Cost–utility analysis for platinum-sensitive recurrent ovarian cancer therapy in South Korea: results of the polyethylene glycolated liposomal doxorubicin/carboplatin sequencing model
ClinicoEconomics and Outcomes Research
Cost-utility analysis for platinum-sensitive recurrent ovarian cancer therapy in South Korea: results of the polyethylene glycolated liposomal doxorubicin/carboplatin sequencing model
Hwa-Young Lee 2
Bong-Min Yang 2
Ji-Min Hong 2
Tae-Jin Lee 2
Byoung-Gie Kim 1
Jae-Weon Kim 0
Young-Tae Kim 5
Yong-Man Kim 4
Sokbom Kang 3
0 Department of Obstetrics and Gynecology, Seoul National University , Seoul , South Korea
1 Department of Obstetrics and Gynecology, Samsung Medical Center , Seoul , South Korea
2 Graduate School of Public Health, Seoul National University , Seoul , South Korea
3 Department of Obstetrics and Gynecology, National Cancer Center , Kyeonggi-do , South Korea
4 Department of Obstetrics and Gynecology, University of Ulsan , Ulsan , South Korea
5 Department of Obstetrics and Gynecology, Yonsei University , Seoul , South Korea
PowerdbyTCPDF(ww.tcpdf.org) Objective: We performed a cost-utility analysis to assess the cost-effectiveness of a chemotherapy sequence including a combination of polyethylene glycolated liposomal doxorubicin (PLD)/carboplatin versus paclitaxel/carboplatin as a second-line treatment in women with platinum-sensitive ovarian cancer. Methods: A Markov model was constructed with a 10-year time horizon. The treatment sequence consisted of first- to sixth-line chemotherapies and best supportive care (BSC) before death. Cycle length, a time interval for efficacy evaluation of chemotherapy, was 9 weeks. The model consisted of four health states: responsive, progressive, clinical remission, and death. At any given time, a patient may have remained on a current therapy or made a transition to the next therapy or death. Median time to progressions and overall survivals data were obtained through a systematic literature review and were pooled using a meta-analytical approach. If unavailable, this was elicited from an expert panel (eg, BSC). These outcomes were converted to transition probabilities using an appropriate formula. Direct costs included drug-acquisition costs for chemotherapies, premedication, adverse-event treatment and monitoring, efficacy evaluation, BSC, drug administration, and follow-up tests during remission. Indirect costs were transportation expenses. Utilities were also derived from the literature. Costs and utilities were discounted at an annual rate of 5% per cycle. Results: PLD/carboplatin combination as the second line in the sequence is more effective and costly than paclitaxel/carboplatin combination, showing an additional US$21,658 per qualityadjusted life years. This result was robust in a deterministic sensitivity analysis except when median time to progression of second-line therapies and administration cost of PLD/carboplatin per administration cycle were varied. The probability of cost-effectiveness for PLD/carboplatin combination was 49.4% at a willingness to pay $20,000. Conclusion: A PLD/carboplatin combination is an economically valuable option as second-line chemotherapy for the treatment of platinum-sensitive ovarian cancer in South Korea.
cost; utility; Markov modeling; ovarian cancer; chemotherapy
open access to scientific and medical research
Ovarian cancer is the third-commonest type of cancer of the female reproductive
system, after breast cancer and cervical cancer in Korea. It has a high mortality and a
low 5-year survival rate (around 30%).1
Epithelial ovarian cancer is often diagnosed at advanced stages or misdiagnosed
as other diseases, because patients don’t show specific symptoms until the illness
progresses to advanced stages, at which point the response
to surgery and chemotherapy is poor.2,3
The European Society of Medical Oncology4 and
Korean practice guidelines for ovarian cancer5 recommend
performing a primary optimal debulking surgery first, before
8 the start of chemotherapy. Taxane/platinum (especially
-210 carboplatin) is recommended as a first-line chemotherapy,
l-Ju with dosing frequency varying depending on the stage of the
n12 cancer. In the case of recurrence after first-line chemotherapy,
5o7 a different strategy should be applied depending on whether
.219 the recurrence occurs within 6 months since the first-line
.169 therapy. Patients who relapse within 6 months, ie,
“platinum.15 resistant” patients change to another chemotherapy option,
/yb while patients who relapse after 6 months since the
first.com line therapy, ie, “platinum-sensitive” patients, receive the
rsse platinum-based therapy once more.5,6
vep Korean practice guidelines for ovarian cancer recommend
od topotecan, gemcitabine, vinorelbine, and liposomal
.//www l.yno doxorubicin as the second-line therapy for platinum-resistant
