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. 2025 May 27;10(6):105065. doi: 10.1016/j.esmoop.2025.105065

Health-related quality of life analysis of the LEAP-002 study of lenvatinib plus pembrolizumab versus lenvatinib as first-line treatment for advanced hepatocellular carcinoma

RS Finn 1,∗, M Kudo 2, P Merle 3, T Meyer 4,5, S Qin 6, M Ikeda 7, R Xu 8, J Edeline 9, B-Y Ryoo 10, Z Ren 11, A-L Cheng 12, PR Galle 13, S Kaneko 14, H Kumada 15, S Kamble 16, JM Norquist 16, K Mody 17, A Wang 16, L Dubrovsky 16, JM Llovet 18,19,20
PMCID: PMC12158521  PMID: 40435872

Abstract

Background

Patients with advanced hepatocellular carcinoma (HCC) have a substantial symptom burden that affects their health-related quality of life (HRQoL). Assessing the impact of first-line regimens on HRQoL is essential to evaluate clinical benefit in addition to efficacy and safety in this setting.

Methods

LEAP-002 is a randomized phase III trial of lenvatinib plus pembrolizumab versus lenvatinib plus placebo as first-line treatment for participants with advanced HCC. Patient-reported outcomes (PROs) were prespecified exploratory endpoints assessed in all participants randomly assigned to treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 questionnaire (EORTC QLQ-C30), EORTC QLQ Hepatocellular Carcinoma 18-item module (EORTC QLQ-HCC18), and EuroQol 5-dimension, 5-level questionnaire (EQ-5D-5L) at baseline and throughout the trial. Median time to confirmed deterioration (TTD) in PROs was estimated using the Kaplan–Meier method. Least-squares mean change from baseline to week 27 (latest time point when completion and compliance rates were ≥60% and ≥80%, respectively) in PRO scores was assessed using a constrained longitudinal data analysis model. No formal hypotheses were tested.

Results

The PRO population comprised 779 participants (lenvatinib plus pembrolizumab, n = 390; lenvatinib plus placebo, n = 389). Completion rates for all PRO assessments were >94% at baseline and >63% at week 27. Median TTD for EORTC QLQ-C30 global health status/quality-of-life score was 11.5 months [95% confidence interval (CI) 5.6 months-not reached] in the lenvatinib plus pembrolizumab group and 4.3 months (95% CI 3.5-5.5 months) in the lenvatinib plus placebo group (hazard ratio 0.80, 95% CI 0.65-0.98). TTD and least-squares mean change from baseline to week 27 were similar between treatment groups for EORTC QLQ-C30 scales, EORTC QLQ-HCC18 scores, and the EQ-5D-5L visual analog scale.

Conclusion

Adding pembrolizumab to lenvatinib, which is a current first-line option as a single agent, maintained HRQoL during the first-line treatment of participants with advanced HCC.

Key words: health-related quality of life, hepatocellular carcinoma, lenvatinib, pembrolizumab

Highlights

  • •

    First-line lenvatinib plus pembrolizumab resulted in PROs similar to lenvatinib plus placebo in patients with advanced HCC.

  • •

    TTD was numerically longer for the QLQ-C30 GHS/QoL score with lenvatinib plus pembrolizumab versus lenvatinib plus placebo.

  • •

    No notable differences between the groups were observed in other QLQ-C30 subscales or QLQ-HCC18 items.

  • •

    The proportion of participants with improved or stable HRQoL functions was similar between treatment groups.

Introduction

Patients with advanced hepatocellular carcinoma (HCC) have significant symptom burden and a poor prognosis, often in the context of underlying chronic liver disease, that considerably impact health-related quality of life (HRQoL).1,2 Although patients with advanced HCC are often ineligible for curative treatment, the development and approval of systemic first-line interventions have prolonged overall survival (OS).3, 4, 5 Therefore, treatment strategies that maintain HRQoL over time are particularly valuable, and there is increasing recognition of the importance of including HRQoL endpoints in clinical trial design as a measure of effectiveness.1,5, 6, 7

