Quality-of-life (QOL) analyses in patients with multiple myeloma: Results from the selinexor (KPT-330) treatment of refractory myeloma (STORM) phase IIb study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20522-e20522
Author(s):  
Sundar Jagannath ◽  
jyotsna mehta ◽  
Janis Breeze ◽  
Gabriel Tremblay ◽  
Lingling Li ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Nuclear Export ◽  
Multicenter Trial ◽  
Open Label ◽  
Specific Domain ◽  
Level Data ◽  
Patient Reported ◽  
Trial Outcome Index ◽  
Outcome Index ◽  
Definition Of

e20522 Background: Selinexor, a novel oral selective inhibitor of nuclear export, was recently approved for use in relapsed/refractory multiple myeloma (MM). The efficacy and safety of selinexor and dexamethasone was evaluated in a phase 2b, single-arm, open-label, multicenter trial in patients with penta-exposed, triple-class refractory MM. Patient-reported outcomes were measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) assessment. While minimal clinically important differences (MCID) have been established for other FACT scales, there is no known, validated definition of MCID for the FACT-MM. This study reports results of QoL analyses in patients with MM enrolled in the STORM phase 2b trial and examines two approaches to calculate MCID for the FACT-MM. Methods: FACT-MM data were collected at baseline, on day 1 of each 4-week cycle, and at end of treatment (EOT) during the STORM phase 2b trial. Change from baseline was analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain. Two approaches for evaluating MCID were explored: the first based on patient-reported assessment of meaningful change, defined as 10% of the instrument range (Ringash 2007), and the second based on mean baseline differences between ECOG groups (0 vs 1 to 2) based on patient level data. Additional analyses were performed to identify trends among treatment responders and non-responders, including a difference-in-difference (DID) analysis to compare changes between baseline and EOT. Results: Eighty patients had sufficient data to be included in longitudinal QOL analyses. MCID analyses demonstrated that most patients did not experience decline during the first six cycles of treatment; this pattern was consistent with MCID defined either as 10% of the instrument range (range 54% to 75% of patients), or as an ECOG-based anchor (range: 54% to 73% of patients). The DID analysis found that the mean change in QoL of non-responders decreased significantly between baseline and EOT, while responders had no significant change. This difference between responders and non-responders was significant for the FACT-G. Conclusions: Most patients did not experience QoL decline during the early cycles of selinexor treatment during the STORM 2b trial. The MCID decline, evaluated by two approaches, was greater among treatment non-responders than responders. A DID approach demonstrated greater decline between baseline and EOT for non-responders. Clinical trial information: NCT02336815.

Patient-reported outcomes (PROs) from the systemic therapies for HER2-positive metastatic breast cancer (MBC) registry study (SystHERs): Eliciting the patient experience.

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 286-286 ◽  
Author(s):  
Sara A. Hurvitz ◽  
Mohammad Jahanzeb ◽  
Peter Kaufman ◽  
Ginny Mason ◽  
Musa Mayer ◽  
...  
Keyword(s):  
Patient Experience ◽  
Economic Burden ◽  
Metastatic Breast ◽  
Reference Ranges ◽  
Her2 Positive ◽  
Job Effectiveness ◽  
Patient Reported ◽  
Trial Outcome Index ◽  
Observational Cohort ◽  
Outcome Index