:sp sue patients, and topotecan is used dominantly among these
tthm laon drugs. For platinum-sensitive patients who relapse after
frdedoao rrsopeF a6smthoentfhirss,t-pliancelitthaxeeral/pcya,ribsoapdlamtiinn,isttheeresdamasethcehesmecootnhde-rlaipnye
The active ingredient of polyethylene glycolated
liposomal doxorubicin (PLD) is PLD hydrochloride, which
passes through the target cell and suppresses ligation of a
nucleotide strand, DNA replication, and ultimately protein
synthesis. It results in an altered kinetic profile, extending
the half-life to 74 hours. In addition, it increases the efficacy
and decreases many of the side effects by improving the
specificity of delivery to the tumors, reducing absorption by
normal tissues, compared to doxorubicin.7
PLD can be used for both platinum-resistant and
platinum-sensitive patients.8 It was proven in a
head-tohead randomized controlled trial (RCT) that PLD was equal
in efficacy and superior in safety profile to topotecan in
platinum-resistant patients.9 In addition, PLD/carboplatin
also showed superior efficacy as the second-line therapy
in platinum-sensitive patients, extending progression-free
survival (PFS) 2 months longer than paclitaxel/carboplatin,
which was statistically significant in a head-to-head RCT
(hazard ratio 0.821, 95% confidence interval 0.72–0.94;
P = 0.005) (CALYPSO study).10
Based on the clinical trial that proved parity of clinical
efficacy of PLD with topotecan, cost-minimization analyses
for platinum-resistant patients have been performed in many
countries, such as Spain, Italy, the US, and the UK, showing
that PLD can save costs compared to topotecan.11,12 To date,
however, there has been no study that has evaluated the
cost-effectiveness of PLD for platinum-sensitive patients.
Thus, we developed a sequence model for an economic
evaluation of PLD/carboplatin as second-line therapy, in
which the treatment protocol of ovarian cancer in the real
world was reflected, and explored the long-term clinical and
economic impact of PLD/carboplatin in platinum-sensitive
recurrent ovarian cancer patients. This study is the first,
both internationally and domestically, to evaluate the
costeffectiveness of treatment sequences in women with recurrent
A Markov cohort simulation model was developed using
a Microsoft Excel spreadsheet to estimate the costs and
health outcomes in terms of life years gained (LYGs) and
quality adjusted life years (QALYs) for the full range of
relevant treatment strategies. The model consisted of four
health states, ie, response and progress to each separate line
of therapy, clinical remission, and death, so that the two
cohorts of identical patients receiving a series of six different
chemotherapies and best supportive care (BSC) could be
compared (Figure 1, Table 1). BSC means palliative therapy
without active treatment, due to treatment toxicity, patient
frailty, or lack of benefit.
There is a need to define a confoundable term beforehand.
Generally, chemotherapy for cancer treatment is administered
at intervals of 3 or 4 weeks, which is termed a “cycle.” In
the absence of unacceptable toxicity or disease progression,
patients are supposed to receive a total of six cycles of
chemotherapy and then enter the withdrawal period, which
is considered “clinical remission” in this model (Figure 1).
On the other hand, the length of time during which a patient
can move to another health state in the model is also called a
cycle in the field of modeling of economic analysis. This cycle
Respond 2nd tx
in the model can be confused with the aforementioned cycle
of chemotherapy administration. Therefore, the latter shall
be termed “Markov cycle,” while the former shall be termed
Patients are assumed to receive six lines of chemotherapy
on average after diagnosis of ovarian cancer until death,
according to an expert group composed of five clinical
gynecologists in South Korea. So the model reflected
this. Cohort A and B included the combination therapy of
PLD/carboplatin and paclitaxel/carboplatin, respectively,
as the second-line therapy in the treatment sequence. The
third- to sixth-line therapies were common to the two cohorts
Patients remained on the same therapy for six
administration cycles (18 weeks), at maximum, if they
responded to the drug. If patients did not progress or show
any serious side effects after six administration cycles, they
would enter a clinical remission state, withdrawing from the
drug. If the disease progressed during the treatment, patients
would transit to the next line of therapy. “Progress” is a
tunnel state. In other words, patients have to pass through the
“progress” state to enter the subsequent line of therapy and
cannot revert to an earlier line of therapy. Death could occur
at any point during the Markov cycle (Figure 1).
