Patient-Reported Outcomes in Oncology Clinical Trials: Stakeholder Perspectives from the Accelerating Anticancer Agent Development and Validation Workshop 2019

Bhatnagar, Vishal; Hudgens, Stacie; Piault-Louis, Elisabeth; Jones, Lee W.; Beaver, Julia A.; Lyerly, H. Kim; Reaman, Gregory H.; Fleming, Thomas R.; Kluetz, Paul G.

doi:10.1634/theoncologist.2020-0062

Cited by 9 publications

(7 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The incorporation of PRO measures is also a strength of the study, and we anticipate that additional analyses will provide valuable information for future study designs, including those focusing on the area of survivorship in patients with advanced breast cancer. 23 In conclusion, the combination of entinostat and exemestane did not improve outcomes in patients with advanced endocrine-resistant breast cancer. It remains to be confirmed if there is a role for HDAC inhibitors in a biomarkerselected population or in other breast cancer settings on the basis of results from ongoing correlative analysis and other clinical trials.…”

Section: Discussionmentioning

confidence: 84%

See 1 more Smart Citation

E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor–Positive Advanced Breast Cancer. A Trial of the ECOG-ACRIN Cancer Research Group

Connolly

Zhao

Miller

et al. 2021

JCO

View full text Add to dashboard Cite

PURPOSE Endocrine therapy resistance in advanced breast cancer remains a significant clinical problem that may be overcome with the use of histone deacetylase inhibitors such as entinostat. The ENCORE301 phase II study reported improvement in progression-free survival (PFS) and overall survival (OS) with the addition of entinostat to the steroidal aromatase inhibitor (AI) exemestane in advanced hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer. PATIENTS AND METHODS E2112 is a multicenter, randomized, double-blind, placebo-controlled phase III study that enrolled men or women with advanced HR-positive, HER2-negative breast cancer whose disease progressed after nonsteroidal AI. Participants were randomly assigned to exemestane 25 mg by mouth once daily and entinostat (EE) or placebo (EP) 5 mg by mouth once weekly. Primary end points were PFS by central review and OS. Secondary end points included safety, objective response rate, and lysine acetylation change in peripheral blood mononuclear cells between baseline and cycle 1 day 15. RESULTS Six hundred eight patients were randomly assigned during March 2014-October 2018. Median age was 63 years (range 29-91), 60% had visceral disease, and 84% had progressed after nonsteroidal AI in metastatic setting. Previous treatments included chemotherapy (60%), fulvestrant (30%), and cyclin-dependent kinase inhibitor (35%). Most common grade 3 and 4 adverse events in the EE arm included neutropenia (20%), hypophosphatemia (14%), anemia (8%), leukopenia (6%), fatigue (4%), diarrhea (4%), and thrombocytopenia (3%). Median PFS was 3.3 months (EE) versus 3.1 months (EP; hazard ratio = 0.87; 95% CI, 0.67 to 1.13; P = .30). Median OS was 23.4 months (EE) versus 21.7 months (EP; hazard ratio = 0.99; 95% CI, 0.82 to 1.21; P = .94). Objective response rate was 5.8% (EE) and 5.6% (EP). Pharmacodynamic analysis confirmed target inhibition in entinostat-treated patients. CONCLUSION The combination of exemestane and entinostat did not improve survival in AI-resistant advanced HR-positive, HER2-negative breast cancer.

show abstract

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor–Positive Advanced Breast Cancer. A Trial of the ECOG-ACRIN Cancer Research Group

Connolly

Zhao

Miller

et al. 2021

JCO

View full text Add to dashboard Cite

show abstract

“…Furthermore, the patient's perspective on their own health is becoming increasingly important in clinical trials. Trial sponsors that understand the patient, their condition, and the burden of participation could improve recruitment, retention, and the value of data generated by clinical trials [ [73] , [74] , [75] ]. A successful patient-focused approach would mean that treatments and clinical trials would address aspects of disease that are most important to patients leading to a better understanding of the scope over which a disease can impact a patient's life.…”

