Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC
Introduction: In the phase 3 KEYNOTE-604 study (NCT03066778), pembrolizumab plus etoposide and platinum chemotherapy (EP) significantly (p = 0.0023) improved progression-free survival versus placebo plus EP in previously untreated extensive-stage SCLC (ES-SCLC). We present health-related quality of...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-11-01
|
| Series: | JTO Clinical and Research Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364323001157 |
| _version_ | 1797454536348008448 |
|---|---|
| author | Hye Ryun Kim, MD, PhD Mark M. Awad, MD, PhD Alejandro Navarro, MD Maya Gottfried, MD Solange Peters, MD, PhD Tibor Csőszi, MD Parneet K. Cheema, MD Delvys Rodriguez-Abreu, MD, PhD Mirjana Wollner, MD James Chih-Hsin Yang, MD, PhD Julien Mazieres, MD, PhD Francisco J. Orlandi, MD Alexander Luft, MD, PhD Mahmut Gümüş, MD Terufumi Kato, MD Gregory P. Kalemkerian, MD Yiwen Luo, PhD Melissa L. Santorelli, PhD, MPH M. Catherine Pietanza, MD Charles M. Rudin, MD, PhD |
| author_facet | Hye Ryun Kim, MD, PhD Mark M. Awad, MD, PhD Alejandro Navarro, MD Maya Gottfried, MD Solange Peters, MD, PhD Tibor Csőszi, MD Parneet K. Cheema, MD Delvys Rodriguez-Abreu, MD, PhD Mirjana Wollner, MD James Chih-Hsin Yang, MD, PhD Julien Mazieres, MD, PhD Francisco J. Orlandi, MD Alexander Luft, MD, PhD Mahmut Gümüş, MD Terufumi Kato, MD Gregory P. Kalemkerian, MD Yiwen Luo, PhD Melissa L. Santorelli, PhD, MPH M. Catherine Pietanza, MD Charles M. Rudin, MD, PhD |
| author_sort | Hye Ryun Kim, MD, PhD |
| collection | DOAJ |
| description | Introduction: In the phase 3 KEYNOTE-604 study (NCT03066778), pembrolizumab plus etoposide and platinum chemotherapy (EP) significantly (p = 0.0023) improved progression-free survival versus placebo plus EP in previously untreated extensive-stage SCLC (ES-SCLC). We present health-related quality of life (HRQoL) results from KEYNOTE-604. Methods: Patients with stage IV SCLC were randomized 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for 35 cycles plus four cycles of EP. Secondary end points included mean change from baseline to week 18 in the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire—Core 30 (QLQ-C30) global health status/quality of life (GHS/QoL) scale and time to deterioration in the composite outcome of cough, chest pain, or dyspnea from QLQ-C30 and QLQ—Lung Cancer Module 13. Two-sided, nominal p values are reported. Results: A total of 439 patients completed at least one QLQ-C30 and QLQ—Lung Cancer Module 13 assessment (pembrolizumab + EP, n = 221; placebo + EP, n = 218). GHS/QoL scores improved from baseline to week 18: least squares mean (95% confidence interval [CI]) changes were 8.7 (5.3–12.1) for pembrolizumab plus EP and 4.2 (0.9–7.5) for placebo plus EP. Between-group differences in least squares mean scores were improved for pembrolizumab plus EP (4.4 [95% CI: 0.2–8.7], p = 0.040]). Median time to deterioration for the composite end point was not reached and 8.7 (95% CI: 5.9–not reached) months, respectively (hazard ratio = 0.80 [95% CI: 0.56–1.14], p = 0.208). Conclusions: First-line pembrolizumab plus EP therapy maintained HRQoL in patients with ES-SCLC and may be associated with greater improvement than placebo plus EP. Together with the efficacy and safety findings in KEYNOTE-604, HRQoL data support the benefit of pembrolizumab in ES-SCLC. |
| first_indexed | 2024-03-09T15:38:38Z |
| format | Article |