286 Background: Patients with HER2-positive MBC are, on average, living longer. Data are limited on patient-reported quality of life (QoL) and economic burden during these extended survival periods. In accordance with guidelines for comparative effectiveness research in oncology (Basch et al, 2012), SystHERs, initiated in 2012, includes PROs to capture the patient experience. Here we report baseline (at enrollment) PRO results from SystHERs. Methods: SystHERs is a US-based prospective observational cohort study that aims to enroll 1000 patients with HER2-positive MBC within 6 months of metastatic diagnosis. Patients will be followed for 5–8 years.PROs, including QoL, economic burden, and symptoms related to neuropathy, alopecia, and cognition, are collected at baseline and ~90-day intervals during clinic visits, including after disease progression. Results: As of Feb 17, 2014, 319 patients were enrolled, and baseline data from 306 eligible patients are reported. Median time to enrollment since MBC diagnosis was 2.4 months. At least 1 PRO item was completed by 90% of eligible patients. Scale reference ranges (higher scores indicate better status) and median scores at baseline were: overall HRQoL (0–100)=80.0; FACT-B Trial Outcome Index (0–96)=58.0, and the Rotterdam Activities of Daily Living Scale (0–100)=85.7. One hundred patients (40.3%) were employed. These patients reported on average 36% work time missed (absenteeism) and 30% decreased on-the-job effectiveness (presenteeism) due to MBC. Patients reported a median out-of-pocket MBC-related expenditure of $735 in the past 3 months (range $0–11,700). Of this, the median deductible and copay-related cost was $350. Conclusions: To our knowledge, this is the only HER2-positive MBC patient registry that includes comprehensive PROs to supplement clinical data. To date, participation in PROs is high at baseline (90%).QoL and economic burden were consistent with other studies (Cortés et al, 2013; Zafar et al, 2013). Baseline results for ~500 patients are expected by the time of the congress presentation and will include data on symptoms related to neuropathy, alopecia, and cognition. Clinical trial information: NCT01615068.

Selinexor containing regimens in patients with multiple myeloma (MM) previously treated with anti-CD38 monoclonal antibodies (αCD38 mAbs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20020-e20020
Author(s):  
Cristina Gasparetto ◽  
Brea Lipe ◽  
Sascha Tuchman ◽  
Nizar J. Bahlis ◽  
Heather J. Sutherland ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Nuclear Export ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Median Number ◽  
Open Label ◽  
Previously Treated ◽  
Functional Inactivation ◽  
Dose Modifications

e20020 Background: Exportin 1 (XPO1) mediates the nuclear export and functional inactivation of tumor suppressor proteins, is required for MM growth, is associated with poor prognosis in MM and mediates resistance to standard MM therapies. Selinexor (SEL) is a first-in-class, oral selective inhibitor of nuclear export (SINE) compound approved in combination with dexamethasone (dex) ± bortezomib for patients (pts) with previously treated MM. Once MM becomes refractory to αCD38 mAb, pts have limited effective treatment options and poor prognosis. Overall response rate (ORR) to the first regimen after refractoriness to an αCD38 mAb is 31%, median progression-free survival (mPFS) is 3.4 months (m), and median overall survival (mOS) is 8.6 m. The doublet SEL-dex (Xd) has shown ORR ̃26% in triple-class (IMID, PI, αCD38 mAb) refractory MM; SEL-based triplets could be more effective in this population. Methods: STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) is a multi-arm, open-label, Phase 1b/2 study evaluating SEL in various triplet combinations. Here, we retrospectively analyzed the efficacy and safety of SEL-containing triplets in pts previously treated with αCD38 mAbs. Pts received SEL-dex (Xd) plus pomalidomide (XPd, n = 19), bortezomib (XVd, n = 4), lenalidomide (XRd, n = 4), daratumumab (XDd, n = 2) or carfilzomib (XKd, n = 18). ORR, mOS, mPFS and adverse events (AEs) were analyzed. Results: Among the 47 pts, median age 64 yrs, female 53%, median time from diagnosis 5.1 yrs, median number of prior regimens 5 (range, 2–11). Prior daratumumab (96%), isatuximab (4%); 96% had MM refractory to aCD38 mAb, 81% had triple-class refractory MM, 74% and 47% were quad- and penta-exposed, 43% and 15% had quad- and penta-refractory MM. αCD38 mAb was included in the immediate prior regimen of 57% of pts and median duration from end of most recent aCD38 mAb therapy to first dose of study treatment was 6.9 weeks (range, 2.6-114.9). ORR was 51% among the 45 evaluable pts, 59% in the XPd arm (n = 17; 2 pts were not efficacy evaluable) and 67% in the XKd arm. ORR was 47% (9/19) among pts with quad-refractory MM and evaluable efficacy. Among all evaluable pts mPFS was 8.8 m (95% CI: 4.9, NE) and mOS was 20.4 m (95% CI: 9.6, NE). Among the 25 pts with αCD38 mAb in their immediate prior regimen, efficacy was similar to that regimen: ORR 52% vs. 45%, mPFS 8.8 vs. 9.3 m. The most common treatment emergent AEs were nausea (72%), anemia (64%), thrombocytopenia (60%), fatigue (57%), which were managed with standard supportive care and dose modifications. Conclusions: SEL-containing triplets in pts with MM previously treated with αCD38 mAbs, most of whom had triple-class refractory MM, exhibit tolerability and comparable effectiveness to their most recent αCD38 mAb-containing regimens. Compared to historical control, mOS was much higher among these patients. Further investigation is warranted. Clinical trial information: NCT02343042.