The overall clinical validity of the model was confirmed
by an expert group. Information on the chemotherapies
most commonly used from the third to the sixth line in the
treatment sequence of ovarian cancer, average median time
to progression (TTP) of BSC, overall protocols related with
drug administration, and the treatment of adverse events due
to each therapy was also obtained from them.
The length of the Markov cycle defines the period of
transition between the health states within the Markov
model and depends on the characteristics of the disease. The
length of the model cycle in this analysis was determined as
9 weeks for the following reason. Most chemotherapies are
administered at 3-week intervals (one administration cycle).
After three administration cycles, ie, 9 weeks, a series of tests
for evaluating responsiveness to chemotherapy administered
are performed, and according to the test result, it is determined
whether the patient will move to the next line of therapy or stay
on the current one. A cycle length of 9 weeks was determined
to reflect this clinical practice in the real world.
Transition probabilities to the next line of therapies and
death were drawn from the treatment-specific median TTP or
PFS and over survival (OS) data obtained from clinical trials.
The time horizon should be enough to observe the
long-term efficacy of intervention. Because the ultimate aim
of an anticancer drug is to prolong patients’ lives, the time
horizon was set as 10 years in this analysis, at which 99%
of the cohorts died.
• Patients received six lines of chemotherapy, on average,
from the diagnosis of ovarian cancer until death.
• All patients experiencing disease progression received
the next line of chemotherapy with no other treatment
options, such as radiotherapy.
• All patients experiencing disease progression on BSC
• Chemotherapies were performed on the basis of
• Cisplatin and carboplatin as a sixth-line therapy were
used on a fifty–fifty basis among patients.
• PLD/carboplatin is supposed to be administered at 4-week
intervals, while the others are administered at 3-week
intervals, according to the approved drug indication.
However, it was assumed that all chemotherapies were
administered at 3-week intervals, which is the assumption
conservative to PLD.
• If patients showed progression to the sixth line of therapy,
they would receive just BSC without any medical
treatment. Patients on BSC used mainly in-home service
and hospice service. Hospice service was used only for
the last week before death.
• The model started from the second-line therapy.
Model estimates: transition probability distributions
Transition probabilities to the next line of therapy and death
were calculated from the treatment-specific median TTP and
OS data, using the equation below.14
tp1 = 1 – (1 – tpt)1/t
tp1: yearly transition probability
tpt: the overall probability over time t
8 For this, RCTs and other experimental studies published
-210 in English and Korean from January 1990 to January 2012
l-Ju were searched using PubMed and the Cochrane database by a
2n1 systematic review. Information where several different terms
57o may be used for the same concept, such as ovarian cancer
.912 and TTP, was retrieved using Medical Subject Headings
.169 (MeSH). Systematic literature reviews were also included.
.51 After checking individual RCTs referenced in the systematic
/yb literature reviews, ones not overlapping with other RCTS in
.com our search list were included.
rsse In total, 808 papers were identified. After two reviewers
vpe independently reviewed the titles and abstracts primarily
od to identify the studies meeting the inclusion/exclusion
.//www l.yno criteria, 641 papers were excluded. Then, the full texts of
:sp sue the remaining 108 papers were reviewed, and 18 papers and
tthm laon one proceeding remained. All these procedures were
crossfrdedoao rrsopeF checked between the two reviewers.
Medial TTP and OS data obtained from the literature were
merged using a weighted average based on the sample size
(Table 2). Outcomes of the second-line chemotherapies in
the base-case analysis were extracted from only head-to-head
RCTs, even though there were other non-head-to-head trials
meeting inclusion criteria. This was because the second-line
drugs were the main target of this analysis. Outcomes of
third-line chemotherapy were extracted from two studies,15,
fourth-line from one,16 fifth-line from one,17 and sixth-line
from three.18–20 The median TTP of BSC was obtained from
opinions of clinical experts.
Model estimates: cost
Since the analysis was carried out from the societal
perspective, both nonmedical and medical costs associated
with treatments were included. However, indirect costs,
such as costs incurred by productivity loss of patient
and informal caregivers, were excluded, because not
only there are possibilities such as double-counting and
overestimation but also there is no agreed methodology
Direct medical cost includes cost associated with
drug administration (ie, cost for drug acquisition,
tests for monitoring adverse events, evaluation of
responsiveness to chemotherapy, treatment of adverse
events occurring during each chemotherapy, and service
for drug administration), BSC, and follow-up tests
during clinical remission. Cost items not reimbursed
by insurance couldn’t be identified because of a lack of
data. Therefore, the mean proportion of cost incurred by
nonreimbursement items in cancer patients was applied.
