Patient-Reported Quality of Life In Elderly, Newly Diagnosed Multiple Myeloma Patients Treated with Bortezomib-Based Regimens: Results From the Phase 3b UPFRONT Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3026-3026 ◽  
Author(s):  
Ruben Niesvizky ◽  
Ian W. Flinn ◽  
Robert M. Rifkin ◽  
Nashat Y Gabrail ◽  
Veena Charu ◽  
...  
Keyword(s):  
Health Status ◽  
Global Health ◽  
Treatment Period ◽  
Research Funding ◽  
Global Health Status ◽  
Status Score ◽  
Patient Reported ◽  
Equity Ownership ◽  
Eortc Qlq ◽  
Health Status Score

Abstract Abstract 3026 Background: UPFRONT is an ongoing US community-based phase 3b study designed to compare the safety and efficacy of three bortezomib (Velcade®, Vc)-based regimens, Vc-dexamethasone (VcD), Vc-thalidomide-dexamethasone (VcTD), and Vc-melphalan-prednisone (VcMP), followed by Vc maintenance therapy, in previously untreated multiple myeloma (MM) patients who were ineligible for high-dose therapy and autologous stem cell transplantation (HDT-SCT). Efficacy data have been presented elsewhere; here we present patient-reported quality of life (QoL) data after 300 patients had the opportunity to undergo the entire 13-cycle treatment period (8 Vc-based induction cycles and 5 Vc maintenance cycles). Methods: Patients with symptomatic, measurable MM were randomized (1:1:1) to receive 49 weeks of therapy: 24 weeks (eight 21-day cycles) of induction with VcD, VcTD, or VcMP (VcD: Vc 1.3 mg/m2, days 1, 4, 8, 11; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]); VcTD: Vc 1.3 mg/m2, days 1, 4, 8, 11; T 100 mg/d, d1–21; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]); VcMP: Vc 1.3 mg/m2, days 1, 4, 8, 11; M 9 mg/m2, and P 60 mg/m2, day 1–4, every other cycle), followed by 25 weeks (five 35-day cycles) of maintenance with Vc alone (1.6 mg/m2, days 1, 8, 15, 22). Patient-reported QoL was recorded using the EORTC QLQ-C30 questionnaire, which assesses global health status, physical, role, cognitive, emotional, and social functions, fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Patients completed the questionnaire prior to dosing on cycle 1, day 1 (baseline), prior to dosing on day 1 of every odd cycle, at the end of treatment visit, and every 12 weeks thereafter. Here we present updated study results after 300 patients had the opportunity to undergo the entire 13-cycle treatment period, focusing on change in global health status score over time; no adjustment was made for missing cases or patient deaths. Results: Patient baseline characteristics were well balanced across the three treatment arms. Patients in the VcD, VcTD, and VcMP arms had median ages of 73.5, 73.0, and 72.0 years, respectively; 85%, 64%, and 74% had ISS stage II/III; 22%, 27%, and 28% were non-Caucasian; and 51%/25%/24%, 55%/30%/14%, and 62%/24%/15% had Charlson comorbidity index 0/1/≥2 in the VcD, VcTD, and VcMP arms, respectively. Patients received a median of 9 (VcD), 6 (VcTD), and 7 (VcMP) treatment cycles (induction + maintenance); 56%, 33%, and 43% of patients, respectively, received Vc maintenance. In the VcD, VcTD, and VcMP arms, Vc dose intensity (mean ratio of doses received/doses planned) was 76%, 63%, and 69% during induction, and 73%, 77%, and 85% during maintenance, respectively. After 13 treatment cycles, the rates of grade ≥3 adverse events (AEs) were 74%, 86%, and 80% in the VcD, VcTD, and VcMP arms. The incidence of serious AEs was highest in the VcTD arm (61%, vs 57% and 51% with VcD and VcMP), as was the rate of study drug discontinuation due to AEs (41%, vs 29% and 35% with VcD and VcMP). Global health status score by cycle is shown in the Figure, with number of patients with available QoL data in each arm indicated below. In all three arms, for those patients with available QoL data, global health status score at the end of cycle 12 was greater than at baseline and at the end of cycle 8 (end of Vc-based induction therapy). In the induction phase, global health status score remained stable in the VcD arm and transiently decreased in the VcMP arm at cycle 4, before increasing to above baseline levels. A similar trend was seen for the VcTD arm; global health status score started decreasing at cycle 2 but took slightly longer to increase, possibly due to the increased incidence of AEs in the VcTD arm. Similar trends were seen for other EORTC QLQ-C30 function and symptom scores. Conclusions: Although there was some variability during the study, by the end of the treatment period patients who received one of the three Vc-based regimens reported improvements in QoL compared with baseline values. The study is ongoing and patients continue to be followed for assessment of patient-reported QoL and long-term outcomes. Updated QoL data, including the correlation between change in QoL and best response achieved, will be presented. Disclosures: Niesvizky: Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding; Onyx: Consultancy, Research Funding. Off Label Use: Discussion of Velcade in a novel combination in frontline myeloma is included. Flinn:Millennium Pharmaceuticals, Inc.: Research Funding. Rifkin:Millennium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau; Cephalon: Speakers Bureau; Dendreon: Speakers Bureau. Gabrail:Millennium Pharmaceuticals, Inc.: Research Funding. Charu:Amgen: Equity Ownership, Research Funding; Pfizer: Equity Ownership; GSK: Equity Ownership, Research Funding; Lilly: Equity Ownership, Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Roche: Research Funding; Bristol-Myers Squibb: Equity Ownership. Neuwirth:Millennium Pharmaceuticals, Inc.: Employment. Corzo:Millennium Pharmaceuticals, Inc.: Employment. Reeves:Celgene: Equity Ownership.