Health-related quality of life (HRQoL) patient-reported outcomes (PROs) and survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 53-53
Author(s):  
Lorente David ◽  
Rebeca Lozano ◽  
Guillermo de Velasco ◽  
Nuria Romero-Laorden ◽  
Elena Castro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Well Being ◽  
Castration Resistant Prostate Cancer ◽  
Kaplan Meier ◽  
Patient Reported ◽  
Trial Outcome Index ◽  
Related Quality ◽  
Health Related ◽  
Outcome Index

53 Background: HRQoL is a relevant endpoint in trials in advanced prostate cancer. An association between HRQoL and OS has been reported. The Functional Assessment of Cancer Therapy-Prostate (FACT-P) is a validated HRQoL PRO in mCRPC. Methods: We evaluated the association between FACT-P and OS in the COU-301 and COU-302 trials (abiraterone vs placebo in mCRPC pts). FACT-P scores, sub-scores (physical (PWB), emotional (EWB), functional (FWB), social (SWB) well-being, prostate cancer subscale (PCS) FACT-G and the Trial Outcome Index (TOI) were calculated. A decrease in 3 (PWB, EWB, SWB, FWB, PCS), 9 (FACT-G, TOI) or 10 (FACT-Total) points after 3 cycles was considered clinically relevant. The association between FACT-P and OS was evaluated with Kaplan-Meier, Cox-regression models and c-indices. Results: 2,177 pts (COU-301: 1,121 /COU-302: 1,056) had valid baseline (BL) FACT-P scores. Mean BL score was 106.6 (COU-301) and 122.3 (COU-302). BL total scores were associated with OS in both COU-AA-301 (p<0.001) and COU-302 (p<0.001), independent of treatment. All FACT-P sub-scores except SWB were associated with OS (Table). A decrease in FACTP scores was associated with decreased OS in COU-301 (19.6 vs 14.2m; HR: 1.8; p<0.001) and COU-302 (34.4 vs 27.7m; HR: 1.3; p=0.009) datasets. Conclusions: BL FACTP scores (except SWB subscale) are significantly associated with outcome. Early declines in HRQoL can be observed and are associated with worse outcome. Prospective evaluation of the significance of changes in HRQoL is needed. YODA Project 2018-3745.[Table: see text]

scholarly journals Review of patient-reported outcomes in multiple myeloma registrational trials: highlighting areas for improvement

2021 ◽  
Vol 11 (8) ◽  
Author(s):  
Laura L. Fernandes ◽  
Jiaxi Zhou ◽  
Bindu Kanapuru ◽  
Erica Horodniceanu ◽  
Thomas Gwise ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Patient Experience ◽  
Patient Reported Outcomes ◽  
Mixed Model ◽  
Open Label ◽  
Mixed Model Analysis ◽  
Patient Reported ◽  
Trial Protocols ◽  
Eortc Qlq ◽  
Collection Methods