Direct nonmedical costs include round-trip transportation
costs for every ambulatory visit.
Most of the costs, except for nonreimbursement cost
and hospice service, were estimated based on microcosting.
Information concerning the proportion of cost not covered
by insurance was retrieved from the report by the National
Health Insurance Corporation (NHIC) in 2009.21 However,
this did not report ovarian cancer patient-specific data, but
rather overall cancer patients’ data. Therefore, data of the
overall cancer patients was put into the model. Hospice
service cost was from the literature.22 Since PLD has not
been listed on reimbursement yet, the price of PLD estimated
by the manufacturer was put into the base-case analysis.
Acquisition costs of other drugs were obtained from the
ceiling price paid by insurance.
Cost items and frequencies of service use were
estimated based on the current domestic and foreign clinical
practice guidelines, literature, and expert opinions. Fee of
service for drug administration, tests, and treatments of
adverse events were drawn from the Korean fee schedule.
Because the model starts from the second line, the cost of
initial diagnosis for ovarian cancer was excluded. It was
assumed that all the chemotherapies were performed on
ambulatory visits and patients experienced adverse events
only once since starting each chemotherapy treatment. The
costs for drug acquisition, administration, and treatment of
adverse event per Markov cycle (9 weeks) are presented
in Table 3.
In-home service costs include costs for paracentesis
and pain management. The costs for hospice service were
calculated as weighted average with costs by the types of
hospice facility and proportion of use. The cost for follow-up
tests during clinical remission and BSC is also presented in
All costs were converted to 2011 value and expressed
in both Korean won (￦) and US dollars. An exchange rate
of ￦1130 to $1 was applied (official exchange rate as of
Model estimates: utility
The final outcome measures used to evaluate the efficacy
in this model were LYGs and QALYs. Because there are
no QALY data of Korean ovarian cancer patients, they
were drawn from foreign literature searched by systematic
review, using PubMed CRD23 and the utility registry home
database of Tufts Medical Center in Boston.24 There was
only one study in which QALYs appropriate for health
states defined in this model were surveyed, targeting both
ovarian cancer patients and the general public.25 Although
utility values were reported by the adverse-event grades in
the literature, they could not be used, as it is impossible to
know the incidence rate of each adverse event by toxicity
grades from clinical trials. Therefore, the proportion of
grades 1–2 to 3–4 was assumed to be 50:50. Uncertainty
sur rounding this assumption was investigated in a
There is one more thing to note. This study reported two
results measured by both time trade-off (TTO) and visual
analog scale (VAS). However, the result measured by TTO
in this study was somewhat counterintuitive. It was reported
in this study that QALYs of higher-grade adverse events
were higher than those of lower-grade adverse events. This
is presumed to be a mere input error, as it is natural that the
higher the grade of adverse event, the lower the QALY figure
will be. However, it does not affect the result, because the
mean utility of grade 1–2 and 3–4 toxicity was the input in
our model. Because TTO is a more recommendable method
considering its reliability and consistency, the result measured
by TTO was used in the base-case analysis (Table 4).
The base-case analysis compares two cohorts composed
of 1000 recurrent ovarian cancer patients, each receiving
different treatment sequences, including PLD/carboplatin
(cohort A) and paclitaxel/carboplatin (cohort B) as the
In Figure 2, which shows the number of patients starting
each line of therapy, fewer patients would eventually receive
BSC in cohort A than in cohort B. This is because more patients
exited the model due to death in cohort A than in cohort B.
Table 5 summarizes the expected total costs of two cohorts
during each separate line of therapy and the difference in the
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One-way sensitivity analysis
To investigate the uncertainty, key parameters were varied in
a one-way sensitivity analysis, and results are summarized in
Table 6. Appropriate ranges of variation in parameters were
determined based on clinical and economical perspectives.
Two variables (ie, administration cost of PLD and clinical
parameters of second-line therapies) had the biggest impact
on the result. Except for these two parameters, ICERs were
in the range of ￦16,781,475 ($14,851) to ￦32,166,198
($28,466), which is within the acceptable range considering
GDP per capita in Korea.