scholarly journals Correlation between MPN-SAF TSS and EORTC QLQ-C30 Scores in Patients with PV: Data from the Reveal Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2259-2259 ◽  
Author(s):  
Ivy Altomare ◽  
Aaron T. Gerds ◽  
David Lessen ◽  
Philomena Colucci ◽  
Shreekant Parasuraman ◽  
...  
Keyword(s):  
Health Status ◽  
Global Health ◽  
Research Funding ◽  
Symptom Burden ◽  
Global Health Status ◽  
Employment Equity ◽  
Eortc Qlq C30 ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Introduction Polycythemia vera (PV) is characterized by clonal proliferation of myeloid cells and erythrocytosis. Patients with PV often present with symptoms or develop symptoms that may negatively impact quality of life (QOL). In clinical trials, the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) have both been used to assess symptom burden in patients with PV. This analysis was conducted in patients with PV enrolled in REVEAL, a multicenter, prospective, observational trial, in an attempt to corroborate previous work by Emanuel et al (J Clin Oncol 2012;30:4098), which demonstrated associations between the MPN-SAF TSS and EORTC QLQ-C30. Methods Patients ≥ 18 years of age with PV were enrolled and followed during usual care visits for ≤ 36 months. Patient-reported outcomes, including the MPN-SAF TSS and EORTC QLQ-C30, were collected at enrollment and at approximate 3-month intervals; only the forms completed at the time of enrollment were included in this analysis. MPN-SAF TSS items are scored on a linear analog scale ranging from 0 (absent) to 10 (worst imaginable), and individual symptom scores were added together to calculate a TSS; higher scores represent worse symptom burden. In the EORTC QLQ-C30, 28 questions are scored using a 4-point scale indicating frequency: 1 (not at all), 2 (a little bit), 3 (quite a bit), and 4 (very much); this includes 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Two questions on overall health and QOL are rated on a 1 (very poor) to 7 (excellent) scale. Five multi-item functional scales (physical, role, cognitive, emotional, and social), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), and a multi-item global health status/QOL scale are derived from the 30 questions. Linear transformation to 0-100 was applied to raw scores to obtain scores for each scale or single item. Higher scores for functional scales and global health status represent higher functioning and better health status/QOL, respectively. Higher scores for symptom scales/items represent higher symptom burden. Pearson correlation coefficient was used to assess correlations between MPN-SAF TSS and EORTC QLQ-C30 scales. Results As of data cutoff (April 30, 2018), 2,298 of 2,510 enrolled patients (91.6%) had completed both MPN-SAF TSS and EORTC QLQ-C30 forms at enrollment. Median age was 67 years (range, 22-97 years), 54.0% were male, and 89.7% were Caucasian. Median disease duration at the time of enrollment was 4.1 years. The majority (52.5%) of patients were treated with hydroxyurea (28.7%) or hydroxyurea with phlebotomy (23.8%). The mean MPN-SAF TSS was 18.7 (out of 100) compared to 21.8 reported by Emanuel et al 2012. The 4 symptoms with the highest mean scores were fatigue (3.5), early satiety (2.6), inactivity (2.5), and itching (2.3). The QLQ-C30 mean scores for overall QOL and health were 5.5 and 5.3, respectively. EORTC QLQ-C30 symptom scales were highest for fatigue (29.9), insomnia (28.7), and pain (20.0). Correlation between MPN-SAF TSS and EORTC QLQ-C30 results showed stronger associations between multiple items (Table). Calculated TSS had the strongest association with fatigue (r = 0.72), pain (r = 0.59), cognitive functioning (r = -0.58), and emotional functioning (r = -0.58). Problems with concentration in the MPN-SAF TSS was moderately correlated with cognitive functioning (r = -0.70) in the EORTC QLC-C30. Fatigue assessments were also moderately correlated (r = 0.65) between the MPN-SAF TSS and EORTC QLQ-C30. Conclusions In this analysis of prospectively gathered real-world data, the MPN-SAF TSS results confirm that patients with PV experience a recognizable constellation of symptoms, including fatigue, early satiety, inactivity, and itching. Not surprisingly, PV-related symptoms have a negative impact on QOL. There were moderate correlations (r = 0.5-0.75) between the MPN-SAF TSS and the EORTC QLC-C30 with respect to global health status/QOL, the 5 functional scales, and fatigue, pain, and dyspnea. Consistent with the previous analysis, this analysis provides further evidence that the MPN-SAF TSS represents an accurate, yet simple tool to assess PV-related symptoms and their potential impact on QOL. Disclosures Altomare: Novartis: Consultancy; Incyte: Consultancy; Amgen: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Celgene: Other: Advisory Board Member; Ipsen: Other: Advisory Board Member. Gerds:Celgene: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Lessen:Abbvie: Honoraria; Teva: Honoraria, Speakers Bureau; Incyte: Honoraria, Research Funding, Speakers Bureau; Astellas: Research Funding; Bayer: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Portola: Honoraria, Speakers Bureau; Janssen: Research Funding. Colucci:Incyte: Employment, Equity Ownership. Parasuraman:Incyte: Employment, Equity Ownership. Paranagama:Incyte: Employment, Equity Ownership. Mesa:Pfizer: Research Funding; Incyte Corporation: Research Funding; Gilead: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Celgene: Research Funding; Novartis: Consultancy; UT Health San Antonio - Mays Cancer Center: Employment; CTI Biopharma: Research Funding; Genentech: Research Funding.

scholarly journals Disease Burden Subgroup Analysis of Health-Related Quality of Life of Blinatumomab Versus Standard-of-Care Chemotherapy in Patients with Relapsed or Refractory Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia in a Randomized, Open-Label Phase 3 Study (TOWER)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3967-3967
Author(s):  
Anthony S. Stein ◽  
Zachary F. Zimmerman ◽  
Paul Cannell ◽  
Hervé Dombret ◽  
Johan Maertens ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Health Status ◽  
Global Health ◽  
Research Funding ◽  
Disease Burden ◽  
Employment Equity ◽  
Eortc Qlq C30 ◽  
Equity Ownership ◽  
Eortc Qlq ◽  
Baseline Hrqol

