Ma, Haijun

e19505 Background: CFZ combined with dexamethasone is approved to treat pts with RRMM, with CFZ given once-weekly at 70 mg/m2 (Kd70 QW) or twice-weekly at 56 mg/m2 (Kd56 BIW). No randomized trials have directly compared Kd70 QW with Kd56 BIW. We performed a post hoc comparison between pts who received Kd56 BIW in the ENDEAVOR trial and pts who received Kd70 QW in the A.R.R.O.W. or CHAMPION-1 trials. Methods: Data were analyzed from 3 trials of CFZ in RRMM: A.R.R.O.W. (240 pts in Kd70 QW arm; 2–3 prior therapies and refractory to most recent therapy), CHAMPION-1 (104 pts received Kd70 QW; 1–3 prior therapies), and ENDEAVOR (464 pts in Kd56 BIW arm; 1–3 prior therapies). Pts who received Kd70 QW in A.R.R.O.W. and CHAMPION-1 were pooled and compared with pts who received Kd56 BIW in ENDEAVOR. As study populations slightly varied among the 3 trials, an analysis of safety and efficacy was performed in a subgroup of pts who received 2–3 prior therapy lines and were not refractory to bortezomib (BTZ). Also, we performed regression analyses (controlling for age, ISS stage, BTZ and lenalidomide refractory status, and number of prior regimens) among all pts in the trials who received Kd70 QW or Kd56 BIW. Results: Among BTZ non-refractory pts with 2–3 lines of prior therapy, median progression-free survival (PFS) was 12.1 months (95% CI 8.4–14.3) for Kd70 QW (n = 146) and 14.5 months (95% CI 10.2–NE) for Kd56 BIW (n = 217), and the overall response rate (ORR) was 69.9% (95% CI 61.7–77.2) for Kd70 QW and 72.4% (95% CI 65.9–78.2) for Kd56 BIW. The rate of grade ≥3 adverse events (Kd70 QW vs Kd56 BIW) was 67.6% and 85.3%; among adverse events of interest, the grade ≥3 rate was 1.4% and 5.1% for cardiac failure, 3.4% and 6.0% for renal failure, and 5.5% and 15.7% for hypertension. Kd70 QW represents a convenient and well-tolerated treatment modality for pts with RRMM. In a Cox proportional hazards model, the hazard ratio for PFS (Kd70 QW vs Kd56 BIW) was 0.91 (95% CI 0.69–1.19), and in a logistic regression model the odds ratio for ORR (Kd70 QW vs Kd56 BIW) was 1.12 (95% CI 0.74–1.69). Conclusions: This post hoc analysis suggests that once-weekly Kd70 has a comparable benefit-risk profile to twice-weekly Kd56. Clinical trial information: NCT02412878, NCT01677858, NCT01568866.

Abstract Combination of carfilzomib with dexamethasone (Kd) is approved for use in relapsed and/or refractory multiple myeloma (RRMM), with carfilzomib administered twice weekly at 56 mg/m 2 (Kd56 BIW) or once weekly at 70 mg/m 2 (Kd70 QW). Post hoc cross‐trial comparisons were performed to compare efficacy and safety profiles of Kd70 QW vs Kd56 BIW dosing schedules using data from three trials of patients with RRMM: A.R.R.O.W., CHAMPION‐1, and ENDEAVOR. To select for comparable patient populations, side‐by‐side efficacy and safety comparisons were performed in subgroups of patients with 2‐3 prior lines of therapy who were not refractory to bortezomib. The overall response rate (ORR) was 69.9% (95% confidence interval [CI], 61.7‐77.2) for Kd70 QW and 72.4% (95% CI, 65.9‐78.2) for Kd56 BIW. Median progression‐free survival (PFS) was 12.1 months (95% CI, 8.4‐14.3) for Kd70 QW and 14.5 months (95% CI, 10.2—not evaluable) for Kd56 BIW. Frequency of grade ≥ 3 adverse events (AEs) was 67.6% for Kd70 QW and 85.3% for Kd56 BIW. Regression analyses (adjusting for prognostic factors) of all patients in the trials who received Kd70 QW vs Kd56 BIW estimated a PFS hazard ratio of 0.91 (95% CI, 0.69‐1.19; P = .47) and an ORR odds ratio of 1.12 (95% CI, 0.74‐1.69; P = .61). These results suggest that Kd70 QW has a comparable efficacy profile compared with Kd56 BIW and represents a convenient and well‐tolerated treatment for patients with RRMM.