The phase III LEAP-002 study (NCT03713593) evaluated the efficacy and safety of standard-of-care lenvatinib in combination with pembrolizumab versus lenvatinib plus placebo in participants with advanced HCC. Participants treated with lenvatinib plus pembrolizumab had numerically improved progression-free survival (PFS) and OS (dual primary endpoints), objective response rate (ORR), and duration of response compared with participants who received lenvatinib plus placebo, although the prespecified significance boundaries were not met for the primary endpoints.8 At the first interim analysis (5 April 2021) and after a median follow-up of 17.6 months [interquartile range (IQR) 14.9-20.7 months], median PFS was 8.2 months with lenvatinib plus pembrolizumab versus 8.0 months with lenvatinib plus placebo [hazard ratio (HR) 0.87, 95% CI 0.73-1.02, P = 0.047, prespecified significance boundary of one-sided P = 0.002 not crossed].8 At the final analysis (21 June 2022) and after a median follow-up of 32.1 months (IQR 29.4-35.3 months), median OS was 21.2 months versus 19.0 months, respectively (HR 0.84, 95% CI 0.71-1.00, P = 0.023, superiority of boundary of one-sided P = 0.019 not crossed).8 ORR per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR) was 26.1% (95% CI 21.8% to 30.7%) with lenvatinib plus pembrolizumab versus 17.5% (95% CI 13.9% to 21.6%) with lenvatinib plus placebo.8 The incidence and severity of treatment-related adverse events (AEs) were consistent with the known safety profile reported in earlier studies3,9,10; a greater proportion of participants who received lenvatinib plus pembrolizumab versus lenvatinib plus placebo experienced treatment-related grade 3 or 4 AEs (62% versus 57%, respectively) and serious treatment-related AEs (25% versus 16%).8 The regimen remains under evaluation in the phase III LEAP-012 study in intermediate-stage HCC (NCT04246177).11,12

Patient-reported outcomes (PROs) were prespecified as exploratory endpoints in LEAP-002 to assess the impact of adding pembrolizumab to first-line lenvatinib on the HRQoL of participants with advanced HCC; these findings are reported here.

Methods

Study design

LEAP-002 is a global, multicenter, double-blind, randomized, active-controlled, phase III study of lenvatinib plus pembrolizumab versus lenvatinib plus placebo as first-line therapy for participants with advanced HCC. The study design and primary analysis of LEAP-002 have been published.8

The study was conducted in accordance with principles of Good Clinical Practice and was approved by the appropriate institutional review boards and regulatory agencies, and all participants provided written informed consent before enrollment.

Study population and randomization

Participants were eligible for enrollment if they were aged ≥18 years and had histologically, cytologically, or radiologically confirmed Barcelona Clinic Liver Cancer stage B or C HCC. Stage B disease had to be either refractory or not amenable to curative or locoregional therapy. Other eligibility criteria included one or more measurable lesions per RECIST v1.1 by BICR and no prior treatment with any systemic anticancer agents for advanced HCC. Participants with fibrolamellar or mixed hepatocellular/cholangiocarcinoma subtypes of HCC or VP4 disease were excluded.

Eligible participants were randomly assigned 1 : 1 to receive either lenvatinib plus pembrolizumab or lenvatinib plus placebo. Lenvatinib was administered by mouth once daily at a dose of 8 mg in participants who weighed <60 kg and 12 mg in participants who weighed ≥60 kg and was continued until progressive disease or unacceptable toxicity. Pembrolizumab 200 mg or placebo (normal saline) was administered intravenously every 3 weeks and continued for up to 35 cycles. Randomization was stratified by geographic region [Asia excluding Japan versus Western regions (i.e. the European Union and North America) and Japan], macroscopic portal vein invasion and/or extrahepatic spread (yes versus no), α-fetoprotein level (≤400 ng/ml versus >400 ng/ml), and Eastern Cooperative Oncology Group performance status (0 versus 1).

Study outcomes

The dual primary endpoints were PFS per RECIST v1.1 by BICR and OS, which are reported elsewhere.8 PROs were prespecified as exploratory endpoints and included mean change from baseline in HRQoL and time to confirmed deterioration (TTD; defined as the time to first onset of deterioration of ≥10 points from baseline in a given scale/subscale/item, with confirmation at the subsequent visit); these endpoints were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)13 and EORTC QLQ Hepatocellular Carcinoma 18-item module (EORTC QLQ-HCC18).14 Health utilities were also assessed using the EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L).15

Study assessments and procedures

PRO questionnaires were administered electronically at the study site on day 1 of each cycle (every 3 weeks) until week 27 and then every 6 weeks up to 1 year or the end of treatment, whichever came first. PRO questionnaires were also completed at the treatment discontinuation visit and the post-treatment safety follow-up visit (30 days after the last dose of study treatment or before the initiation of a new anticancer treatment). Administration of the questionnaires before other study procedures and assessments was strongly recommended; the EORTC QLQ-C30 was completed first, then the EORTC QLQ-HCC18, followed by the EQ-5D-5L.