Abstract Background: In the phase 3 TOWER study, patients with relapsed or refractory (r/r) Philadelphia chromosome-negative (Ph-) B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) who received bispecific T-cell engager (BiTE®) antibody construct blinatumomab had improved overall survival (OS; median, 7.7 vs 4.0 months; P=0.01;) and health-related quality of life (HRQoL) compared with those who received standard of care (SOC) chemotherapy (Kantarjian H, et al. N Engl J Med. 2017;376:836-847; Topp MS, et al. Blood. 2018;131:2906-2914). In this subgroup analysis of TOWER, we assessed the HRQoL between patients with low versus high baseline disease burden (low versus high bone marrow blast levels) who received blinatumomab or SOC chemotherapy. Methods: Patients (N=405) with r/r Ph- BCP ALL were randomized 2:1 to receive 2 cycles of induction blinatumomab by continuous intravenous infusion (n=271) or SOC (n=134). Those in remission could receive up to 3 consolidation cycles; 12 months of maintenance was allowed for those who received up to 3 consolidation cycles and had bone marrow response. HRQoL was assessed using the EORTC QLQ-C30 Questionnaire on days 1 (baseline), 8, and 15; on day 29 of cycle 1; days 1, 15, and 29 of consolidation; and at the safety follow-up. The questionnaire included 1 global health status scale, 5 functioning scales, 3 symptom scales, and 6 single-symptom items. For global health status and functioning scales, a higher score indicates better HRQoL; for symptom scales/items, a lower score indicates better HRQoL. A 10-point change was viewed as the minimum clinically important difference in EORTC QLQ-C30 (Zikos E, et al. EORTC. 2016). HRQoL was assessed in patient subgroups by screening the bone marrow aspirates for low blast levels (<50% blasts) versus high blast levels (≥50% blasts). Although blast count was not a randomization stratification factor in TOWER, baseline HRQoL values were assessed for blinatumomab versus SOC in both subgroups; in the high blasts group, for blinatumomab versus SOC, the only differences were cognitive functioning and constipation scores, which were significantly higher, and for the diarrhea score, which was significantly lower. Between the subgroups, only physical functioning was significantly different (higher in the high blasts group). Analyses included patients with baseline and ≥1 postbaseline result of any multi-item scale or single-item measure. Mean change from baseline in scores for each scale/item were summarized for cycle 1. Time to deterioration (TTD) analyses assessed the treatment effect based on timing from the initiation of treatment to a 10-point deterioration from baseline. Results: In total, 342 patients (blinatumomab, n=247; SOC, n=95) had ≥1 HRQoL result: low blasts, n=87 (blinatumomab, n=64; SOC, n=23); high blasts, n=255 (blinatumomab, n=183; SOC, n=72). The EORTC QLQ-C30 analysis set included all randomized subjects with a nonmissing baseline result and at least 1 nonmissing post-baseline result of any EORTC QLQ-C30 scale/item. There was no statistically significant difference in baseline HRQoL scores between the high and low blasts groups; however, the high blasts group had worse HRQoL overall. Baseline HRQoL scores were also similar between blinatumomab arm and SOC arm for each group. Global health status was improved by blinatumomab regardless of baseline blast level; however, this effect was somewhat greater in the low blasts group. When the function scores worsened, the extent of worsening was almost always smaller for blinatumomab versus SOC, particularly in the high blasts group. Functioning status scores tended to stay the same or worsen with both blinatumomab and SOC regardless of blast level, except emotional scores, which improved with blinatumomab regardless of blast level (Figure 1). Symptom scores generally improved with blinatumomab but not with SOC, particularly in patients with high blasts (Figure 2). TTD analyses showed that hazard ratios favored blinatumomab over SOC, particularly in patients with high blasts (Table). Conclusions: Blinatumomab improved HRQoL in patients with r/r Ph- BCP ALL and delayed the time to clinically meaningful deterioration in HRQoL compared with SOC. The treatment effects of blinatumomab versus SOC on HRQoL were particularly larger among patients with high disease burden. Disclosures Stein: Amgen Inc.: Speakers Bureau; Celgene: Speakers Bureau. Zimmerman:Amgen Inc.: Employment, Equity Ownership. Dombret:Novartis: Consultancy, Honoraria, Research Funding; Agios: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria; Ambit (Daiichi Sankyo): Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Menarini: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria, Other: Travel expenses; Celgene: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Immunogen: Consultancy, Honoraria; Shire-Baxalta: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharma: Consultancy, Honoraria, Research Funding; Ariad (Incyte): Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Roche/Genentech: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau. Topp:F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Boehringer Ingelheim: Research Funding. Franklin:Amgen Inc.: Employment, Equity Ownership. Cong:Amgen, Inc.: Employment, Equity Ownership. Zhang:Amgen Inc.: Employment, Equity Ownership. Schuh:Pfizer: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Teva: Consultancy; Amgen Inc.: Consultancy; Otsuka: Consultancy; Jazz: Consultancy; Shire: Consultancy.

Effect of the Terminal Complement Inhibitor Eculizumab on Patient Reported Outcomes in Paroxysmal Nocturnal Hemoglobinuria (PNH): Phase III Triumph Study Results.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3770-3770 ◽  
Author(s):  
Robert A. Brodsky ◽  
Petra Muus ◽  
Ulrich Dührsen ◽  
Anita Hill ◽  
Monica Bessler ◽  
...  
Keyword(s):  
Health Status ◽  
Global Health ◽  
Patient Reported Outcomes ◽  
Global Health Status ◽  
Intravascular Hemolysis ◽  
Patient Functioning ◽  
Patient Reported ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Terminal Complement

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia in which complement-sensitive RBCs are destroyed leading to chronic intravascular hemolysis. PNH patients suffer from diverse and serious hemolysis-induced morbidities leading to a poor quality of life (QoL). Fatigue in PNH patients may be disabling and levels are similar to anemic cancer patients. Fatigue is multifactoral, related to both the underlying anemia and hemolysis. Patients suffer from reduced global health status, patient functioning, pain and dyspnea. Treatment with the terminal complement inhibitor eculizumab reduces intravascular hemolysis and improves anemia. The impact of eculizumab treatment on levels of fatigue and other patient reported outcomes was prospectively examined in a double-blind placebo controlled study (TRIUMPH) using two distinct instruments, the FACIT-Fatigue and the EORTC QLQ-C30. Improvements in QoL were quantified using standardized effect sizes (SES), a measure of the magnitude of the clinical benefit in various instruments. Eculizumab treatment, as compared to placebo, was associated with a very large and significant improvement in fatigue as measured by the FACIT-Fatigue scale (SES=1.13, P<0.001) as well as the EORTC QLQ-C30 fatigue subscale (SES=1.12, P<0.001). Similarly, the percentage of patients achieving a pre-specified minimally important difference (MID) was 53.7% versus 20.5% of eculizumab- and placebo-treated patients, respectively (P=0.003) using the FACIT-Fatigue; 67.7% versus 24.4%, respectively (P<0.001) with the EORTC QLQ-C30. Treatment independent univariate analyses showed that reduction in intravascular hemolysis (decreased LDH levels) and improvement in anemia (increased hemoglobin levels) were both significantly associated with an improvement in fatigue. Further, multivariate analyses indicated that reduction in hemolysis was more predictive than improvement in anemia of an improvement in fatigue. Eculizumab treatment was also associated with significant improvements with moderate to large SES in the following EORTC QLQ-C30 subscales: global health status (0.87, P<0.001); role functioning (0.93, P<0.001); social functioning (0.57, P=0.003); cognitive functioning (0.78, P=0.002); physical functioning (1.01, P<0.001); emotional functioning (0.51, P=0.008); pain (0.65, P=0.002); dyspnea (0.69, P<0.001); and appetite loss (0.50, P<0.001). These data demonstrate that resolution of intravascular hemolysis with eculizumab treatment results in large and clinically meaningful improvements in patient reported outcomes including fatigue, global health status, patient functioning, and disease-related symptoms in PNH.

