Aims: Health utilities summarize a patient's overall health status. This study estimated utilities based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30), a widely used measure of health-related quality-of-life (HRQoL) in oncology, using published mapping algorithms. Materials and methods: Data were from the Anaplastic Lymphoma Kinase (ALK) in Lung Cancer Trial of brigatinib (ALTA; NCT02094573), an open-label, international, phase 2 study. ALTA evaluated the efficacy and safety of two randomized dosing regimens of brigatinib in patients with locally advanced or metastatic ALK + non-small cell lung cancer (NSCLC) that had progressed on prior therapy with crizotinib. QLQ-C30 scores were mapped to European Quality-of-Life-5 Dimensions (EQ-5D) utility scores using two published algorithms (Khan et al. for EQ-5D-5L; Longworth et al. for EQ-5D-3L). The impact of brigatinib treatment on health utilities over time was assessed. Results: The analysis included 208 subjects. Mean baseline utility scores for both algorithms ranged between 0.60 - 0.71 and increased to 0.78 by cycle 5. Utility improvements were sustained during most of the treatment, before disease progression. Minor variations were observed between utility scores; Khan et al. estimates were approximately 0.01 or 0.02 points lower than Longworth et al. estimates. Limitations: Algorithms considered were limited to those available in the published literature at the time of the study. This utility analysis was exploratory, and the ALTA trial did not include an internal control group (i.e. standard of care) and was not powered to detect differences in QoL/utility outcomes between treatment arms. Conclusions: Converting QLQ-C30 scores into utilities in trials using established mapping algorithms can improve evaluation of medicines from the patient perspective. Both algorithms suggested that brigatinib improved health utility in crizotinib-refractory ALK + NSCLC patients, and improvements were maintained during most of the treatment. Clinicaltrials.gov identifier: NCT02094573.
Study Type – Diagnostic (cost effectiveness) Level of Evidence 2b What's known on the subject? and What does the study add? The Beckman Coulter prostate health index ( phi ) was developed as a combination of serum prostate specific antigen (PSA), free PSA and a PSA precursor form [−2]proPSA to calculate the probability of prostate cancer and was used as an aid in distinguishing prostate cancer from benign prostatic conditions for men with PSA test 2–10 ng/mL and non‐suspicious digital rectal examination. Phi has been shown to improve diagnostic accuracy in prostate cancer detection compared with total and free PSA. An earlier 1‐year budget impact analysis revealed it to be a complementary approach to current prostate cancer screening strategies. The current study evaluated the cost‐effectiveness of early prostate cancer detection with phi in combination with a PSA test compared with a PSA test alone from the US societal perspective. The model with over 25 annual screening cycles for men aged 50–75 years indicated that PSA plus phi dominated the PSA test alone in prostate cancer detection and consequent treatment. PSA plus phi may be an important strategy for prostate cancer detection. OBJECTIVE To evaluate the cost‐effectiveness of early prostate cancer detection with the Beckman Coulter Prostate Health Index ( phi ) (not currently available in the USA) adding to the serum prostate‐specific antigen (PSA) test compared with the PSA test alone from the US societal perspective. PATIENTS AND METHODS Phi was developed as a combination of PSA, free PSA, and a PSA precursor form [−2]proPSA to calculate the probability of prostate cancer and was used as an aid in distinguishing prostate cancer from benign prostatic conditions for men with a borderline PSA test (e.g. PSA 2–10 ng/mL or 4–10 ng/mL) and non‐suspicious digital rectal examination. We constructed a Markov model with probabilistic sensitivity analysis to estimate expected costs and utilities of prostate cancer detection and consequent treatment for the annual prostate cancer screening in the male population aged 50–75 years old. The transition probabilities, health state utilities and prostate cancer treatment costs were derived from the published literature. The diagnostic performance of phi was obtained from a multi‐centre study. Diagnostic related costs were obtained from the 2009 Medicare Fee Schedule. Cost‐effectiveness was compared between the strategies of PSA test alone and PSA plus phi under two PSA thresholds (≥2 ng/mL and ≥4 ng/mL) to recommend a prostate biopsy. RESULTS Over 25 annual screening cycles, the strategy of PSA plus phi dominated the PSA‐only strategy using both thresholds of PSA ≥2 ng/mL and PSA ≥4 ng/mL, and was estimated to save $1199 or $443, with an expected gain of 0.08 or 0.03 quality adjusted life years, respectively. The probabilities of PSA plus phi being cost effective were approximately 77–70% or 78–71% at a range of $0–$200 000 willingness to pay using PSA thresholds ≥2 ng/mL and ≥4 ng/mL, respectively. CONCLUSION The strategy PSA plus phi may be an important strategy for prostate cancer detection at both thresholds of PSA ≥2 ng/mL and PSA ≥4 ng/mL to recommend a prostate biopsy compared with using PSA alone.