Statistics

The PRO population comprised all randomly assigned participants who had one or more PRO assessments available at any time (including baseline) and received one or more doses of study treatment.

Estimates of median TTD and 95% CIs were obtained using the Kaplan–Meier method. TTD was defined as the time to first onset of a ≥10-point deterioration from baseline, with confirmation at the subsequent visit of a ≥10-point deterioration from baseline. The approach for TTD analysis assumed non-informative censoring (participants who did not have deterioration on the last day of evaluation were censored). The treatment difference in TTD between groups was assessed by stratified log-rank test, and a stratified Cox proportional hazards model with the Efron method of tie handling and a single treatment covariate was used to calculate HRs.

The time point for analysis of mean change from baseline was chosen based on blinded data review and was selected before the data cut-off for PRO assessment; this time point (week 27) was the latest that ensured a ≥60% completion rate (defined as the proportion of participants in the PRO population who completed one or more items in the questionnaire) and ≥80% compliance rate (defined as the proportion of participants who completed the PRO questionnaire among those who were expected to complete the questionnaire, excluding those missing by design). Least-squares mean (LSM) score changes from baseline to week 27 and 95% CIs were estimated using a constrained longitudinal data analysis model, with the PRO score as the response variable and treatment, time, treatment-by-time interaction, and stratification factors as covariates.

A clinically meaningful difference in EORTC QLQ-C30 scales and EORTC QLQ-HCC18 scales was defined as a change of ≥10 points from baseline.13 Overall improvement was defined as a ≥10-point improvement in score from baseline at any time during the study, with confirmation at the next visit. When the criteria for improvement were not met, overall stability was defined as a <10-point worsening in score from baseline at any time during the study, confirmed by a <10-point worsening at the next visit. Participants who did not meet the criteria for overall improvement or stability were classified as deteriorated (defined as a ≥10-point worsening in score from baseline at any time during the trial in participants without improved or stable scores). Point estimates and 95% CIs of overall improvement and overall improvement/stability rate were calculated using the Clopper–Pearson exact binomial method. Comparisons between treatment groups were made using the stratified Miettinen and Nurminen method.

Results

Between 17 January 2019 and 28 April 2020, 1309 participants were screened for enrollment in LEAP-002; 794 were eligible and randomly assigned to receive lenvatinib plus pembrolizumab (n = 395) or lenvatinib plus placebo (n = 399). Median time from randomization to data cut-off for final analysis (21 June 2022) was 32.1 months (IQR 29.4-35.3 months) in the overall intention-to-treat population.

The PRO population comprised 779 participants: 390 in the lenvatinib plus pembrolizumab group and 389 in the lenvatinib plus placebo group. Completion and compliance rates for the PRO assessment tools were >94% at baseline and similar between treatment groups (Supplementary Figure S1, available at https://doi.org/10.1016/j.esmoop.2025.105065). At week 27, completion rates for EORTC QLQ-C30 were 63.8% in the lenvatinib plus pembrolizumab group and 64.5% in the lenvatinib plus placebo group; compliance rates were 95.0% and 93.3%, respectively (Supplementary Figure S1A, available at https://doi.org/10.1016/j.esmoop.2025.105065). For EORTC QLQ-HCC18, completion rates were 64.0% in the lenvatinib plus pembrolizumab group and 64.6% in the lenvatinib plus placebo group; compliance rates were 95.0% and 92.9%, respectively (Supplementary Figure S1B, available at https://doi.org/10.1016/j.esmoop.2025.105065). For EQ-5D-5L, completion rates were 64.3% in the lenvatinib plus pembrolizumab group and 64.6% in the lenvatinib plus placebo group; compliance rates were 95.4% and 92.9%, respectively (Supplementary Figure S1C, available at https://doi.org/10.1016/j.esmoop.2025.105065).

Median TTD in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) was numerically longer in the lenvatinib plus pembrolizumab group (11.47 months, 95% CI 5.59 months-not reached) compared with the lenvatinib plus placebo group (4.34 months, 95% CI 3.45-5.52 months, HR 0.80, 95% CI 0.65-0.98) (Figure 1). TTD was similar between treatment groups for all other EORTC QLQ-C30 and QLQ-HCC18 subscales (Supplementary Figure S2A-E, available at https://doi.org/10.1016/j.esmoop.2025.105065).