Patient-Reported Quality of Life (QoL) in Elderly, Newly Diagnosed Multiple Myeloma (MM) Patients Receiving Bortezomib-Based Combinations: Results From All Randomized Patients in the Community-Based, Phase 3b UPFRONT Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1864-1864 ◽  
Author(s):  
Ruben Niesvizky ◽  
Ian W. Flinn ◽  
Robert Rifkin ◽  
Nashat Gabrail ◽  
Veena Charu ◽  
...  
Keyword(s):  
Health Status ◽  
Global Health ◽  
Board Of Directors ◽  
Research Funding ◽  
Global Health Status ◽  
Linear Mixed Effect Model ◽  
Advisory Committees ◽  
Mixed Effect ◽  
Linear Mixed Effect ◽  
Patient Reported

Abstract Abstract 1864 Background: In addition to determining the efficacy and safety of different treatment options for MM, the impact of treatment and associated toxicities on patient-reported QoL should be evaluated. The US community-based phase 3b UPFRONT study compares the efficacy and safety of three bortezomib (VELCADE®, Vc)-based regimens, Vc-dexamethasone (VcD), Vc-thalidomide-dexamethasone (VcTD), and Vc-melphalan-prednisone (VcMP), followed by weekly Vc maintenance, in elderly, newly diagnosed, transplant-ineligible MM patients. Updated efficacy and safety data are reported elsewhere at this meeting; here we present patient-reported QoL results – a secondary endpoint of the trial – from all 502 randomized patients, who received up to a maximum of 13 treatment cycles. Methods: Patients with symptomatic MM were randomized (1:1:1) to receive eight 21-day cycles of VcD (Vc 1.3 mg/m2, days 1, 4, 8, 11; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]), VcTD (Vc as before; T 100 mg/day, days 1–21; D as before), or VcMP (Vc as before; M 9 mg/m2, and P 60 mg/m2, days 1–4, every other cycle) induction, followed by five 35-day cycles of maintenance with Vc 1.6 mg/m2, days 1, 8, 15, 22. QoL was assessed using the EORTC QLQ-C30 questionnaire, which includes global health status, physical, role, cognitive, emotional, and social functioning, and symptom scales of fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Global health status scores combine overall health and QoL scores, with higher scores reflecting better health status. Questionnaires were completed prior to dosing on day 1 of cycle 1 (baseline), prior to dosing on day 1 of every odd-numbered cycle, at the end-of-treatment visit, and every 12 weeks until progressive disease. Patient-reported QoL scores presented herein represent data collected within 1 year of randomization regardless of discontinuation status; for patients who died, missing assessments were assigned the worst possible score of 0. A linear mixed effect model was used to assess QoL changes over time, both within and between treatment arms. Sensitivity analyses were conducted to test the robustness of the primary analysis. Results: Patient baseline characteristics were well balanced across the VcD (n=168), VcTD (n=167), and VcMP (n=167) arms as reported previously (Niesvizky et al, EHA 2011). Median age was 74.5 (VcD), 73.0 (VcTD), and 72.0 (VcMP) years, and 71%, 62%, and 72% of patients had ISS stage II/III disease. QoL assessments were available at baseline and ≥1 post-baseline time point for 78% (VcD), 69% (VcTD), and 78% (VcMP) of patients. Observed data showed a downward trend in mean global health status score until cycle 7 (VcD, VcMP) or 9 (VcTD), followed by a trend to stabilizing/improving score thereafter (Figure). Symptom scores changed very little during induction in all arms, except for nausea/vomiting and diarrhea, with moderate improvements seen during maintenance. After fitting observed data with a linear mixed effect model, a significant decrease in mean global health status score from baseline to cycle 7 (induction period) was evident in all arms (VcD, p=0.0127; VcTD, p<0.0001; VcMP, p=0.0157), but there were no significant inter-arm differences. During cycles 9–13 (maintenance period), mean global health status scores remained decreased from baseline in the VcD and VcTD arms, and there were significant differences between VcTD and VcMP, with lower scores in the VcTD arm. Sensitivity analyses incorporating patients' QoL data collected after discontinuation of treatment (for patients who discontinued within 1 year) and utilizing a last observation carried forward approach, gave similar results to the linear mixed effect model. Conclusions: The observed data, linear mixed model estimates, and sensitivity analyses all show a common trend to a transient decrease in QoL during VcD, VcTD, and VcMP induction followed by a subsequent trend to improvement/stabilization in QoL during single-agent Vc maintenance. The trend to decreasing QoL seen during Vc-based induction may reflect the onset of treatment-related toxicities (particularly for VcTD, which was associated with somewhat higher toxicity rates). Post-induction improvements/stabilization in QoL may reflect the beneficial impact of achieving a response and the limited toxicity profile associated with weekly Vc maintenance. Disclosures: Niesvizky: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Research Funding. Flinn:Millennium Pharmaceuticals, Inc.: Research Funding. Rifkin:Onyx: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Millennium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Charu:Pfizer: Equity Ownership; Bristol-Myers Squibb: Equity Ownership; Roche: Research Funding; GSK: Research Funding; Celgene: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Neuwirth:Millennium Pharmaceuticals, Inc.: Employment. Huang:Millennium Pharmaceuticals, Inc: Employment. Choi:Millennium Pharmaceuticals, Inc.: Employment. Corzo:Millennium Pharmaceuticals, Inc.: Employment.