AbstractOver the past 13 years, there have been advances in characterizing the patient experience in oncology trials, primarily using patient-reported outcomes (PROs). This review aims to provide details on the PRO measures and analyses used in multiple myeloma (MM) registrational trials. We identified registrational trials supporting MM indications from 2007 to 2020 from FDA databases. Trial protocols, statistical analysis plans, and clinical study reports were reviewed for PRO measures used, collection methods, statistical analyses, baseline and instrument completion definitions, and thresholds for clinical meaningfulness. Twenty-five trials supporting 20 MM indications were identified; 17 (68%) contained submitted PRO data. Of the 17 trials, 14 were randomized controlled trials and the remainder were single-arm trials. All but one trial were open label trials. Seven trials collected data electronically and five in paper format. The majority of trials evaluated at least two PRO measures (82%) with two trials (12%) utilizing four measures. Nine unique PRO measures were used, most commonly the EORTC QLQ-30 (87%), EQ-5D (65%), and QLQ-MY20 (47%). All 17 (100%) trials provided descriptive summaries, 10 (59%) carried out longitudinal mixed model analysis, 9 (53%) conducted responder analysis, and 2 (12%) did a basic inferential test. We noted substantial heterogeneity in terms of PRO collection methods, measures, definitions, and analyses, which may hinder the ability to effectively capture and interpret patient experience in future MM clinical trials. Further research is needed to determine the most appropriate approaches for statistical and analytical methodologies for PRO data in MM trials.

Phase 2, open-label study of venetoclax in combination with carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS8056-TPS8056
Author(s):  
Orlando Bueno ◽  
Tu Xu ◽  
Jaclyn Cordero ◽  
Lura Morris ◽  
Jeremy Ross ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitor ◽  
Unmet Need ◽  
Predictive Biomarkers ◽  
The United States ◽  
Phase 2 ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Patient Reported

TPS8056 Background: A significant unmet need for multiple myeloma (MM) therapy remains as many patients eventually relapse after or become refractory to current treatment options. Investigation of novel agents and combinations in relapsed/refractory (R/R) patients are therefore critical to advance therapy and improve patient outcomes. Venetoclax is a potent, selective, orally bioavailable inhibitor of BCL-2. Combination of venetoclax with dexamethasone and bortezomib, a proteasome inhibitor that can inhibit MCL-1 indirectly via stabilizing the MCL-1-neutralizing protein NOXA, showed high rates of clinical response in a Phase 1 study. The mechanism of MCL-1 inhibition is thought to be a class effect of proteasome inhibitors. Given the clinical data supporting the combination of venetoclax with a proteasome inhibitor, this study will evaluate whether venetoclax combined with carfilzomib and dexamethasone can provide a well-tolerated and efficacious treatment option for R/R MM patients. Methods: This Phase 2, open-label study will assess the combination of venetoclax, carfilzomib, and dexamethasone in patients with R/R MM (NCT02899052). Primary objectives are to assess the safety and tolerability of this combination. Secondary objectives include evaluation of the pharmacokinetics of venetoclax and carfilzomib, preliminary efficacy of the combination (including overall response rate, very good partial response or better rate, progression-free survival, time to progression, and duration of response), and minimal residual disease (MRD) in bone marrow by next generation sequencing. Exploratory objectives will assess pharmacodynamic and predictive biomarkers, MRD by PET, pharmacogenetics, and patient-reported outcomes. Safety and pharmacokinetic profiles of the combination will be evaluated in initial dose escalation cohorts to determine appropriate doses of venetoclax and carfilzomib to be used with dexamethasone; a dose expansion phase will evaluate the safety and efficacy profiles of the combination based on selected doses. Study recruitment began in January 2017, with target enrollment of ~40 patients from 10–15 sites in the United States. Clinical trial information: NCT02899052.

scholarly journals Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology–RTOG 1203

2018 ◽  
Vol 36 (24) ◽  
pp. 2538-2544 ◽  
Author(s):  
Ann H. Klopp ◽  
Anamaria R. Yeung ◽  
Snehal Deshmukh ◽  
Karen M. Gil ◽  
Lari Wenzel ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Radiation Therapy ◽  
Intensity Modulated Radiation Therapy ◽  
Intensity Modulated ◽  
Patient Reported ◽  
Trial Outcome Index ◽  
Gi Toxicity ◽  
The Mean ◽  
Outcome Index

Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index. Results From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group ( P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group ( P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group ( P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea ( P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04). Conclusion Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patient’s perspective.