Variation in price of PLD
There is some uncertainty surrounding the price of PLD,
because PLD has not yet been listed for reimbursement
in Korea. In the base-case analysis, the price for a 50 mg
(25 mL) pack of PLD is assumed to be ￦890,603 ($788),
which is the price suggested by the manufacturer. When the
price of PLD was varied within the range of ±5%, ICER
changed between ￦16,781,475 ($14,851) and ￦32,166,198
Variation in PLD administration cost
As mentioned before, PLD/carboplatin in the second line and
carboplatin in the sixth line are supposed to be administered
at 4-week intervals, according to the indication approved by
the Korea Food and Drug Administration, while all the other
chemotherapies are administered at 3-week intervals. However,
the model cannot reflect this difference in administration
interval. To fit our model specification, PLD/carboplatin and
carboplatin were assumed to be given at 3-week intervals
in the base-case analysis. Because carboplatin is included
commonly in both treatment sequences, assumption of 3-week
intervals of carboplatin turned out not to significantly impact
the final ICER. However, PLD/carboplatin could cause some
difference in the final result because it is a key subject of
interest in this analysis.
The assumption of administration interval of PLD/
carboplatin of 3 weeks is a very conservative one, in
that PLD cost is likely to be overestimated. In order to
adjust the potential cost overestimation, PLD/carboplatin
administration costs was varied to 3/4 and 7/8 of the cost of
4-week intervals of PLD/carboplatin, respectively, for ICER
calculation. One-way sensitivity analysis, based on these
cost variations, now showed ICER estimates less than zero
in both cases, which means that PLD/carboplatin dominates
Variation in clinical parameter
of second-line therapies
There is only one RCT that directly compared PLD/carboplatin
with paclitaxel/carboplatin as second-line therapy for
platinumsensitive recurrent ovarian cancer, and the results of this
headto-head RCT were used in the base-case analysis.11
In a sensitivity analysis, the weighted average of data
from all relevant literature comparing PLD/carboplatin or
paclitaxel/carboplatin with other comparators was put into
the model instead of the result of the head-to-head RCT. As
a result, ICER increased to ￦53,335,223 ($47,199), which
is about twice the base-case result.
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state, was performed in order to quantify the uncertainty
surrounding the parameters used in the model.
PSA is a technique for testing the robustness of the
result by investigating how cost-effectiveness changes when
multiple parameters are varied simultaneously. The 1000
results from the PSA were plotted onto a cost-effectiveness
plane (Figure 3). Most of the results of the 1000 simulations
lie on the first quadrant, which means that PLD/carboplatin
increases both QALYs and costs more than paclitaxel/
Figure 4 shows the cost-effectiveness acceptability
curve, presenting the probability that the treatment sequence
including PLD/carboplatin is cost-effective compared with
the alternative sequence for a range of maximum monetary
values that a decision-maker might be willing to pay for
1 QALY gained. We can see that PLD/carboplatin is
costeffective in nearly 49.4% of samples at a willingness to pay
:sp sue in treatment of all types of cancers was applied, which was
tthm lona drawn from the report by the NHIC, since there were no
dedoa ropeF ovarian cancer-specific data available.
When the nonreimbursement proportion of overall
services (ie, ambulatory care and hospitalization) was applied
in the sensitivity analysis, ICER increased to ￦28,380,301
($25,115). In addition, when it was assumed that all cost items
were covered by insurance, ICER decreased to ￦20,862,761
Probabilistic sensitivity analysis
Probabilistic sensitivity analysis (PSA), involving 1000
random simulations of median TTPs of each chemotherapy,
cost of hospice service, and utilities according to each health
a threshold of $20,000, which is close to the GDP per capita
The CALYPSO study comparing PLD/carboplatin directly
with paclitaxel/carboplatin as second-line therapy in
platinum-sensitive recurrent ovarian cancer patients showed
superiority in PFS and a better therapeutic index of PLD/
carboplatin over a standard paclitaxel/carboplatin regimen.1
However, value for money of PLD/carboplatin in
platinumsensitive patients has not yet been proven.
The main objective of this analysis was to estimate the
long-term clinical impact and cost-effectiveness of PLD/
carboplatin in platinum-sensitive recurrent ovarian cancer in
Korea. Efficacy such as PFS or OS might be important factors
for decisions concerning drug selection for cancer patients in
the clinical setting. However, straight comparison of efficacy
outcomes can be misleading, because quality of life can be
more valuable to cancer patients than mere extension of life.
Some drugs have low tolerance, low compliance, or more
adverse effects while prolonging PFS or OS, but efficacy
measures can’t capture these aspects. Utility can combine
this efficacy and quality of life into a single measure.26
Accordingly, a cost–utility analysis was applied in this
analysis to this end.