Changes in Quality of Life and Disease-Related Symptoms in Patients with Polycythemia Vera Receiving Ruxolitinib or Best Available Therapy: RESPONSE Trial Results

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 709-709
Author(s):  
Ruben Mesa ◽  
Srdan Verstovsek ◽  
Jean-Jacques Kiladjian ◽  
Martin Griesshammer ◽  
Tamas Masszi ◽  
...  
Keyword(s):  
Global Health ◽  
Board Of Directors ◽  
Research Funding ◽  
Symptom Burden ◽  
Global Health Status ◽  
Employment Equity ◽  
Advisory Committees ◽  
Eortc Qlq C30 ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Background : Polycythemia vera (PV) is a myeloproliferative neoplasm driven by JAK/STAT activation and is associated with erythrocytosis and a broad symptom burden that may negatively impact patient quality of life (QoL). Hydroxyurea (HU) is often used as first-line therapy for high-risk patients but may not effectively control or reduce symptom burden. RESPONSE is a phase III trial comparing ruxolitinib (RUX) with best available therapy (BAT) in patients with PV who were intolerant of or resistant to HU according to modified European LeukemiaNet (ELN) criteria. The primary study endpoint (a composite of hematocrit control and ≥35% spleen volume reduction at Week 32) was achieved by 21% of patients in the RUX arm vs 1% in the BAT arm (P<0.0001); 77% of patients in the RUX arm achieved at least one component of the primary endpoint. The current analysis was conducted to evaluate the effect of RUX on PV-related symptoms and QoL measures in the RESPONSE trial. Methods : Patients with PV aged ≥18 years, resistant to or intolerant of HU (modified ELN criteria) with splenomegaly, and who required phlebotomy for hematocrit control were randomized 1:1 to receive open-label RUX 10 mg twice daily (BID) or BAT (administered based on investigator judgment). Dose adjustments were permitted (RUX, 5-mg BID increments [25 mg BID max]; BAT was adjusted per investigator judgment). Objectives of this analysis included assessment of improvement in symptom burden as assessed by patient-reported outcomes using the 14-item modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Patient Global Impression of Change. The 14-item MPN-SAF (graded from 0 [absent] to 10 [worst imaginable]) comprised symptoms related to cytokines (tiredness, itching, muscle ache, night sweats, and sweats while awake), hyperviscosity (vision problems, dizziness, concentration problems, headache, numbness/tingling, ringing in ears, and skin redness), and splenomegaly (abdominal discomfort and early satiety). Changes in total symptom score (TSS; maximum score = 140) and individual symptom scores from baseline to Week 32 were summarized by treatment group. For the EORTC QLQ-C30 Global Health Status/QOL score, the percentage of patients with a minimally important difference (MID) from baseline (10-point change) at Week 32 was summarized. Results : Overall, 222 patients were randomized (RUX, 110; BAT, 112). Median age (range) was similar between arms (RUX, 62.0 [34.0–90.0]; BAT, 60.0 [33.0–84.0]); the RUX and BAT arms were 60% and 71% male, respectively. At Week 32, a higher proportion of patients in the RUX vs the BAT arms had a ≥50% improvement in MPN-SAF TSS (49% vs 5%, respectively) and MPN-SAF symptom cluster scores (cytokine, 64% vs 11%; hyperviscosity, 37% vs 13%; splenomegaly, 62% vs 17%). Median percentage changes in individual symptom scores are presented in the Table. Mean changes from baseline at Week 32 on the 5 items of the PSIS indicated that the severity of pruritus and its interference on daily life improved with RUX (range, −1.5 to −2.2) and was unchanged/worsened with BAT (range, −0.1 to 0.3). Treatment with RUX vs BAT was associated with improved mean changes from baseline at Week 32 on EORTC QLQ-C30 symptom subscales, functional subscales, and Global Health Status/QOL (Table); 46% of RUX patients versus 10% of BAT patients achieved an MID in Global Health Status/QOL (Figure). At Week 32, RUX patients were more likely to rate their global impression of symptom changes as “very much improved” or “much improved” (67%) vs BAT patients (13%). Conclusion : In patients with PV who were resistant to or intolerant of HU, treatment with RUX was associated with greater and clinically meaningful improvements in PV-related symptom burden and QoL measures compared with BAT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Mesa: Incyte Corporation: Research Funding; CTI: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Eli Lilly: Research Funding; Promedior: Research Funding; NS Pharma: Research Funding; Sanofi: Research Funding; Celgene: Research Funding. Off Label Use: Ruxolitinib is a JAK1/JAK2 inhibitor approved for the treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Verstovsek:Incyte Corporation: Research Funding. Kiladjian:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Masszi:Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Durrant:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Harrison:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. He:Incyte Corporation: Employment, Equity Ownership. Jones:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Li:Novartis Pharmaceuticals: Employment, Equity Ownership. Côté:Novartis Pharmaceuticals: Employment, Equity Ownership. Habr:Novartis Pharmaceuticals: Employment, Equity Ownership. Vannucchi:Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Patient-reported quality of life (QoL) of advanced melanoma patients in a Phase 3 study of nivolumab (NIVO) with or without ipilimumab (IPI) versus IPI: CheckMate 067 4-year data.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9551-9551
Author(s):  
Dirk Schadendorf ◽  
James M.G. Larkin ◽  
Jedd D. Wolchok ◽  
Vanna Chiarion-Sileni ◽  
Fiona Taylor ◽  
...  
Keyword(s):  
Health Status ◽  
Global Health ◽  
Mixed Model ◽  
Advanced Melanoma ◽  
Global Health Status ◽  
Mixed Model Analysis ◽  
Patient Reported ◽  
Eortc Qlq C30 ◽  
Eortc Qlq