A phase III, randomized, multicenter, open-label study of venetoclax or pomalidomide in combination with dexamethasone in patients with t(11;14)-positive relapsed/refractory multiple myeloma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS8554-TPS8554
Author(s):  
Maria-Victoria Mateos ◽  
Philippe Moreau ◽  
Meletios A. Dimopoulos ◽  
Wan-Jen Hong ◽  
Scott Cooper ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Survival ◽  
Residual Disease ◽  
Performance Status ◽  
Phase Iii ◽  
Survival Duration ◽  
Open Label ◽  
Once Daily ◽  
Refractory Multiple Myeloma ◽  
Patient Reported

TPS8554 Background: BCL-2 is an anti-apoptotic protein important for myeloma cell survival. Venetoclax (Ven) is a highly selective, potent, oral BCL-2 inhibitor, that has shown promise in clinical studies as monotherapy or in combination with other agents in patients with t(11;14)-positive relapsed/refractory multiple myeloma (RRMM; Kumar et al. Blood. 2017; Costa et al. ASH 2018. Abstr. #303; Harrison et al. ASH 2019. Abstr. #142; Bahlis et al. ASH 2019. Abstr. #925; Kaufman et al. ASH 2019. Abstr. #926). Notably, t(11;14)-positive MM is more dependent on BCL-2 for cell survival, which, together with these clinical data, suggests that Ven combined with dexamethasone (Dex) may provide greater clinical benefit versus standard therapies, like pomalidomide (Pom), in this biomarker-defined patient population. This ongoing Phase 3 study (CANOVA; NCT03539744) aims to evaluate the safety and efficacy of VenDex vs PomDex in t(11;14)-positive RRMM. Methods: Eligible patients (≥18 years) must have t(11;14)-positive RRMM per central lab, an ECOG performance status ≤2, received ≥2 prior lines of therapy, previously received a proteasome inhibitor, and must be refractory to lenalidomide and last line of therapy. Patients cannot have history of treatment with Ven, Pom, or other BCL-2 inhibitors. Patients will be randomized 1:1 to Ven (800 mg orally, once-daily) or Pom (4 mg orally, once-daily on days 1-21 of 28-day cycles). Patients in both groups will receive 40 mg Dex (20 mg for patients ≥75 years) once weekly. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal from study. Patients will be stratified based on age at randomization ( < 65 vs ≥65 years), prior lines of therapy (2 to 3 vs ≥4), and International Staging System stage at screening (I vs II vs III). The primary endpoint is progression-free survival (PFS) per independent review committee (IRC) assessment based on International Myeloma Working Group criteria. The final PFS analysis will be performed when approximately 147 PFS events per IRC are observed. Secondary endpoints are response rate, patient-reported outcomes, overall survival, duration of response, times to response and progression, minimal residual disease negativity rate, safety, and Ven pharmacokinetics. Approximately 244 patients will be enrolled; as of January 21, 2020, 28 patients have been randomized (from 19 sites in 12 countries) and enrollment is ongoing. Clinical trial information: NCT03539744 .

scholarly journals Characterization of Patient-Reported Outcomes in Multiple Myeloma Registrational Trials Submitted to the U.S. FDA

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Laura Fernandes ◽  
Jiaxi Zhou ◽  
Bellinda L King-Kallimanis ◽  
Thomas Gwise ◽  
Paul Kluetz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Patient Reported Outcomes ◽  
Core Outcome Set ◽  
Core Outcome ◽  
Outcome Set ◽  
Patient Reported ◽  
Assessment Frequency ◽  
Definition Of ◽  
Collection Methods

