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Randomized Controlled Trial
. 2023 Jun:186:172-184.
doi: 10.1016/j.ejca.2023.03.015. Epub 2023 Mar 23.

Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice

Domenica Lorusso  1 , Nicoletta Colombo  2 , Antonio Casado Herraez  3 , Alessandro D Santin  4 , Emeline Colomba  5 , David Scott Miller  6 , Keiichi Fujiwara  7 , Sandro Pignata  8 , Sally E Baron-Hay  9 , Isabelle Laure Ray-Coquard  10 , Ronnie Shapira-Frommer  11 , Yong Man Kim  12 , Mary McCormack  13 , Rachid Massaad  14 , Allison Martin Nguyen  15 , Qi Zhao  16 , Jodi McKenzie  16 , Vimalanand S Prabhu  15 , Vicky Makker  17
Affiliations
Randomized Controlled Trial

Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice

Domenica Lorusso et al. Eur J Cancer. 2023 Jun.

Abstract

Purpose: Lenvatinib and pembrolizumab (LEN+PEMBRO) demonstrated clinically meaningful and statistically significant improvements in efficacy versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer (aEC) in the phase 3 Study 309/KEYNOTE-775. Health-related quality-of-life (HRQoL) is reported.

Patients and methods: Patients were randomly assigned to receive LEN+PEMBRO (n = 411; LEN 20 mg/day; PEMBRO 200 mg Q3W) or TPC (n = 416; doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 [weekly, 3 weeks on/1 week off]). Impact of treatment on HRQoL assessed by the global health status/quality of life (GHS/QoL) score of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) was a secondary objective; other scales of the Quality-of-Life Questionnaire (QLQ-C30), EORTC QLQ-Endometrial, 24 questions (EORTC QLQ-EN24), and EuroQoL 5 dimensions, 5 levels (EQ-5D-5L) were exploratory objectives. HRQoL was assessed on day 1 of each cycle. Completion/compliance, change from baseline, time to first and definitive deterioration were assessed. No multiplicity adjustments were applied for HRQoL endpoints.

Results: The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was week 12. HRQoL at week 12 between treatment groups was generally similar. Time to first deterioration symptom scales favoured LEN+PEMBRO for QLQ-C30 dyspnoea, and QLQ-EN24 for poor body image, tingling/numbness, and hair loss; and TPC was favoured for QLQ-C30 pain, appetite loss, and diarrhoea, and QLQ-EN24 muscular pain. While the QLQ-C30 physical functional scale favoured TPC, other functional scales were generally similar between arms. Time to definitive deterioration favoured LEN+PEMBRO on most scales.

Conclusion: HRQoL data from Study 309/KEYNOTE-775, with previously published efficacy and safety results, indicate that LEN+PEMBRO has an overall favourable benefit/risk profile versus TPC for the treatment of patients with aEC.

Clinicaltrials: GOV: NCT03517449.

Keywords: Endometrial cancer; Health-related quality of life; Lenvatinib; Patient-reported outcomes; Pembrolizumab.

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Conflict of interest statement