Figure 1.

Figure 1

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Kaplan–Meier estimate of TTD for EORTC QLQ-C30 GHS/QoL score.

CI, confidence interval; EORTC, European Organisation for Research and Treatment of Cancer; GHS, global health status; HR, hazard ratio; NR, not reached; QLQ-C30, QoL Questionnaire Core 30; QoL, quality of life; TTD, time to confirmed deterioration.

Baseline PRO scores were balanced between treatment groups (Supplementary Table S1 and Supplementary Figure S3, available at https://doi.org/10.1016/j.esmoop.2025.105065). LSM change from baseline to week 27 for EORTC QLQ-C30 GHS/QoL score was −8.13 (95% CI −10.38 to −5.87) in the lenvatinib plus pembrolizumab group and −8.58 (95% CI −10.83 to −6.33) in the lenvatinib plus placebo group (difference 0.45, 95% CI −2.53 to 3.44) (Figure 2A; Supplementary Figure S3A, available at https://doi.org/10.1016/j.esmoop.2025.105065); similar findings were observed for other EORTC QLQ-C30 subscales (difference in LSM for physical functioning: −1.72, 95% CI −4.50 to 1.05; difference in LSM for role functioning: −0.98, 95% CI −4.88 to 2.92) (Figure 2A and B; Supplementary Figure S3B and C, available at https://doi.org/10.1016/j.esmoop.2025.105065). LSM change from baseline to week 27 for EORTC QLQ-HCC18 subscales and EQ-5D-5L visual analog scale scores were also comparable between treatment groups (Figure 2C; Supplementary Figure S3D-F and Supplementary Table S1, available at https://doi.org/10.1016/j.esmoop.2025.105065). Empirical mean change from baseline was generally stable and comparable between treatment groups for all PRO subscales (Supplementary Figure S3A-F, available at https://doi.org/10.1016/j.esmoop.2025.105065).

Figure 2.

Figure 2

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LSM change from baseline to week 27 in (A) EORTC QLQ-C30 GHS/QoL functional scales, (B) EORTC QLQ-C30 symptom scales, and (C) EORTC QLQ-HCC18 scores. CI, confidence interval; EORTC, European Organisation for Research and Treatment of Cancer; GHS, global health status; HCC, hepatocellular carcinoma; HCC18, hepatocellular carcinoma 18-item; LSM, least squares mean; QoL, quality of life; QLQ-C30, QoL Questionnaire Core 30.

A similar proportion of participants in the lenvatinib plus pembrolizumab and lenvatinib plus placebo groups experienced overall improvement in PRO scores, including EORTC QLQ-C30 GHS/QoL (18.7% versus 17.2%, respectively), EORTC QLQ-C30 role functioning (15.1% versus 13.9%), EORTC QLQ-HCC18 pain item (27.0% versus 26.1%), and EORTC QLQ-HCC18 abdominal swelling item (18.5% versus 16.0%) (Figure 3). The proportion of overall improvement, stability, and deterioration was similar between treatment groups for all other PRO assessments (Figure 3).

Figure 3.

Figure 3

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Overall rates of improvement, stability, and deterioration for EORTC QLQ-C30 scales and EORTC QLQ- HCC18 subscales. EORTC, European Organisation for Research and Treatment of Cancer; GHS, global health status; QLQ-C30, QoL Questionnaire Core 30; QLQ-HCC18, QoL Hepatocellular Carcinoma 18-item; QoL, quality of life.

Discussion

Because of the poor prognosis of advanced HCC and the significant symptom burden experienced by patients, treatment options that prolong OS while maintaining HRQoL are required.1,2,16 Although the primary analysis of the LEAP-002 study failed to meet the prespecified boundaries for superiority for the primary endpoints of PFS and OS, numerical improvements were reported at the final analysis.8 In addition, participants treated with the combination of lenvatinib plus pembrolizumab had a substantial numerical improvement in ORR, and responses were durable.8 In the current analysis, PROs were exploratory endpoints, and the addition of pembrolizumab to lenvatinib resulted in PROs similar to those with lenvatinib plus placebo in the first-line treatment of participants with advanced HCC. TTD was numerically prolonged for the EORTC QLQ-C30 GHS/QoL score with lenvatinib plus pembrolizumab versus lenvatinib plus placebo; this may be because of the number of responders treated with the lenvatinib plus pembrolizumab combination. No notable differences between the treatment groups were observed in other EORTC QLQ-C30 subscales or EORTC QLQ-HCC18 items; the proportion of participants with improved or stable HRQoL functions was similar between treatment groups.

