国立保健医療科学院 保健医療経済評価研究センター
Center for Outcomes Research and Economic
Evaluation for Health (C2H), National Institute of
Public Health (NIPH) | URL:http://c2h.niph.go.jp

August 25, 2023

[C2H2113] Summary of cost-effectiveness evaluationof selpercatinib (RetevmoⓇ)
1. Indications
・

locally advanced or metastatic non-small cell lung cancer (NSCLC) with a RETgene fusion・

advanced or metastatic thyroid cancer (TC) with a RET gene fusion・

advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation

2. Price of the drug
Selpercatinib has been reimbursed since November 2021 at JPY 3,680 for 40 mg
and JPY 6,984.5 for 80 mg (as of August 2023). The prices are calculated basedon the similar efficacy comparison method, with a usefulness premium of 5%.
This product is designated as an H1 cost-effectiveness evaluation item.
3. Scope of cost-effectiveness evaluation
The scope of evaluation agreed upon at the first session of the Expert Committeeof Cost-Effectiveness Evaluation (ECCEE) is described below. This product is usedto treat NSCLC with a RET gene fusion, TC with a RET gene fusion, and MTC witha RET mutation. However, MTC with a RET mutation is out of the scope because
the number of patients with MTC and the proportion of the patients having MTC
with a RET mutation in the overall patients treated with selpercatinib are limited.
【NSCLC】
Population

NSCLC with a RET gene fusion【TC】
Adults with advanced or metastatic TC with a RET gene fusion

【NSCLC】
Platinum*+pemetrexed+pembrolizumabComparator*The less expensive of carboplatin and cisplatin【TC】
Lenvatinib

4. Evaluation of additional benefits【NSCLC】 The manufacturer estimated the difference in the efficacy between
selpercatinib and platinum+pemetrexed+pembrolizumab using the network
meta-analysis which utilized the results from a comparison based on thepropensity score matching between individual participant data (IPD) from
LIBRETTO-001, a single-arm trial for selpercatinib, and IPD from KEYNOTE-189,
a randomized controlled trial for pembrolizumab. The result suggested that
selpercatinib was more effective than the comparator regarding overall survival
and progression-free survival, and thereafter, the manufacturer insisted on theadditional benefits of selpercatinib over the comparator in this population. The
academic group performed the network meta-analysis using the latest data fromKEYNOTE-189 and obtained results as below table. The third ECCEE session
concluded that the results of the academic group were more appropriate. Basedon the discussion, selpercatinib has additional benefits for this population.
However, it should be noted that this conclusion is accompanied with a highuncertainty as only single-arm trial data were available for selpercatinib during
this evaluation process. An ongoing randomized controlled trial (LIBRETTO-431),
which compares selpercatinib and platinum+pemetrexed+pembrolizumab, will
provide important information for more robust evaluation.

EndpointHazard ratio [95% confidence interval](ref, comparator)

Progression-free survival

0.33 [0.16 to 0.66]

Overall survival

0.40 [0.22 to 0.71]【TC】 The manufacturer performed the naïve indirect comparison using IPD from
LIBRETTO-001, a single-arm trial for selpercatinib, and pseudo-IPD from SELECT,a randomized controlled trial for lenvatinib. The result suggested that

selpercatinib was more effective than the comparator regarding overall survival
and progression-free survival, and thereafter, the manufacturer insisted on theadditional benefits of selpercatinib over the comparator in this population. The
academic group performed the naïve indirect comparison using the latest datafrom SELECT and confirmed results similar to those by the manufacturer. The
third ECCEE session concluded that the results of the academic group were more
appropriate. Based on the discussion, selpercatinib has additional benefits for thispopulation. However, it should be noted that this conclusion is accompanied witha high uncertainty as only single-arm trial data were available for selpercatinib
during this evaluation process.
5. Results of the cost-effectiveness analysis
The manufacturer performed the cost-effectiveness analysis using the partitioned
survival model which consisted of three health statuses, “progression-freesurvival,” “survival after progression,” and “death” in both populations. The
manufacturer used the data in the evaluation of additional benefits for calculatingtransition probability. The academic group recalculated the transition probability
using the latest data in analogy with the process in the evaluation of additional
benefits. Moreover, the academic group pointed out that there were issues in thedata for quality of life and that there were several minor errors in the analysis.
The ECCEE accepted the following results.
Population
NSCLC with a RET gene fusion
Adults with advanced or metastatic TC
with a RET gene fusion

Comparator
Cisplatin+pemetrexed+pembrolizumab
Lenvatinib

ICER (JPY/QALY)
6,996,198
9,295,124