Analysis was performed through decision-modeling
because the treatment sequences after second-line therapies
in the trial were not presented clearly and were different
between the two arms. The treatment-sequence model of
ovarian cancer patients, including PLD/carboplatin and
paclitaxel/carboplatin as a second line, was constructed
to reflect clinical protocol for patients receiving series of
chemotherapies, depending on responsiveness to drugs.
PLD is a kind of improved formulation of conventional
doxorubicin and surrounded by fatty coating called liposome,
which enables doxorubicin to remain longer inside the body.
This means that more of the doxorubicin can be delivered
to the target cancer cell, while having fewer side effects
on healthy tissue. In fact, PLD/carboplatin can be used for
metastatic breast cancer, Kaposi’s sarcoma, and ovarian
The average median OS estimated by the model was 29.15
and 29.26 months in the PLD/carboplatin and paclitaxel/
carboplatin arms, respectively. There was about a 3-month
gap between OS of paclitaxel/carboplatin in the RCT and the
one estimated by modeling, while OS of PLD/carboplatin
in the RCT was similar to the one estimated by modeling.
The reason for this is that OS in the RCT was not entirely due
to the effect of PLD/carboplatin and paclitaxel/carboplatin,
because the types of treatments after second-line therapy in
the RCT were not controlled identically in both arms.
Predicted ICER under the base-case assumption was
￦24,473,836 ($21,658) per QALY. It was not considered
that there was a need to perform additional subgroup analysis,
because the target of the base-case analysis, ie,
platinumsensitive recurrent ovarian cancer patients, was already
narrowed down. One-way sensitivity analysis showed that
when key parameters were varied, ICERs (QALYs) lay in the
range of ￦16,781,475 ($14,851) to ￦32,166,198 ($28,466),
except when administration cost of PLD/carboplatin and
source of clinical parameters of second-line therapies were
varied. Probability sensitivity analysis revealed that there
is sufficient uncertainty surrounding the baseline ICER.
The cost-effectiveness acceptability curve demonstrated
that there is about 49.4% probability of cost-effectiveness
in the treatment sequence including PLD/carboplatin when
decision-makers have the willingness to pay the threshold of
$20,000, which was the GDP per capita of Korea in 2010.
When considering clinical superiority, cost-effectiveness
of PLD, and current limited therapeutic options in
platinumsensitive recurrent ovarian cancer, overall, PLD/carboplatin can
be said to be a valuable treatment option in these patients.
Although this economic analysis was performed according
to the current methodological guidelines recommended,
there are a few caveats. Firstly, although the administration
cycle of PLD/carboplatin and carboplatin is 4 weeks, it
was assumed to be 3 weeks because other chemotherapies,
except for PLD/carboplatin and carboplatin, are administered
every 3 weeks, and the model cannot reflect this difference
in the administration interval. ICER was very sensitive to
the variation of administration cost of PLD/carboplatin.
However, we can guess that this is a conservative assumption
for PLD/carboplatin, because the cost of PLD/carboplatin
was put into the model more frequently than it should have
been under this assumption. PLD/carboplatin would become
even more cost-effective if the administration cycle of PLD/
carboplatin could be reflected precisely.
Secondly, indirect costs incurred by patients and informal
caregivers, such as cost of productivity loss, were not
included. Incorporation of these societal costs would further
decrease ICER to an even lower level.
Finally, we used OS data of the CALYPSO study,
repor ted in proceedings because it has not been
published yet. In addition, chemotherapies administered
after PLD/carboplatin and paclitaxel/carboplatin until death
were not controlled identically between the two groups in the
trial, because it was not OS but median TTP which was the
main key outcome. Therefore, it cannot be said that the OS
result was entirely due to the effect of PLD/carboplatin and
paclitaxel/carboplatin. Nevertheless, OS in the CALYPSO
study was used, because there were no other data that were
In conclusion, PLD/carboplatin as a second therapeutic
option in patients with platinum-sensitive recurrent ovarian
cancer is cost-effective compared to the standard paclitaxel/
carboplatin regimen, based on clinical and economical
perspectives. These data can provide an objective basis for
local decision-making on the possible economic impact of
use of this intervention if different variables between the
countries can be incorporated accordingly.
This research was funded by Janssen Korea. The authors
have no direct or indirect financial relationship with the
.//www l.yno sponsor. The manuscript was prepared without a contract or
:sp sue funding from the sponsor. Publication of study results was
tthm laon not contingent on the sponsor’s approval.
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