| id | doaj.art-0e1816cce869459686df7d5b2f6d1a2d |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-03-09T15:38:38Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj.art-0e1816cce869459686df7d5b2f6d1a2d2023-11-25T04:50:21ZengElsevierJTO Clinical and Research Reports2666-36432023-11-01411100572Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLCHye Ryun Kim, MD, PhD0Mark M. Awad, MD, PhD1Alejandro Navarro, MD2Maya Gottfried, MD3Solange Peters, MD, PhD4Tibor Csőszi, MD5Parneet K. Cheema, MD6Delvys Rodriguez-Abreu, MD, PhD7Mirjana Wollner, MD8James Chih-Hsin Yang, MD, PhD9Julien Mazieres, MD, PhD10Francisco J. Orlandi, MD11Alexander Luft, MD, PhD12Mahmut Gümüş, MD13Terufumi Kato, MD14Gregory P. Kalemkerian, MD15Yiwen Luo, PhD16Melissa L. Santorelli, PhD, MPH17M. Catherine Pietanza, MD18Charles M. Rudin, MD, PhD19Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; Corresponding author. Address for correspondence: Hye Ryun Kim, MD, PhD, Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Sinchon-dong, Seodaemun-gu, Seoul 03722, South Korea.Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MassachusettsClinical Research Department, Vall d’Hebron Institute of Oncology (VHIO) and Oncology Department, Vall d'Hebron University Hospital, Barcelona, SpainOncology Department, Meir Medical Center, Kfar-Saba, IsraelOncology Department, Lausanne University Hospital, Lausanne, SwitzerlandDepartment of Oncology, Hetenyi G Korhaz Onkologiai Kozpont, Szolnok, HungaryDivision of Medical Oncology, William Osler Health System, University of Toronto, Brampton, Ontario, CanadaMedical Oncology Department, Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, SpainDepartment of Medical Oncology, Rambam Medical Center, Haifa, IsraelDepartment of Oncology, National Taiwan University Hospital and Department of Medicine, National Taiwan University Cancer Center, Taipei, TaiwanDepartment of Thoracic Oncology, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, FranceRegion Metropolitana de Santiago, Orlandi Oncologia, Santiago, ChileDepartment of Oncology No. 1 (Thoracic Surgery), Leningrad Regional Clinical Hospital, St. Petersburg, RussiaDepartment of Medical Oncology, Istanbul Medeniyet University Hospital, Istanbul, TurkeyDepartment of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, JapanDivision of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MichiganBiostatistics and Research Decision Sciences, Merck & Co., Inc., Rahway, New JerseyDivision of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Clinical Research Department, Vall d’Hebron Institute of Oncology (VHIO) and Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain; Oncology Department, Meir Medical Center, Kfar-Saba, Israel; Oncology Department, Lausanne University Hospital, Lausanne, Switzerland; Department of Oncology, Hetenyi G Korhaz Onkologiai Kozpont, Szolnok, Hungary; Division of Medical Oncology, William Osler Health System, University of Toronto, Brampton, Ontario, Canada; Medical Oncology Department, Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain; Department of Medical Oncology, Rambam Medical Center, Haifa, Israel; Department of Oncology, National Taiwan University Hospital and Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Thoracic Oncology, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France; Region Metropolitana de Santiago, Orlandi Oncologia, Santiago, Chile; Department of Oncology No. 1 (Thoracic Surgery), Leningrad Regional Clinical Hospital, St. Petersburg, Russia; Department of Medical Oncology, Istanbul Medeniyet University Hospital, Istanbul, Turkey; Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan; Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Biostatistics and Research Decision Sciences, Merck & Co., Inc., Rahway, New Jersey; Center for Observational and Real-World Evidence, Merck & Co., Inc., Rahway, New Jersey; Global Clinical Development, Merck & Co., Inc., