886MO - Health-related quality of life (HRQoL) from KEYNOTE-204: A phase III, randomized, open-label study of pembrolizumab (pembro) vs brentuximab vedotin (BV) in relapsed or refractory classical Hodgkin lymphoma (R/R cHL)

Background

In the phase III KEYNOTE-204 (NCT02684292) study, pembro demonstrated clinically meaningful improvement in PFS vs BV in patients (pts) with R/R cHL. HRQoL was evaluated.

Methods

Pts aged ≥18 y, were post−autologous stem cell transplant (auto-SCT) or ineligible for auto-SCT, measurable disease and ECOG PS 0 or 1 were randomized 1:1 to pembro 200 mg IV Q3W or BV 1.8 mg/kg IV Q3W. EORTC QLQ-C30 and EuroQoL EQ5D scales were protocol-specified exploratory end points administered electronically at baseline (BL) and Q6W up to wk 24 and Q12W thereafter. Analysis population included pts who received ≥1 dose of study treatment and completed ≥1 HRQoL assessment. Least-squares mean (LSM) changes from BL to prespecified wk 24 end point were calculated. Time to deterioration (TTD; ≥10-point decline from BL) was assessed by Kaplan-Meier. Differences evaluated using two sided p-values not controlled for multiplicity.

Results

296 pts were included (pembro, 146; BV, 150). Completion and compliance rates were >90% for both groups at BL and remained high (>80%) at wk 24. Improvement was observed at wk 24 with pembro in the QLQ-C30 global health status/quality of life (GHS/QoL; LSM difference [95% CI]: 8.60 [3.89-13.31]; P=0.0004) and physical functioning (6.42 [1.87-10.62]; P=0.0054) scores vs BV, which showed a worsening. Similar improvements were seen for pembro in EQ5D utility (0.09 [0.04-0.14); P=0.0004) and VAS scores (6.12 [1.91-10.34]; P=0.0046). Pembro demonstrated an improvement in QLQ-C30 GHS/QoL score vs BV in pts who progressed (11.76 [5.66-17.86]; P=0.0002) and did not progress (5.10 [–2.53, 12.73]; P=0.187). Prolonged TTD was observed with pembro vs BV for QLQ-C30 GHS/QoL (HR, 0.40; 95% CI, 0.22-0.74; P=0.003) and physical functioning score (HR, 0.56; 95% CI, 0.32-0.97; P=0.034).

Conclusions

Among R/R cHL pts, pembro demonstrated improvement in HRQoL compared with BV, which showed a worsening. These data, along with statistically significant and clinically meaningful improvements in PFS, support pembro as new standard of care for pts who relapsed post auto-SCT or are ineligible for auto-SCT.

Clinical trial identification

NCT02684292.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of the ApotheCom pembrolizumab team (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

P.L. Zinzani: Advisory/Consultancy, Speaker Bureau/Expert testimony: Verastem; Advisory/Consultancy, Speaker Bureau/Expert testimony: Celltrion; Advisory/Consultancy, Speaker Bureau/Expert testimony: Gilead; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen-Cilag; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Servier; Advisory/Consultancy: Sandoz; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Immune Design; Advisory/Consultancy, Speaker Bureau/Expert testimony: Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony: Portola; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eusa Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: Kyowa Kirin; Advisory/Consultancy: Sanofi. R. Ramchandren: Advisory/Consultancy: Seattle Genetics, Sandoz-Novartis, Pharmacyclics/Janssen, Bristol-Myers Squibb; Research grant/Funding (self): Research Grant/Funding Merck, Seattle Genetics, Janssen, Genentech You. A. Santoro: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Servier; Advisory/Consultancy, Speaker Bureau/Expert testimony: Gilead Sciences; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: ArQule; Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: AbbVie; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Celgene; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Sandoz; Speaker Bureau/Expert testimony: Novartis. E. Paszkiewicz-Kozik: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Takeda; Travel/Accommodation/Expenses: Celgene. R. Gasiorowski: Honoraria (self): MSD; Honoraria (self): Takeda; Honoraria (self): Novartis; Honoraria (self): AbbVie. N.A. Johnson: Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: Merck; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): AbbVie. V. Buccheri: Advisory/Consultancy, Advisory board: AstraZeneca; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution), Travel/Accommodation/Expenses: Takeda; Travel/Accommodation/Expenses: AbbVie. G.F. Perini: Honoraria (self), Speaker Bureau/Expert testimony: Janssen; Honoraria (self): Takeda; Honoraria (self): AbbVie. M. Dickinson: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Takeda; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis. M. Ozcan: Research grant/Funding (institution): MSD; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Celgene; Honoraria (self), Research grant/Funding (institution): Roche; Research grant/Funding (institution): Janssen; Honoraria (self), Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Archigen; Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): AbbVie; Honoraria (self): Amgen; Honoraria (self): BMS. N. Sekiguchi: Research grant/Funding (institution): Ono; Research grant/Funding (institution): A2 Healthcare; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck Sharp & Dohme; Research grant/Funding (institution): Otsuka; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): PPD-SNBL,; Research grant/Funding (institution): Sumitomo Dainippon. M. Raut, Y. Zhu, A. Nahar: Full/Part-time employment: Merck & Co., Inc. P. Marinello: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc. J. Kuruvilla: Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self): Amgen; Honoraria (self): Celgene; Honoraria (self): AstraZeneca; Honoraria (self), Advisory/Consultancy: Gilead Sciences; Honoraria (self), Research grant/Funding (self): Janssen; Honoraria (self), Advisory/Consultancy: Karyopharm Therapeutics; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self): Novartis; Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Roche/Genentech. All other authors have declared no conflicts of interest.