melanoma diagnosis and ≥ 1 claim for any systemic therapies from July 1, 2004 to June 30, 2015. AEs were identified based on ICD-9-CM diagnosis/procedure codes. Incremental cost per AE was determined by comparing the 30-day expenditures between patients with the AE event and patients without the event using a generalized linear model. Propensity score with inverse probability of treatment weighted method was used to adjust for baseline demographic and clinical differences. Results: 1,654 patients from PharMetrics were included. Mean age was 61.2 years (SD ± 11.4); mean baseline Charlson comorbidity index was 8.0 (SD ± 2.3); 59% were male. 1,329 patients included from MarketScan had similar characteristics. The adjusted 30-day incremental costs by AE category in 2015 US$ are summarized below in the table. Conclusions: Incremental AE costs associated with systemic therapies of mm are substantial.

E21003 Background: The National Comprehensive Cancer Network (NCCN) recommends systemic therapy, including target therapy, immunotherapy, and chemotherapy, for metastatic melanoma (MM). BRAF mutations help inform the choice of therapy. This study aims to to describe the treatment pattern of mm patients before and after BRAF testing in the US. Methods: Two retrospective cohort studies were conducted using MarketScan commercial and Medicare supplemental databases and IMS PharMetrics Plus databases. Patients included those aged ≥ 18 years who had ≥ 1 mm diagnosis and received BRAF testing after mm diagnosis from August 1, 2011 to September 30, 2015. Patients with non-melanoma primary malignancy were excluded. Patients who received BRAF testing were identified based on Current Procedural Terminology (CPT) codes. Systemic therapies before and after BRAF testing were compared. Cost of the test and time from test to systemic therapy were evaluated. Results: 1,577 and 919 mm patients who received BRAF testing were included from MarketScan and Pharmetrics, respectively. Results from MarketScan analysis were as follows: the most recent systemic therapies before test were: no systemic therapy 96.3%; target therapy 0.3%; immunotherapy 2.5%; chemotherapy 1.0%, while the most recent systemic therapies after test were 58.4%, 12.1%, 23.0% and 6.5%, respectively. Median time from diagnosis to test and from test to the therapy was 34 and 47 days, respectively. The mean (±SD) costs of test was $515 (±$1011). Results from PharMetrics were similar. Conclusions: After BRAF testing, mm patients were more likely to receive systemic therapy. Many mm patients remained untreated after BRAF testing.