Introduction Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells. The US Food and Drug Administration (FDA) has approved numerous therapies for the treatment of MM over the past 13 years. During the same time period, there have been advances in characterizing the patient experience in oncology clinical trials, primarily using patient-reported outcomes (PRO). Although there have been advances in MM and collection of patient experience in clinical trials, this review aims to provide details on the heterogeneity of PRO measures and data analyses used in MM registrational trials. Methods We reviewed FDA databases for NDA/BLA submissions supporting therapies to treat patients with MM between 2007 and 2020. Pivotal trial protocols, clinical study reports, and FDA clinical/ statistical reviews supporting each application were reviewed for descriptions of included PROs. We focused on PRO measures, collection methods, baseline definition, assessment frequency, compliance, definition of thresholds for clinically meaningfulness, and statistical methods for analysis of PRO. Results We examined the results from 25 clinical trials that led to 20 new indications. PRO data were included in 17 of the 25 trials (68%). Of the 17 trials with PRO data, three were single arm trials, and the remainder were randomized trials. All trials were open label except for one blinded randomized trial. Seven trials collected data electronically, five in paper format, and five trials did not specify the collection format. The majority of trials had at least two PRO measures (82%) with two trials (12%) utilizing four measures. Among trials included for analysis, nine unique PRO measures were used, most commonly the EORTC QLQ-30 (87%), EQ-5D (65%), both cancer agnostic and QLQ-MY20 (47%), specifically for MM patients. We found differences in terms of definition of baseline. One trial defined measurements taken only at screening as the baseline assessment, while the remainder defined baseline as any measurement taken on or before day 1 cycle 1. Assessment frequency was highly variable (e.g. every cycle, every other cycle, every three months) and was largely dependent on cycle length (ranged from 21 to 42 days). We also noted that assessment may have been after a period of drug washout (e.g. the anti-MM regimen was administered on days 1-21 of a 28 day cycle; PRO assessment occurred on day 1 of the next cycle, thus following a 7-day washout). Definition of compliance of the PRO measures varied across the trials ranging from "completing all items" (6%), "completing 50% of the items" (12%), and "completing enough items to calculate the score in any domain" or some variant (82%). There was variability in the definition and justification of clinically meaningful thresholds across trials despite use of the same instrument and similar MM populations. Differences in statistical methods used for analyses of the PRO endpoints were also noted when analyzing data from the same measure across trials. For example, one of the two trials using the BPI-SF analyzed pain severity and intensity as composite endpoints (change from baseline analysis using a mixed model with treatment arm, time point, and baseline score as covariates). The other trial using the BPI-SF used pain response which was defined as a 30% reduction from baseline in worst pain score over the last 24 hours without an increase in analgesic use at 2 consecutive evaluations as an endpoint, and used the stratified Cochran-Mantel-Haenszel test to report treatment differences. Conclusions We encountered substantial heterogeneity in terms of PRO collection methods, measures, definitions and analyses in recent MM registrational trials. These differences may hinder the utility of this data for healthcare policy as well as clinician and patient decision making. FDA has proposed a core outcome set to be included in cancer clinical trials which includes assessment of patient-reported adverse events, disease symptoms, physical function, role function, and overall side effect bother. Use of this core outcome set in future MM registration trials is one step towards consistency in PRO collection and analysis. Further work needs to be done to determine the best approach for statistical and analytical methodologies. Table Disclosures No relevant conflicts of interest to declare.

scholarly journals Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gabriel Tremblay ◽  
Patrick Daniele ◽  
Janis Breeze ◽  
Lingling Li ◽  
Jatin Shah ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Nuclear Export ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Difference Threshold ◽  
Open Label ◽  
Ecog Ps

Abstract Background Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy – Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM. Methods FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders. Results Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores. Conclusion The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach. Trial registration This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015.

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