Section: Discussionmentioning

confidence: 99%

Bridging the gap between statistical significance and clinical relevance: A systematic review of minimum clinically important difference (MCID) thresholds of scales reported in movement disorders research

Mishra,

Sudheer,

Rajan

et al. 2024

Heliyon

View full text Add to dashboard Cite

“…Designing clinical trials with a focus on a core set of clinical outcomes that are meaningful to patients is viewed as a priority by researchers, regulators, payers, and policymakers [ 1 , 2 ]. The current period of rapid progress in drug development has led to the introduction of novel therapies and combinations of multiple drug classes that are characterized by diverse toxicities and adverse events.…”

Section: Introductionmentioning

confidence: 99%

Using qualitative interviews to identify patient-reported clinical trial endpoints and analyses that are the most meaningful to patients with advanced breast cancer

et al. 2023

View full text Add to dashboard Cite

Background Designing clinical trials with the emphasis on the patient-centered approach and focusing on clinical outcomes that are meaningful to patients is viewed as a priority by drug developers, regulatory agencies, payers, clinicians, and patients. This study aimed to capture information on clinical trial endpoints that would be most important and relevant for patients with advanced breast cancer, based on patient-reported outcomes. Methods Patients with either advanced triple-negative breast cancer [TNBC] and a maximum of two lines of systemic therapy or hormone receptor-positive/human epidermal growth factor receptor 2-negative [HR+/HER2−] breast cancer and a maximum of three lines of systemic therapy, participated in semi-structured concept elicitation interviews. Concept saturation was assessed. A sign, symptom, or impact was defined as “salient” if mentioned by ≥ 60% of participants, with an average bother rating of ≥ 5 (0–10 Scale). Participants were also asked about treatment priorities and to evaluate hypothetical scenarios showing different health-related functioning and quality-of-life treatment outcomes, using graphical representations. Results Thirty-two participants (97% women; aged 29+ years) with TNBC (n = 17) or HR+/HER2− breast cancer (n = 15) provided generally similar reports on symptom experience, with fatigue and pain being most salient, though importance of certain treatment-related symptoms varied between the two groups. Patients reported consistent perspectives on the importance of treatment outcomes: when considering a new treatment, they prioritized efficacy of the therapy, acceptable tolerability, stability, predictability of symptoms over time, and the duration of preserved health-related quality of life and physical functioning. The meaningful difference in preserved physical functioning was 2–3 months for 46% of participants with TNBC, whereas for most participants with HR+/HER2− breast cancer it started from 6–7 months. Both groups of participants found it easier to accept some toxicity at the beginning of therapy if it was followed by improvement, as opposed to improvement followed by deterioration. Conclusion The results may help to inform the design of patient-centered clinical trials, to interpret health-related quality of life and/or patient-reported outcomes, and to optimize care for patients with advanced breast cancer.

show abstract

Patient-Reported Outcomes in Oncology Clinical Trials: Stakeholder Perspectives from the Accelerating Anticancer Agent Development and Validation Workshop 2019

Abstract: The measurement and analysis of patient-reported outcomes is important in cancer clinical trials. This commentary reports advances and challenges from presentations at the 2019 Accelerating Anticancer Agent Development and Validation (AAADV) Workshop Patient-Reported Outcomes Session.

Cited by 9 publications

References 5 publications

E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor–Positive Advanced Breast Cancer. A Trial of the ECOG-ACRIN Cancer Research Group

E2112: Randomized Phase III Trial of Endocrine Therapy Plus Entinostat or Placebo in Hormone Receptor–Positive Advanced Breast Cancer. A Trial of the ECOG-ACRIN Cancer Research Group

Bridging the gap between statistical significance and clinical relevance: A systematic review of minimum clinically important difference (MCID) thresholds of scales reported in movement disorders research

Using qualitative interviews to identify patient-reported clinical trial endpoints and analyses that are the most meaningful to patients with advanced breast cancer

Contact Info

Product

Resources

About