The existing literature reporting HRQoL outcomes in patients with advanced HCC is limited. Notably, the studies that assessed PROs in patients with advanced HCC treated with the first-line combination of vascular endothelial growth factor and programmed cell death protein 1/programmed cell death ligand 1 axis inhibition also found that HRQoL was better than or similar to that with standard of care.17, 18, 19 In the global, randomized, open-label, phase III IMbrave150 trial in previously untreated patients with unresectable HCC, atezolizumab plus bevacizumab delayed deterioration of patient-reported QoL compared with sorafenib (median TTD 11.2 versus 3.6 months, respectively).17 Completion rates for EORTC QLQ-C30 and EORTC QLQ-HCC18 in the PRO-evaluable group were notably higher (≥90%) in IMbrave150 for >20 of 24 cycles compared with the current study up to week 27.18 The randomized, open-label, phase II/III ORIENT-32 trial in patients enrolled in China with unresectable hepatitis B virus-associated HCC reported a longer TTD of EORTC QLQ-C30 GHS with sintilimab plus bevacizumab biosimilar (IBI305) (6.7 months, 95% CI 5.5-7.3 months) versus sorafenib (4.1 months, 95% CI 2.9-5.2 months).19 Similarly, a delay in TTD of the EORTC QLQ-HCC18 domains was also reported with sintilimab plus bevacizumab biosimilar versus sorafenib.19 Cross-trial comparisons should be interpreted with caution, particularly because of differences in study design, inclusion criteria, and control groups. Importantly, LEAP-002 was a double-blind and placebo-controlled trial, unlike other front-line studies with immune checkpoint inhibitors.

Limitations of the current LEAP-002 HRQoL analysis include PROs being exploratory endpoints and the study not being powered to statistically compare the treatment groups. Furthermore, the number of participants completing PRO assessments decreased over time, which is a common challenge in oncology HRQoL analyses; this is particularly true from week 63 onward, and caution should be exercised when interpreting data from these later time points. Despite these limitations, the results showed that the addition of pembrolizumab to lenvatinib did not negatively affect HRQoL in participants with advanced HCC.

Conclusions

Adding pembrolizumab to lenvatinib, which is a current first-line treatment option as a single agent, delayed TTD and maintained HRQoL during first-line treatment for advanced HCC. Combined with efficacy and safety results from LEAP-002, these results support the ongoing phase III LEAP-012 study in patients with intermediate-stage HCC.

Acknowledgements

The authors thank the participants and their families and caregivers for their involvement in this trial and all investigators and site personnel. The authors also thank Corina Ductus of Eisai Inc., Nutley, NJ, USA, for her contributions to this analysis. Medical writing and/or editorial assistance was provided by Bresler Swanepoel, PhD, Holly C. Cappelli, PhD, CMPP, and Matthew Grzywacz, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

This work was supported by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme (MSD) LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (no grant number). The funders contributed to the study design, data collection, data analysis, and data interpretation, in collaboration with the authors; all authors had full access to the data. Investigators and site personnel collected data, which was housed in MSD’s database. The funders provided financial support for editorial and writing assistance. The corresponding author had full access to all the data and had final responsibility for the decision to submit for publication.

Disclosure

RF declares consulting fees (self) and grants (institution) from Eisai and Merck for the present manuscript; grants (institution) from Bayer, Bristol Myers Squibb, Eli Lilly, Novartis, Pfizer, Roche, Genentech, and Adaptimmune; consulting fees (self) from Bayer, Bristol Myers Squibb, Eli Lilly, Novartis, Pfizer, Roche, Genentech, Zai Labs, and CStone; honoraria (self) from Genentech; and payments (self) for participation on a data safety monitoring board or advisory board from AstraZeneca.

MK declares research funding to their institution and consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Chugai Pharmaceutical, and Eisai; research funding for their institution from Otsuka Pharmaceutical, Taiho Pharmaceutical, GE Healthcare Japan Corporation, and AbbVie GK; consulting fees from F. Hoffmann-La Roche, Ltd. and AstraZeneca K.K.; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Eli Lilly Japan K.K., and Takeda Pharmaceutical.