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Domenica Lorusso: Advisory Board: GSK, AstraZeneca, MSD, Clovis Oncology, PharmaMar, Merck Serono, Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro; Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen; Funding (inst.): MSD, Clovis Oncology, GSK, PharmaMar, AstraZeneca, Seagen, Genmab, Immogen, Incyte, Novartis, Roche; Invited Speaker: Genmab, PharmaMar, MSD; Principal Investigator: AstraZeneca, MSD, Genmab, Immunogen, Clovis, Roche, Incyte; Board of Directors: GCIG Nicoletta Colombo: Honoraria: Amgen, AstraZeneca, Clovis Oncology, Eisai, GlaxoSmithKline, Immunogen, mersana, MSD Oncology, Novartis, Pfizer, PharmaMar, Roche/Genentech, Tesaro; Consulting or Advisory Role: AstraZeneca, BioCad, Clovis Oncology, Eisai, GlaxoSmithKline, Immunogen, Mersana, MSD Oncology, Pfizer, PharmaMar, Roche/Genentech, Tesaro Antonio Casado Herraez: advisory boards for AstraZeneca, Clovis Oncology, Eisai, Merck, PharmaMar; some support for attending major international oncological conferences (virtually or face to face meetings) from PharmaMar, Lilly, Roche, AstraZeneca-Merck and GSK; Research support (institution): PharmaMar Alessandro Santin: grants from Puma, Immunomedics, Gilead, Synthon, Merck, Boehringer-Ingelheim, Genentech, Tesaro, Eisai; personal fees from Merck, Tesaro, Eisai Emeline Colomba: Honoraria: Bristol Myers Squibb, GlaxoSmithKline, Ipsen, Merck; Travel, Accommodations, Expenses: Bristol Myers Squibb, Ipsen, Pfizer David Scott Miller: Advisory Board: Eisai, Karyopharm, Tesaro, Tarveda, Myriad, GlaxoSmithKline, AbbVie, AstraZeneca, EMD Serono, Seagen; Board of Directors/Leadership Role: NRG Oncology; Research Grant: NRG Oncology, Karyopharm, Advaxis, Immunogen, Advenchen, Regeneron, Merck, Agenus, Akesobio, EMD Serono Keiichi Fujiwara: Honoraria: Chugai Pharma, Daiichi Sankyo, Eisai, Kyowa Hakko Kirin, Nippon Kayaku, Ono Pharmaceutical, Taiho Pharmaceutical, Takeda, Zeria Pharmaceutical; Consulting or Advisory Role: Abbvie, AstraZeneca, Eisai, Genmab, MSD, Pfizer, Taiho Pharmaceutical, Takeda; Research Funding (institution): AstraZeneca, Chugai Pharma, Eisai, Genmab, Immunogen, Kaken Pharmaceutical, Lilly, MSD, Oncotherapeutics, Ono Pharmaceutical, Regeneron, Shionogi, Zeria Pharmaceutical; Travel, Accommodations, Expenses: Abbvie, MSD, Pfizer; Consulting or Advisory Role - Abbvie; AstraZeneca; Eisai; Genmab; MSD; Pfizer; Taiho Pharmaceutical; Takeda; Research Funding - AstraZeneca (Inst); Chugai Pharma (Inst); Eisai (Inst); Genmab (Inst); Immunogen (Inst); Kaken Pharmaceutical (Inst); Lilly (Inst); MSD (Inst); Oncotherapeutics (Inst); Ono Pharmaceutical (Inst); Regeneron (Inst); Shionogi (Inst); Zeria Pharmaceutical (Inst); Travel, Accommodations, Expenses - Abbvie; MSD; Pfizer Sandro Pignata: Honoraria: AstraZeneca, MSD, Pfizer, PharmaMar, Roche, Tesaro; Consulting or Advisory Role: AstraZeneca, Clovis Oncology, Pfizer, PharmaMar, Roche, Tesaro; Research Funding (institution) AstraZeneca, MSD, Pfizer, Roche Sally E. Baron-Hay: Consultancy fees: Eisai, Merck Sharp and Dohme (Australia Pty Ltd), Pfizer, AstraZeneca Australia; Honoraria: Amgen, Novartis Pharmaceuticals Australia Pty Ptd, Eli Lilly Australia, Roche, Merck Sharp and Dohme (Australia Pty Ltd) Isabelle Laure Ray-Coquard: Honoraria: Abbvie, Advaxis, Amgen, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, DECIPHERA, Genmab, GlaxoSmithKline, MERSANA, MSD Oncology, OxOnc, Pfizer, PharmaMar, Roche, Tesaro; Consulting or Advisory Role: Abbvie, AstraZeneca, Bristol Myers Squibb, Clovis Oncology, Deciphera, Genmab, GlaxoSmithKline, Mersana, MSD Oncology, Pfizer, PharmaMar, Roche, Tesaro; Research Funding: BMS, MSD Oncology; Travel, Accommodations, Expenses: Advaxis, AstraZeneca, BMS, Clovis Oncology, GlaxoSmithKline, PharmaMar, Roche, Tesaro Ronnie Shapira-Frommer: Honoraria: AstraZeneca, Bristol Myers Squibb, Medison, MSD, NeoPharm, Novartis, Roche; Consulting or Advisory Role: MSD, VBL Therapeutics; Research Funding: MSD Yong Man Kim: Stock and Other Ownership Interests: Genolution, Johnson & Johnson; Research Funding: Regeneron, Roche Mary McCormack: Research Funding (institution): Roche/Genentech; Travel, Accommodations, Expenses: Roche; honoraria from GSK, AZ, and Eisai. Rachid Massaad: Full-time employee of MSD Europe Allison Martin Nguyen: Full-time employee/stock ownership: Merck & Co., Inc. Qi Zhao: Full time employee of Eisai Inc. Jodi McKenzie: Full time employee of Eisai Inc. Vimalanand S. Prabhu: Full-time employee/stock ownership: Merck & Co., Inc.; Travel, Accommodations, Expenses: Merck & Co., Inc Vicky Makker: study support (all funding to institution) / consultancy / advisory board membership from AstraZeneca, Clovis, Eisai, Faeth, Genentech, GSK, iTEOS, Karyopharm, Moreo, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Takeda, Zymeworks; Dr Makker is supported in part by the NIH/NCI Cancer Center Support Grant P30 CA008748.