This study aims to evaluate patient perceptions of subcutaneous denosumab or oral alendronate in postmenopausal women with or at risk for osteoporosis and how these perceptions influence adherence.Postmenopausal women with low bone mass were randomized to denosumab 60 mg every 6 months for 1 year (treatment period 1 [TP1]) followed by alendronate 70 mg once weekly for 1 year (treatment period 2 [TP2]), or vice versa. Beliefs about Medicines Questionnaire data were collected at baseline and at 6, 12, 18, and 24 months; a necessity-concerns differential (NCD) was calculated for each time point. Logistic regression analyses were performed to evaluate the influences of baseline characteristics on nonadherence.Participants included 250 women (alendronate/denosumab, n = 124; denosumab/alendronate, n = 126). During TP1, the NCD at month 6 was higher with denosumab than with alendronate (P = 0.0076). In TP2, the NCD was higher for women switched to denosumab than for women switched to alendronate at 6 months (P = 0.0126) and 12 months (P = 0.4605). Denosumab was preferred to alendronate regardless of treatment sequence (P < 0.0001). Covariate analysis revealed that higher TP2 baseline necessity scores were associated with lower odds of nonadherence (P = 0.0055), whereas higher concerns about medication scores were associated with higher odds of nonadherence (P = 0.0247). Higher NCD scores were also associated with lower odds of nonadherence (P = 0.0015).Participants preferred denosumab to alendronate while on treatment and had more positive perceptions of denosumab than alendronate. These perceptions were associated with better adherence.
e18032 Background: PRO enable direct measurement of the experiences of patients with cancer. Anti-programmed death 1 (PD-1) therapies have shown favorable PRO in lung cancer but a data gap remains in EC. Dostarlimab is an investigational anti-PD-1 monoclonal antibody which has shown promising activity in GARNET in advanced mismatch repair deficient (dMMR) EC pts (with an ORR of 42.9% and a disease control rate of 58.6%), and a low incidence of symptomatic grade ≥3 treatment-related adverse events (anemia [2·9%], colitis [1·9%], and diarrhea [1·9%]). Here, we report on PRO measures collected from pts with dMMR/microsattelite instability high (MSI-H) EC in the single-arm GARNET trial. Methods: Pts with dMMR/MSI-H EC confirmed by local tests, with recurrent or advanced disease that progressed on a platinum regimen were enrolled. Pts received 500 mg Q3W of dostarlimab for 4 cycles, then 1000 mg Q6W until disease progression or discontinuation. PRO assessment was an exploratory endpoint and was measured by the EORTC Quality of Life Questionnaire (QLQ-C30), a validated instrument used to evaluate quality of life, functioning, disease symptoms, and treatment-related side effects. PRO were collected at each dose administration, end of treatment, and follow-up. A mixed-model for repeated measures was used to assess change from baseline, accounting for time and baseline ECOG scores. The threshold to determine clinically meaningful group-level change was ±10 points. Results: PRO data were available for 43 pts. Compliance rates were high at 98%. Relative to baseline, pts reported meaningful improvements in pain, insomnia, and social and emotional functioning over the trial duration. Appetite, nausea, vomiting, constipation, diarrhea, and physical and role functioning were stable over the trial duration. Quality of life and global health status were also maintained. Conclusions: PRO from 43 pts enrolled in the GARNET trial show that disease- and treatment-related symptoms and quality of life are improved or maintained while receiving treatment. These data, along with with the efficacy and safety profile of dostarlimab, strongly support the use of dostarlimab in dMMR/MSI-H advanced EC. Clinical trial information: NCT02715284.