Abstract BACKGROUND: Most cancer patients with bone metastases report significant pain and substantial impairment in their ability to function. In particular, patients with MM are susceptible to bone pain because of bone damage. Patient-reported outcomes such as a general health outcome measure and a legacy pain instrument may provide valuable information in determining the impact of this condition. The goal of this study was to provide a descriptive profile of health status for cancer patients using the EQ-5D-3L (EQ-5D), a commonly used tool to measure health utility scores. Another goal is to evaluate the predictive information provided by the Brief Pain Inventory (BPI), a self-report pain assessment tool designed to capture pain severity and interference in patients. These information may be useful in estimating the health status of patients where the EQ-5D was not administered. METHODS: Data was pooled across three denosumab registrational trials '20050136', '20050103', and '20050244'. Patients completed the EQ-5D and the BPI at baseline. Eligible patients had histologically confirmed advanced cancers, radiographic evidence of at least one bone metastasis (or lytic bone lesion from multiple myeloma), ECOG of 2 or better and adequate organ function. Using data from patients with MM (N=168), descriptive statistics were used to present summary information on health-related quality of life states and utility scores. Linear regressions were used to examine how BPI severity and interference subscale scores relate with EQ-5D utility scores. Ordinal regressions were used to evaluate how well BPI items predict EQ-5D individual items. Bonferroni adjustments were made when evaluating the relationships of BPI items to individual EQ-5D items. These analyses were repeated using data across several groups of cancer patients to determine if similar results can be obtained (breast cancer, N=2,044, prostate cancer, N=1,819 and others, N=1,509). RESULTS: About 9% of MM patients reported perfect health compared with 11% of all cancer patients. Of the 5 dimensions measured by the EQ-5D, the MM cohort rated pain (80%) the highest with moderate to extreme problems. This was followed by usual activities (68%), mobility (63%), anxiety/depression (49%), and self-care (36%). Similar order was observed across all cancer groups, but with slightly lower percentages for most items: pain (78%), usual activities (58%), mobility (55%), anxiety/depression (57%), and self-care (26%). Although pain interference subscale score explained more of the variability in the EQ-5D utility scores compared with pain severity items in the MM cohort (39% vs 31%) and for all patients (41% vs 34%), model fit was less than ideal (mean squared error=0.23 - 0.25). Hence, BPI items were fitted into individual EQ-5D items. Ordinal regression models fitting BPI items into individual EQ-5D items for the MM cohort showed good predictive power as measured by the concordance index c for mobility (86%), self-care (80%), usual activities (83%), pain (90%) and anxiety/depression (78%). For all patients, similar model fit were obtained for mobility (83%), self-care (78%), usual activities (81%), pain (90%) and anxiety/depression (72%). Further examination of the ordinal regression models across all groups showed that three BPI pain severity items, 'pain at its worst', 'average pain' and 'pain now' in addition to interference with activity and interference with work significantly predicted the EQ-5D pain item. Five interference items, activity, walking ability, work, sleep and enjoyment of life significantly predicted the EQ-5D usual activities item. Finally, 'pain now' and four interference items, relationship with others, enjoyment of life, mood, and activity significantly predicted the EQ-5D anxiety/depression item. CONCLUSIONS: Patients with MM reported several functional limitations on the EQ-5D. Majority of the patients reported moderate to extreme problems in all EQ-5D dimensions except self-care. Model fit of ordinal regression models relating BPI items with EQ-5D items are reasonable underscoring the benefit of using the BPI for planning patient care and health status evaluation. This consistency was also found across cancer groups that primarily include breast and prostate. The resultant model demonstrates the significant contribution of pain severity and interference in determining health status in this patient population. Disclosures Mendoza: Amgen Inc.: Consultancy. Shi:Amgen Inc.: Consultancy. Ma:Amgen Inc.: Employment. Zhang:Amgen Inc.: Employment. Qian:Amgen Inc.: Employment. Cleeland:Amgen Inc.: Consultancy.