9551 Background: Early CheckMate 067 data showed maintenance of QoL in patients with advanced melanoma treated with NIVO with or without IPI based on 1-year data; however, the long-term QoL of these patients has not been evaluated previously. The patient-reported outcomes (PRO) analyses presented here for CheckMate 067 is the first time QoL results have been evaluated in this melanoma population over a 4-year period. Methods: In CheckMate 067, 945 patients were randomized 1:1:1 to receive NIVO (3mg/kg Q2W) + placebo (PBO), NIVO+IPI (1mg/kg+3mg/kg Q3W X 4) followed by NIVO (3mg/kg Q2W), or IPI (3mg/kg Q3W X 4) + PBO. PRO data were collected using the EORTC QLQ-C30 (5 functional domains, 9 symptoms, global health status) and EQ-5D-3L (utility index, VAS) at baseline, weeks 1 and 5 of each 6-week tx cycle, and off-tx follow-up (FU) visits. Mean changes in PRO scores from baseline (randomization) were evaluated descriptively for the PRO analysis population, with conclusions drawn from time points with ≥30 patients completing assessments per tx arm. Least square mean changes from baseline were assessed using a longitudinal mixed model analysis adjusting for repeated measures, including all on-tx data for patients. Results: Completion rates at baseline ranged from 89-92% across tx arms. Of 813 patients included in the PRO analysis population (278 NIVO, 274 NIVO+IPI, 261 IPI), > 200 receiving tx remained for the first year, > 100 receiving tx remained after 2 years, and > 50 receiving tx remained after 3 years. QoL, including assessment of functioning and symptom burden, was maintained for the duration of tx and in FU, with no sustained clinically meaningful deterioration in any tx arm. Global health status (EORTC QLQ-C30) and general QoL (EQ-5D-3L VAS) were also maintained during prolonged tx. Overall, results from the mixed model analysis support the long-term maintenance of QoL over the course of tx. Conclusions: Patient-reported QoL and symptoms in patients with advanced melanoma were maintained from baseline during extended tx with NIVO with or without IPI. Clinical trial information: NCT01844505.

Pomalidomide (POM) Plus Low-Dose Dexamethasone (LoDEX) Improves Health-Related Quality Of Life (HRQoL) Vs High-Dose Dexamethasone (HiDEX) In Relapsed Refractory Multiple Myeloma (RRMM) Patients Enrolled In MM-003 Phase 3 Randomized Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2939-2939 ◽  
Author(s):  
Kevin W. Song ◽  
Meletios A. Dimopoulos ◽  
Katja Weisel ◽  
Michel Delforge ◽  
Lionel Karlin ◽  
...  
Keyword(s):  
Health Status ◽  
Global Health ◽  
Board Of Directors ◽  
Physical Functioning ◽  
Research Funding ◽  
Emotional Functioning ◽  
Global Health Status ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Abstract Background Pronounced symptoms, poor prognosis, and therapy exhaustion each affect HRQoL in RRMM patients. The MM-003, randomized, multicenter, open-label phase 3 trial reported that POM + LoDEX significantly extended median progression-free and overall survival vs HiDEX in RRMM patients who exhausted bortezomib (BORT) and lenalidomide (LEN), and progressed on their last treatment (San Miguel, EHA, 2013). Improved survival outcomes, treatment-related toxicity, and aging populations have placed an emphasis on HRQoL in RRMM. MM-003 is the first study to investigate HRQoL in RRMM patients treated with POM + LoDEX. Methods Patients were randomized 2:1 to receive 28-day cycles (C) of POM 4 mg D1-21 + LoDEX 40 mg (20 mg for patients aged > 75 years) weekly or HiDEX 40 mg (20 mg for patients aged > 75 years) D1-4, 9-12, and 17-20 until disease progression or unacceptable toxicity. HiDEX was chosen as the comparator to isolate the effects of POM as at the time of trial design, it was the standard salvage therapy for heavily pretreated patients. Time to meaningful worsening in HRQoL was analyzed for 5 predefined EORTC QLQ-C30 domains (Global Health Status, Physical Functioning, Fatigue, Emotional Functioning, and Pain) using the Kaplan-Meier method. A meaningful worsening was defined as a reduction in HRQoL equal to or greater than the domain-specific minimally important difference, calculated using the standard error of measurement. HRQoL was also evaluated cross-sectionally and longitudinally through a mixed effect model. Data from the September 7, 2012 data cut are presented below. Results 455 patients were randomized to POM + LoDEX (n = 302) or HiDEX (n = 153). 448 patients completed at least 1 QLQ-C30 questionnaire and were included in the HRQoL analysis. The median number of prior treatments was 5 (range, 2-17), and 82% were refractory to LEN and BORT. Median follow-up was 4.2 months. Analyses on time to clinically meaningful worsening showed that POM + LoDEX extended median time to meaningful worsening vs HiDEX for all the preselected domains (Table): Global Health Status (114 vs 85 days, P = .06), Physical Functioning (174 vs 106 days; P = .09), Fatigue (113 vs 60 days; P = .04), Emotional Functioning (190 vs 124 days; P = .02), and Pain (147 vs 113 days; P = .2). In the cross-sectional analysis, HRQoL scores were relatively better for POM + LoDEX vs HiDEX for all domains at every cycle. Statistically or marginally significant (P < .10) treatment differences were observed for Global Health Status (C2 and 4), Physical Functioning (C2, 3, and 4), Emotional Functioning (C3), and Fatigue (C2) domains. No statistically significant deteriorations from baseline were observed in the mean scores for the POM + LoDEX arm for any of the 5 domains at any treatment cycle. Such deteriorations were observed with HiDEX. These results were supported by a mixed effect model analysis. Data from the March 1, 2013 data cut will be presented at the meeting. Conclusions In heavily pretreated patients who exhausted BORT and LEN, POM + LoDEX resulted in better clinical outcomes and favorable HRQoL vs patients treated with HiDEX. POM + LoDEX should become a standard of care in relapsing patients as it has been proven to prolong and enhance the lives of RRMM patients. Disclosures: Song: Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Off Label Use: POM is approved in the US but not in Europe. Dimopoulos:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Weisel:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria. Delforge:Celgene: Honoraria. Karlin:Celgene: Export board committee Other, Honoraria; Janssen: Honoraria. Goldschmidt:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Moreau:Celgene: Honoraria, Speakers Bureau. Oriol:Celgene: Consultancy. Spencer:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Knop:Celgene: Honoraria. Renner:Celgene: Consultancy, Honoraria, Travel support Other. Bahlis:Celgene: Consultancy, Honoraria, Research Funding. Amatya:Celgene: Consultancy. Yu:Celgene: Employment, Equity Ownership. Monzini:Celgene: Employment, Equity Ownership. Sternas:Celgene: Employment, Equity Ownership. Zaki:Celgene: Employment, Equity Ownership. Jacques:Celgene: Employment, Equity Ownership. San Miguel:Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