274 Background: Patient (pt) prognosis is poor following disease progression on or after primary (1L) platinum-based therapy (PBT) for advanced/recurrent (A/R) endometrial cancer (EC), and no consensus on standard second-line (2L) therapy exists. This retrospective analysis aimed to understand real-world (RW) treatment patterns of pts with A/R mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC who progressed after 1L PBT. Methods: Physicians in Cardinal Health’s Oncology Provider Extended Network submitted retrospective data by abstracting outpatient electronic medical records of pts who received systemic treatment for A/R EC following PBT from 2016 to 2018. Demographics, clinical characteristics, treatments, and outcomes were summarized descriptively. Results: This study included 84 pts with A/R dMMR/MSI-H EC (table). The majority of participating physicians were hematologists/medical oncologists (80%) and practiced in the community setting (70%). Median duration of therapy (mDOT) in 1L was 4.9 months (95% CI, 4.47–5.57); 64% of pts discontinued treatment due to completion and 35% due to disease progression. In contrast, mDOT in 2L was 6.2 months (95% CI, 5.40–6.37); 37% of pts discontinued treatment due to completion and 44% due to disease progression. The most common MMR/MSI testing modalities were next-generation sequencing (NGS) only, immunohistochemistry (IHC) only, and polymerase chain reaction (PCR) only (table). Conclusions: RW treatment patterns in pts with A/R dMMR/MSI-H EC show that most will undergo PBT retreatment. However, progression is the main reason for discontinuation during retreatment. An urgent need exists for durable therapies that improve prognosis. Opportunities to improve timely testing of MMR/MSI exist. Funding: GlaxoSmithKline, Waltham, MA, USA. [Table: see text]
9066 Background: The ALTA trial (NCT02094573), an open-label, phase 2, randomized, multicenter, international study, evaluated the efficacy and safety of BRG (arm A: 90 mg qd and arm B: 180 mg qd with 7-day lead-in at 90 mg) in patients (pts) with advanced anaplastic lymphoma kinase–positive (ALK+) NSCLC whose disease had progressed on prior therapy with crizotinib (CRZ). The objective of this analysis was to describe pt-reported outcomes (PROs) in the ALTA study. Methods: PROs were collected using the EORTC QLQ-C30 at baseline and on the first day of each cycle. Multivariable mixed effects models were constructed to estimate adjusted mean changes from baseline in QLQ-C30 scores. Cumulative distribution function (CDF) plots of EORTC QLQ-C30 change scores from baseline to Cycle 5 were generated to evaluate a clinically meaningful threshold of individual pt change, which was determined through anchor- and distribution-based methods. Results: Among 222 randomized pts, 208 (94%) completed the questionnaire at baseline and at least 1 on-treatment PRO follow-up. In multivariable analyses, there were no statistically significant differences in Global Health Status (GHS)/QOL between arms over time when adjusted for baseline score, ECOG status, and presence of liver or bone metastases. At Cycle 5, CDF plots indicated that 80% of all pts experienced an increase or no change in GHS/QOL scores; 50% of all pts experienced a clinically meaningful improvement. At Cycle 5, 80% of all pts reported a reduction or no change in pain score, and 90% of all pts reported a reduction or no change in dyspnea score. Approximately 30% of pts had clinically meaningful reductions in these symptoms. Less than 15% and < 5% of all pts reported clinically meaningful worsening of nausea/vomiting and diarrhea scores, respectively, at Cycle 5. Conclusions: Treatment with BRG for CRZ-refractory ALK+ NSCLC resulted in improved GHS/QOL scores and reduction in pain and dyspnea scores, while rates for nausea/vomiting and diarrhea were minimally worse. These pt-level benefits support BRG as a promising treatment option. Clinical trial information: NCT02094573.
PROs enable direct measurement of the experiences of pts with cancer related to an intervention. Regulators increasingly use PROs to inform the risks and benefits of new drug candidates, focusing on 3 core concepts: physical functioning (PF), disease-related symptoms (DRS), and symptomatic adverse events (AEs). Dostarlimab is an investigational anti–programmed death-1 monoclonal antibody that has shown activity in pts with advanced dMMR EC (objective response rate, 42%; disease control rate, 58%) and an acceptable safety profile. Here, we report on PROs in pts treated with dostarlimab in the single-arm GARNET trial.