Background:Carfilzomib (CFZ) combined with dexamethasone is approved to treat patients (pts) with relapsed and/or refractory multiple myeloma (RRMM), with CFZ given once‐weekly at 70 mg/m2 (Kd70 QW) or twice‐weekly at 56 mg/m2 (Kd56 BIW). No randomized trials have directly compared Kd70 QW with Kd56 BIW.Aims:We performed a post hoc comparison between pts who received Kd56 BIW in the ENDEAVOR trial and pts who received Kd70 QW in the A.R.R.O.W. or CHAMPION‐1 trials.Methods:Data were analyzed from 3 trials of CFZ in RRMM: A.R.R.O.W. (240 pts in Kd70 QW arm; 2–3 prior therapies and refractory to most recent therapy), CHAMPION‐1 (104 pts received Kd70 QW; 1–3 prior therapies), and ENDEAVOR (464 pts in Kd56 BIW arm; 1–3 prior therapies). Pts who received Kd70 QW in A.R.R.O.W. and CHAMPION‐1 were pooled and compared with pts who received Kd56 BIW in ENDEAVOR. As study populations slightly varied among the 3 trials, an analysis of safety and efficacy was performed in a subgroup of pts who received 2–3 prior therapy lines and were not refractory to bortezomib (BTZ). Also, we performed regression analyses (controlling for age, ISS stage, BTZ and lenalidomide refractory status, and number of prior regimens) among all pts in the trials who received Kd70 QW or Kd56 BIW.Results:Among BTZ non‐refractory pts with 2–3 lines of prior therapy, median progression‐free survival (PFS) was 12.1 months (95% CI 8.4–14.3) for Kd70 QW (n = 146) and 14.5 months (95% CI 10.2–NE) for Kd56 BIW (n = 217), and the overall response rate (ORR) was 69.9% (95% CI 61.7–77.2) for Kd70 QW and 72.4% (95% CI 65.9–78.2) for Kd56 BIW. The rate of grade ≥3 adverse events (Kd70 QW vs Kd56 BIW) was 67.6% and 85.3%; among adverse events of interest, the grade ≥3 rate was 1.4% and 5.1% for cardiac failure, 3.4% and 6.0% for renal failure, and 5.5% and 15.7% for hypertension. Kd70 QW represents a convenient and well‐tolerated treatment modality for pts with RRMM. In a Cox proportional hazards model, the hazard ratio for PFS (Kd70 QW vs Kd56 BIW) was 0.91 (95% CI 0.69–1.19), and in a logistic regression model the odds ratio for ORR (Kd70 QW vs Kd56 BIW) was 1.12 (95% CI 0.74–1.69).Summary/Conclusion:This post hoc analysis suggests that once‐weekly Kd70 has a comparable benefit‐risk profile to twice‐weekly Kd56.© 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.

AbstractBackgroundWe aimed to provide a simple, descriptive health‐status profile for cancer patients with bone metastases, based on the EuroQol EQ‐5D, a tool commonly used to measure health utility scores, and to evaluate its association with the Brief Pain Inventory (BPI), a legacy pain‐assessment tool. Although pain is one of five health‐status dimensions measured by the EQ‐5D, our understanding of how pain relates to the other EQ‐5D dimensions is limited.MethodsWe derived data from 5500 patients with bone metastases who completed the EQ‐5D and BPI. Regression analyses examined how BPI severity and interference scores correlated with EQ‐5D utility scores and how BPI items associated with EQ‐5D items, for the entire sample and by disease‐type subgroup.ResultsRegardless of cancer site, the percentage of patients reporting moderate/severe problems in each of the five EQ‐5D dimensions were pain/discomfort, 78%; usual activities, 58%; mobility, 55%; anxiety/depression, 57%; and self‐care, 26%. BPI pain interference explained more of the variability in the EQ‐5D utility scores than did pain severity (R2 = 41% vs. 34%). BPI worst pain, average pain, pain now, interference with general activity, and interference with work significantly predicted EQ‐5D pain/discomfort, with odds ratio estimates <1.ConclusionsPain/discomfort was the worst‐rated dimension of the EQ‐5D in this population, but the relationship of this item to BPI pain severity was modest, suggesting that the single pain item of the EQ‐5D may be of limited utility in studies for which pain is an endpoint.SignificanceHealth‐status dimensions include more than pain. We examine the contribution of pain severity and pain‐related functional interference in determining the health status of cancer patients with bone metastases. The pain dimension from a health‐status measure may be an inadequate metric in clinical trials/clinical practice when pain is an important outcome.

Abstract Effective assessment and management of pain in patients with cancer is strengthened by the patient's report of how much pain interferes with daily functioning. This requires a clear delineation of different levels of pain interference. We derived optimal cutpoints for differentiating between mild, moderate, and severe pain interference assessed by the Brief Pain Inventory (BPI) and describe the prevalence and characteristics of pain-induced functional impairment in patients with cancer. Data were pooled across 3 Phase III pivotal trials. Patient-completed questionnaires included the EuroQol 5 dimensions questionnaire (EQ5D), Functional Assessment of Cancer Therapy–General Measure (FACT-G), and BPI. Optimal cutpoints for categorizing pain interference into 3 levels were derived using analysis of variance, with different cutpoint sets for BPI total interference (BPI-PITS, the average score of all 7 items), activity-related interference (BPI-WAW, the average score of work, general activity, and walking), and mood-related interference (BPI-REM, the average score of relations with others, enjoyment of life, and mood) as independent variables and EQ5D–visual analog scale and total FACT-G score as dependent variables. To validate the cutpoints, we assessed whether interference categories were in concordance with Eastern Cooperative Oncology Group performance status (ECOG-PS) levels. The optimal cutpoints were (2,5) for BPI-PITS, (2,6) for BPI-WAW, and (2,5) for BPI-REM. The mild (<2), moderate (2-5 or 2-6), and severe (>5 or >6) pain interference groups were significantly concordant with ECOG-PS levels (P < 0.0001). We empirically derived patient-reported pain interference categories in relation to clinician-rated performance status. These cutpoints may facilitate the conduct and interpretation of clinical evaluation, symptom epidemiology, and clinical trials.