TY - JOUR
T1 - Pembrolizumab for Treating Relapsed or Refractory Classical Hodgkin Lymphoma
T2 - An Evidence Review Group Perspective of a NICE Single Technology Appraisal
AU - Grimm, Sabine E.
AU - Fayter, Debra
AU - Ramaekers, Bram L. T.
AU - Petersohn, Svenja
AU - Riemsma, Rob
AU - Armstrong, Nigel
AU - Pouwels, Xavier
AU - Witlox, Willem
AU - Noake, Caro
AU - Worthy, Gillian
AU - Kleijnen, Jos
AU - Joore, Manuela A.
N1 - Funding Information:
This summary of the ERG report was compiled after NICE issued the FAD. All authors have commented on the submitted manuscript and have given their approval for the final version to be published. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of NICE or the Department of Health. Any errors are the responsibility of the authors.
Funding Information:
Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (Project Number 16/119/02). Please visit the HTA programme website for further project information (https://www.nihr.ac.uk/funding-and-support/ funding-for-research-studies/funding-programmes/health-technology assessment).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/10
Y1 - 2019/10
N2 - As part of its Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Merck Sharp & Dohme; MSD) of pembrolizumab (Keytruda (R)) to submit evidence of its clinical and cost effectiveness for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma (RRcHL) who did not respond to treatment with brentuximab vedotin. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company's submission to NICE. According to the NICE scope, pembrolizumab was compared with single or combination chemotherapy. Comparisons were undertaken in two populations: patients who did and did not receive prior autologous stem cell transplant (autoSCT; populations 1 and 2, respectively). Despite it having been recommended by NICE in population 1 at the time the ERG received the company submission, nivolumab was not included as a comparator. No studies directly comparing pembrolizumab and its comparators were identified. One ongoing, single-arm study of the efficacy and safety of pembrolizumab (KEYNOTE-087) and one comparative observational study (Cheah et al., 2016) were used to inform the comparative effectiveness of pembrolizumab and standard of care (SoC), using indirect comparisons in both populations. Almost all analyses showed significant PFS and overall response rate benefits for pembrolizumab versus SoC, but due to being based on indirect comparison, were likely to contain systematic error. The economic evaluation therefore suffered from substantial uncertainty in any estimates of cost effectiveness. Furthermore, there was a lack of evidence on the uptake and timing of allogeneic stem cell transplant, and alternative assumptions had a significant impact on cost effectiveness. Immature survival data from KEYNOTE-087 exacerbated this issue and necessitated the use of alternative data sources for longer-term extrapolation of survival. Some issues identified in the company's analyses were amended by the ERG. The revised ERG deterministic base-case incremental cost-effectiveness ratios based on the company's second Appraisal Consultation Document response for pembrolizumab versus SoC (with a commercial access agreement) for populations 1 and 2 were 54,325 pound and 62,527 pound per quality-adjusted life-year gained, respectively. There was substantial uncertainty around these ICERs, especially in population 2. NICE did not recommend pembrolizumab as an option for treating RRcHL in population 1, but recommended pembrolizumab for use within the Cancer Drugs Fund in population 2.
AB - As part of its Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Merck Sharp & Dohme; MSD) of pembrolizumab (Keytruda (R)) to submit evidence of its clinical and cost effectiveness for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma (RRcHL) who did not respond to treatment with brentuximab vedotin. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company's submission to NICE. According to the NICE scope, pembrolizumab was compared with single or combination chemotherapy. Comparisons were undertaken in two populations: patients who did and did not receive prior autologous stem cell transplant (autoSCT; populations 1 and 2, respectively). Despite it having been recommended by NICE in population 1 at the time the ERG received the company submission, nivolumab was not included as a comparator. No studies directly comparing pembrolizumab and its comparators were identified. One ongoing, single-arm study of the efficacy and safety of pembrolizumab (KEYNOTE-087) and one comparative observational study (Cheah et al., 2016) were used to inform the comparative effectiveness of pembrolizumab and standard of care (SoC), using indirect comparisons in both populations. Almost all analyses showed significant PFS and overall response rate benefits for pembrolizumab versus SoC, but due to being based on indirect comparison, were likely to contain systematic error. The economic evaluation therefore suffered from substantial uncertainty in any estimates of cost effectiveness. Furthermore, there was a lack of evidence on the uptake and timing of allogeneic stem cell transplant, and alternative assumptions had a significant impact on cost effectiveness. Immature survival data from KEYNOTE-087 exacerbated this issue and necessitated the use of alternative data sources for longer-term extrapolation of survival. Some issues identified in the company's analyses were amended by the ERG. The revised ERG deterministic base-case incremental cost-effectiveness ratios based on the company's second Appraisal Consultation Document response for pembrolizumab versus SoC (with a commercial access agreement) for populations 1 and 2 were 54,325 pound and 62,527 pound per quality-adjusted life-year gained, respectively. There was substantial uncertainty around these ICERs, especially in population 2. NICE did not recommend pembrolizumab as an option for treating RRcHL in population 1, but recommended pembrolizumab for use within the Cancer Drugs Fund in population 2.
KW - BRENTUXIMAB VEDOTIN
KW - DESIGN
KW - HEALTH
U2 - 10.1007/s40273-019-00792-7
DO - 10.1007/s40273-019-00792-7
M3 - (Systematic) Review article
SN - 1170-7690
VL - 37
SP - 1195
EP - 1207
JO - Pharmacoeconomics
JF - Pharmacoeconomics
IS - 10
ER -