PM declares grants or contracts and consulting fees from Roche, AstraZeneca, Bayer, Ipsen, Eisai, and Merck Sharp & Dohme (MSD).

TM declares institutional grants from MSD, Boston Scientific, and Bayer and consulting fees from Signant Health, Roche, AstraZeneca, Guerbet, Geneos, Ipsen, and Grey Wolf.

MI declares consulting fees from AbbVie, AstraZeneca, Bayer, Chugai, Eisai, Eli Lilly Japan, MSD, and Ono; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbott, AstraZeneca, Bristol Myers Squibb, Chugai, Eisai, Eli Lilly Japan, MSD, and Takeda; and institutional funding from AbbVie, AstraZeneca, Bayer, Bristol Myers Squibb, Chugai, Eisai, and MSD.

JE declares consulting fees from MSD, Roche, and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, and AstraZeneca; and support for attending meeting and/or travel for attending the ESMO congress.

ZR declares consulting fees from MSD, Roche, and AstraZeneca.

A-LC declares consulting fees from AstraZeneca, Bristol Myers Squibb, Genentech/Roche, Eisai, Sanofi, MSD, Bayer, BeiGene, Ipsen Innovation, Ono Pharmaceutical, and Omega Therapeutics; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen Taiwan, Ipsen Innovation, Bayer, Sanofi, Eisai, MSD, Genentech/Roche, AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, and Omega Therapeutics; and participation on a data safety monitoring board or advisory board for Abbisko Therapeutics.

PRG declares consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, Boston Scientific, AstraZeneca, Adaptimmune, BMS, Eisai, MSD, Sirtex, Lilly, Roche, Guerbet, and Ipsen; support for attending meetings and/or travel from Bayer and Roche; and participation on a data safety monitoring board or advisory board for AstraZeneca, Roche, and Bayer.

HK declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Sumitomo Pharma, AbbVie, Eisai, and Gilead Sciences.

SK, JN, AW, and LD are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and own stock/stock options in Merck & Co., Inc.

KM is an employee of Eisai Inc., Nutley, NJ, USA.

JML declares grants or contracts from Eisai Inc, Boehringer Ingelheim, Bayer Pharmaceuticals, Bristol Myers Squibb, and Ipsen and consulting fees from Eisai, Merck, Roche, Genentech, AstraZeneca, Bayer Pharmaceuticals, Bristol Myers Squibb, Chugai, AbbVie, Eli Lilly and Company, Ipsen, Sanofi, Moderna, Glycotest, Exelixis, Sagimet, Boston Scientific, and Bluejay.

All other authors have declared no conflicts of interest.

Data Sharing

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD) is committed to providing qualified scientific researchers access to anonymized data and clinical study reports from the company’s clinical trials for the purpose of conducting legitimate scientific research. MSD is also obligated to protect the rights and privacy of trial participants and, as such, has a procedure in place for evaluating and fulfilling requests for sharing company clinical trial data with qualified external scientific researchers. The MSD data-sharing website (available at: https://externaldatasharing-msd.com/) outlines the process and requirements for submitting a data request. Applications will be promptly assessed for completeness and policy compliance. Feasible requests will be reviewed by a committee of MSD subject matter experts to assess the scientific validity of the request and the qualifications of the requestors. In line with data privacy legislation, submitters of approved requests must enter into a standard data-sharing agreement with MSD before data access is granted. Data will be made available for request after product approval in the USA and European Union or after product development is discontinued. There are circumstances that may prevent MSD from sharing requested data, including country- or region-specific regulations. If the request is declined, it will be communicated to the investigator. Access to genetic or exploratory biomarker data requires a detailed, hypothesis-driven statistical analysis plan that is collaboratively developed by the requestor and MSD subject matter experts; after approval of the statistical analysis plan and execution of a data-sharing agreement, MSD will either perform the proposed analyses and share the results with the requestor or will construct biomarker covariates and add them to a file with clinical data that are uploaded to an analysis portal so that the requestor can carry out the proposed analyses.

Supplementary data

Supplementary Table 1 and Figures 1-3
mmc1.docx (1.7MB, docx)

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Associated Data

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Supplementary Materials

Supplementary Table 1 and Figures 1-3
mmc1.docx (1.7MB, docx)

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