Figures

Fig. 1.
Fig. 1.
HRQoL Disposition. aIncludes clinical progression and progressive disease. European Organisation for Research and Treatment of Cancer; EN24, Endometrial, 24 questions; EQ-5D-5L, EuroQoL 5 dimensions, 5 levels; HRQoL, health-related quality of life; LEN, lenvatinib; PEMBRO, pembrolizumab; QLQ-C30, Quality-of-Life Questionnaire; TPC, treatment of physician’s choice.
Fig. 2.
Fig. 2.
HRQoL Change From Baseline to Week 12 in the All-Comer Population at Week 12 (A, B) and Over Time (C-F). aPatient numbers for the sexual enjoyment functional scale and the sexual/vaginal problems symptom scales are LEN+PEMBRO: n = 65, TPC: n = 55. CI, confidence interval; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire; EORTC QLQ-EN24, EORTC QLQ-Endometrial, 24 questions; EQ-5D-5L, EuroQoL 5 dimensions, 5 levels; GHS/QoL, global health status/quality of life; HRQoL, health-related quality of life; LEN, lenvatinib; LS, least squares; PEMBRO, pembrolizumab; TPC, treatment of physician’s choice; VAS, visual analog scale.
Fig. 3.
Fig. 3.
Time to First Deterioration in the All-Comer Populationa. aDatabase cutoff: 26th October 2020. bTime to first deterioration is defined as the time from first dose of treatment to first onset of ≥10 points decrease from baseline for functional scales (decrease of ≥7 points for the for VAS 7-point threshold) and ≥10 points increase for symptom scales; a longer time to deterioration is considered more favourable. cNumber of patients in the HRQoL full analysis set with available data. dFrom product-limit (Kaplan-Meier) method for censored data. eBased on Cox regression model with treatment as a covariate stratified by MMR status, ECOG PS, geographic region, and prior history of pelvic radiation. fTwo-sided P value using Wald test (score test in case of zero event in 1 treatment group). CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire; EORTC QLQ-EN24, EORTC QLQ-Endometrial, 24 questions; EQ-5D-5L, EuroQoL 5 dimensions, 5 levels; GHS/QoL, global health status/quality of life; GI, gastrointestinal; LEN, lenvatinib; MMR, mismatch repair; NE, not estimable; NR, not reached; PEMBRO, pembrolizumab; TPC, treatment of physician’s choice; VAS, visual analog scale.
Fig. 4.
Fig. 4.
Time to First Deterioration for Selected Scales of Interest in the All-Comer Population. CI, confidence interval; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire; EORTC QLQ-EN24, EORTC QLQ-Endometrial, 24 questions; HR, hazard ratio; L, lenvatinib; P, pembrolizumab; NE, not estimable; TPC, treatment of physician’s choice.
Fig. 5.
Fig. 5.
Time to Definitive Deterioration in the All-Comer Populationa. aDatabase cutoff: 26th October 2020. bTime to definitive deterioration is defined as the time from first dose of treatment to first onset of ≥10 points decrease from baseline for functional scales (decrease of ≥7 points for the for VAS 7-point threshold) and ≥10 points increase for symptom scales from baseline without subsequent recovery or no subsequent assessment data; a longer time to deterioration is considered more favourable. cNumber of patients in the HRQoL full analysis set with available data. dFrom product-limit (Kaplan-Meier) method for censored data. eBased on Cox regression model with treatment as a covariate stratified by MMR status, ECOG PS, geographic region, and prior history of pelvic radiation. fTwosided P value using Wald test (score test in case of zero event in 1 treatment group). CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire; EORTC QLQ-EN24, EORTC QLQ-Endometrial, 24 questions; EQ-5D-5L, EuroQoL 5 dimensions, 5 levels; GHS/QoL, global health status/quality of life; GI, gastrointestinal; LEN, lenvatinib; MMR, mismatch repair; NE, not estimable; NR, not reached; PEMBRO, pembrolizumab; TPC, treatment of physician’s choice; VAS, visual analog scale.
Fig. 6.
Fig. 6.
Time to Definitive Deterioration for Selected Scales of Interest in the All-Comer Population. CI, confidence interval; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire; EORTC QLQ-EN24, EORTC QLQ-Endometrial, 24 questions; HR, hazard ratio; L, lenvatinib; NE, not estimable; P, pembrolizumab; TPC, treatment of physician’s choice.
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