FOENIX-CCA2 quality of life data for futibatinib-treated intrahepatic cholangiocarcinoma (iCCA) patients with FGFR2 fusions/rearrangements.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4097-4097
Author(s):  
Juan W. Valle ◽  
Antoine Hollebecque ◽  
Junji Furuse ◽  
Lipika Goyal ◽  
Funda Meric-Bernstam ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Health Status ◽  
Global Health ◽  
Global Health Status ◽  
Phase 2 ◽  
Life Data ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
Eq Vas

4097 Background: In FOENIX-CCA2 (NCT02052778), a pivotal phase 2 study among iCCA patients (pts) with FGFR2 fusions/rearrangements, the highly selective, irreversible FGFR1–4 inhibitor futibatinib demonstrated a confirmed objective response rate of 41.7%, with a 9.7-month median duration of response. Adverse events were manageable with dosing modifications that did not adversely impact on response. We report outcomes for the preplanned analysis of Patient-Reported Outcomes (PROs) during futibatinib treatment as a secondary objective of FOENIX-CCA2. Methods: Pts enrolled in FOENIX-CCA2 had locally advanced/metastatic unresectable iCCA with FGFR2 fusions/rearrangements, ≥1 prior line of therapy (including gemcitabine/cisplatin) and ECOG PS 0-1. Pts received oral futibatinib 20 mg continuous QD dosing per 21-day cycle. PRO measures included EORTC-QLQ-C30 (1 global health, 5 functional, 9 symptom scales), EQ-5D-3L, and EQ visual analogue scale (VAS). PROs were collected at screening, cycles 2 and 4, every 3 cycles thereafter, and end of treatment. PRO data were evaluated up to cycle 13, the last visit before data were missing for >50% of the PRO population (PRO primary assessment time point). Results: 92/103 (89.3%) pts enrolled had PRO completion data at baseline and a minimum of 1 follow-up assessment (median age 58 y, 56.5% female), with 48 pts having PRO data at cycle 13. At baseline, mean (SD) EORTC QLQ-C30 global health status score was 70.1 (19.4) and EQ VAS score 71.7 (20.3). Mean EORTC QLQ-C30 global health status scores were maintained from baseline to cycle 13, corresponding to 9.0 months on treatment, with no clinically meaningful (≥10-point) changes in individual functional measures (Table). EORTC QLQ-C30 scores across individual symptom measures were also stable from baseline through cycle 13; only constipation showed an average of 10.0-point worsening at only cycle 4. Mean EQ VAS scores were sustained from baseline to cycle 13 (mean change ranging -1.8 to +4.8 across cycles), with values maintained within the population norm range from across 20 countries. Conclusions: Quality of life data from the phase 2 FOENIX-CCA2 trial show that physical, cognitive and emotional functioning, and overall health status were maintained among pts with advanced iCCA receiving futibatinib. Clinical trial information: NCT02052778. [Table: see text]

scholarly journals Improvements in Health-Related Quality of Life and Symptoms in Patients with Previously Untreated Chronic Lymphocytic Leukemia: Final Results from the Phase II GIBB Study of the Combination of Obinutuzumab and Bendamustine

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3491-3491 ◽  
Author(s):  
Alexey Danilov ◽  
Habte A Yimer ◽  
Michael Boxer ◽  
John M Burke ◽  
Sunil Babu ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Health Status ◽  
Chronic Lymphocytic Leukemia ◽  
Global Health ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Future Health ◽  
Equity Ownership