Methodology
Pts with recurrent or advanced dMMR/MSI-H EC that progressed on a platinum regimen received 500 mg Q3W*4 of dostarlimab, then 1000 mg Q6W until disease progression or discontinuation (DC). PRO assessment, an exploratory endpoint, was measured using the EORTC-QLQ-C30. PROs were collected at baseline (BL), each dose cycle, and after DC. For PF and DRS (pain and fatigue), we conducted multi-item descriptive analyses, including change from BL. For symptomatic AEs and tolerability (nausea, vomiting, constipation, diarrhoea, tiredness/fatigue), we conducted item-level analyses to understand response distribution and change in response categories from BL: improved, stable, and 1-, 2-, or 3-category worsening.
Results
PRO data were available for 66/104 pts who received ≥1 dose of dostarlimab. Questionnaire compliance was consistent across domains, ranging from 100% at BL to 45% at cycle 7. Pain, fatigue, and PF were maintained above BL starting at cycles 1, 3, and 4, respectively. Symptomatic AEs were experienced by a minority of pts, with <25% and <6% of pts having 1- or ≥2-category worsening, respectively. Improved scores were reported by 6% to 37% of pts.
Conclusions
PROs from the GARNET trial showed that dostarlimab was generally well tolerated and disease-related symptoms were improved or maintained while on treatment. These data, along with the efficacy and safety profile of dostarlimab, support use of dostarlimab in pts with dMMR/MSI-H advanced EC.
Disclosures
Clinical trial registration: NCT02715284 Funding: GlaxoSmithKline, Waltham, MA, USA Encore statement: This data is presented on behalf of the original authors with their permission. Presented at European Society for Medical Oncology (ESMO) annual meeting, September 19–21, 2020, Virtual. Dr. Kristeleit reports personal fees from Tesaro. Dr. Mathews reports institutional grants from Tesaro. Dr. Redondo reports institutional research funding from PharmaMar, Roche, and Eisai; and advisory roles at PharmaMar, AstraZeneca, Tesaro, Roche, and Eisai. Dr. Brown reports honoraria from Olympus; consulting or advisory role at Caris, Tesaro, Clovis, AstraZeneca, and Genentech; and speakers' bureau at Clovis. Drs. Huang, Eliason, and Im are employees of GlaxoSmithKline.
275 Background: PRO enable direct measurement of the experiences of patients with cancer. Anti-programmed death 1 (PD-1) therapies have shown favorable PRO in lung cancer but a data gap remains in EC. Dostarlimab is an investigational anti-PD-1 monoclonal antibody which has shown promising activity in GARNET in advanced mismatch repair deficient (dMMR) EC pts and a low incidence of symptomatic grade ≥3 treatment-related adverse events. Here, we report on PRO measures collected from pts with dMMR/microsatellite instability high (MSI-H) EC in the single-arm GARNET trial. Methods: Pts with dMMR/MSI-H EC confirmed by local tests, with recurrent or advanced disease that progressed on a platinum regimen were enrolled. Pts received 500 mg Q3W of dostarlimab for 4 cycles, then 1000 mg Q6W until disease progression or discontinuation. PRO assessment was an exploratory endpoint and was measured by the EORTC Quality of Life Questionnaire (QLQ-C30), a validated instrument used evaluate quality of life (QOL), functioning, disease symptoms, and treatment-related side effects. PRO were collected at each dose administration, end of treatment, and follow-up. A mixed-model for repeated measures was used to assess change from baseline, accounting for time and baseline ECOG scores. The threshold to determine clinically meaningful group-level change was ±10 points. Results: PRO data were available for 43 pts. Compliance rates were 98%. Relative to baseline, pts reported meaningful improvements in pain, insomnia, and social and emotional functioning over the trial duration. Appetite, nausea, vomiting, constipation, diarrhea, and physical and role functioning were stable over the trial duration. QOL and global health status were also maintained. Conclusions: PRO from 43 pts enrolled in the GARNET trial show that disease- and treatment-related symptoms and QOL are improved or maintained while receiving treatment. These data, along with the efficacy and safety profile of dostarlimab, strongly support the use of dostarlimab in dMMR/MSI-H advanced EC. Funding: GlaxoSmithKline, Waltham, MA, USA. Clinical trial information: NCT02715284 .