Introduction: Longitudinal changes in health-related quality of life (HRQoL) are important in patients with chronic lymphocytic leukemia (CLL). GIBB (NCT02320487) is an open-label, single-arm phase II study of obinutuzumab (GA101; G) in combination with bendamustine (G-Benda) in patients with previously untreated CLL. A previous report from the GIBB study demonstrated an investigator-assessed objective response rate of 89.2%, a complete response rate of 49.0%, and no unexpected safety signals with G-Benda (Sharman et al. J Clin Oncol 2017). Here we report the final HRQoL data over 3 years from the GIBB study. Methods: Enrolled patients received G-Benda by intravenous infusion over six 28-day cycles: G 100mg on Day (D)1, 900mg on D2, and 1000mg on D8 and D15 of Cycle (C)1, then 1000mg on D1 of C2-6; benda 90mg/m2 on D2-3 of C1, and on D1-2 of C2-6. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) includes a global health status measure, 5 functional scales (physical, emotional, cognitive, social, and role functioning), 8 symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, and diarrhea), and an item on financial difficulties (Aaronson et al. J Natl Cancer Inst 1993). The EORTC Quality of Life Questionnaire-Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) is a 16-item module, specific to CLL, containing 4 multi-item scales (fatigue, treatment side effects, disease symptoms, and infection) and 2 single items (social activities and future health worries). Both questionnaires were completed by patients on C1D1 (baseline), C3D1, and C6D1, at the end of induction (EOI) treatment (defined as +28 days from C6D1 or early treatment termination visit), at the response visit (defined as 2-3 months after the EOI treatment for all patients who received study treatment and had not experienced disease progression), and every 3 months thereafter at follow-up visits for up to 2 years. In total, there were 14 timepoints where data were collected. HRQoL scores were linear transformed to a 0-100-point scale. Mean baseline scores and mean score changes from baseline at each visit were evaluated. A threshold of ≥10-point change in score represents a clinically meaningful difference. For symptoms, negative change scores from baseline reflect an improvement in symptom burden. For global health status and functioning, positive change scores from baseline reflect improvements. Results: The trial enrolled 102 patients. Median age was 61 years and 68.4% of patients were male. Ninety-eight patients (96%) completed a questionnaire at baseline and at least 1 other questionnaire during a follow-up visit. Questionnaire completion rates at 14 time points ranged from 96% at baseline to 66% at 27 months follow-up (Table 1). According to the EORTC QLQ-C30 (Figure 1), improvements were observed for global health status at all follow-up visits, and clinically meaningful improvements were observed at the response visit, 3 months follow-up, and 27 months follow-up. Clinically meaningful improvements in role functioning were observed at EOI and persisted throughout the 27-month follow-up. For fatigue, clinically meaningful improvements were observed at every visit starting from the end of treatment (EOT) visit. Improvements were also observed for insomnia with mean reductions from baseline ≥10 points at various time points during follow-up. There was no worsening in other patient-reported symptoms or functional status over time. Similarly, with the EORTC QLQ-CLL16 (Figure 2), clinically meaningful improvements in symptoms were observed for fatigue, disease symptoms, and future health worries during treatment, at the EOT and/or throughout the follow-up. The largest improvement was observed for fatigue (-24.7) at the 24-month follow-up and future health worries (-25.4) at the 27-month follow-up. Conclusions: We previously reported that G-Benda is an effective regimen for first-line treatment of CLL with no unexpected safety signals. The HRQoL data from the GIBB trial suggest that G-Benda treatment consistently improved patient HRQoL over time. Several clinically meaningful improvements were observed in HRQoL, including global health status, functioning, symptoms, and future health worries. Disclosures Danilov: AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; MEI: Research Funding; Bristol-Meyers Squibb: Research Funding; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Takeda Oncology: Research Funding; Genentech: Consultancy, Research Funding; Bristol-Meyers Squibb: Research Funding; Takeda Oncology: Research Funding; Aptose Biosciences: Research Funding; Aptose Biosciences: Research Funding; Janssen: Consultancy; Pharmacyclics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Celgene: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Gilead Sciences: Consultancy, Research Funding; Bayer Oncology: Consultancy, Research Funding; Curis: Consultancy; Seattle Genetics: Consultancy; MEI: Research Funding; TG Therapeutics: Consultancy; Celgene: Consultancy; Gilead Sciences: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Abbvie: Consultancy; Abbvie: Consultancy. Yimer:AstraZeneca: Speakers Bureau; Janssen: Speakers Bureau; Seattle Genetics: Honoraria; Celgene: Honoraria; Clovis Oncology: Equity Ownership; Puma Biotechnology: Equity Ownership; Amgen: Consultancy. Boxer:Gerson Lerman: Consultancy; Best Doctors: Consultancy; Takeda: Honoraria, Speakers Bureau; AbbVie: Honoraria, Speakers Bureau. Burke:Celgene: Consultancy; Gilead: Consultancy; Roche/Genentech: Consultancy. Babu:Genentech: Research Funding. Li:Genentech: Employment; Roche: Equity Ownership. Mun:Genentech: Employment, Equity Ownership. Trask:Genentech: Employment, Equity Ownership. Masaquel:Roche: Equity Ownership; Genentech: Employment. Sharman:Acerta: Consultancy, Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding. OffLabel Disclosure: GAZYVA (obinutuzumab) is a CD20-directed cytolytic antibody and is indicated: in combination with chlorambucil, for the treatment of patients with previously untreated chronic lymphocytic leukemia; in combination with bendamustine followed by GAZYVA monotherapy, for the treatment of patients with follicular lymphoma (FL) who relapsed after, or are refractory to, a rituximab-containing regimen

Patient-reported outcomes (PRO) from the phase 2 CodeBreaK 100 trial evaluating sotorasib in KRAS p.G12C mutated non-small cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9057-9057
Author(s):  
Alexander I. Spira ◽  
Frederick Hugh Wilson ◽  
Geoffrey Shapiro ◽  
Christophe Dooms ◽  
Alessandra Curioni-Fontecedro ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Health Status ◽  
Chest Pain ◽  
Global Health ◽  
Physical Functioning ◽  
Global Health Status ◽  
Phase 2 ◽  
Cancer Symptoms ◽  
Eortc Qlq C30 ◽  
Eortc Qlq

9057 Background: In the registrational phase 2 CodeBreaK 100 trial, sotorasib demonstrated a response rate of 37.1% with median duration of 10.0 months, a median progression-free survival of 6.8 months, and a tolerable safety profile in patients with pretreated KRAS p.G12C mutated NSCLC. Patients received a median of 2 prior lines of therapy. Here, we report PRO measures of health-related quality of life (QoL), physical functioning, and key lung cancer symptoms from this trial. Methods: Eligible patients had KRAS p.G12C mutated advanced NSCLC and received prior standard therapies. Sotorasib was given at an oral daily dose of 960 mg with 21-day treatment cycles until disease progression. Disease-related symptoms and health-related QoL were evaluated as exploratory endpoints on day 1 of each cycle from baseline to discontinuation, using the European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and its lung cancer module, EORTC QLQ-LC13. The single item, 5-point scale GP5, of the Functional Assessment of Cancer Therapy-General version was used to evaluate the impact of side effects. Predefined analyses included change from baseline using descriptive statistics and mixed model for repeated measures for global health status/QoL, physical functioning, and key lung cancer symptoms of cough, dyspnea and chest pain. Results: Of 126 patients enrolled, compliance rates for each of the questionnaires were high throughout the study ( > 70%). Data up to cycle 11 (where n > 20) are presented. EORTC QLQ-C30 global health status/QoL and physical functioning were maintained over time (least-square mean changes ranged from -3.5 to 0.2 and 0.1 to 3.9, respectively). EORTC QLQ-C30 symptoms of fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, and constipation were stable or improved. Similarly, key lung cancer-related symptoms, as measured by EORTC QLQ-LC13, remained stable or improved from baseline, with the greatest least-square mean change of -11.2 (95% Cl: -16.2, -6.1) for cough, -4.9 (95% Cl: -10.3, 0.4) for chest pain, and -3.4 (95% Cl: -7.8, 1.0) for dyspnea. Most patients reported on the GP5 that they were “not at all” (54.2%-79.2%) or “a little bit” (8.3%-33.3%) bothered by side effects from sotorasib, with 0%-7.4% reporting being bothered as “quite a bit” and 0% as “very much”. Conclusions: In patients from the single-arm phase 2 trial of sotorasib, PRO measures suggested maintenance or improvement of global health status/QoL, physical functioning, and the severity of key lung cancer-related symptoms, including cough, dyspnea, and chest pain. Self-reported side effect bother was minimal. These data, together with the encouraging efficacy and safety profiles, strongly support the use of sotorasib in this population. Clinical trial information: NCT03600883.

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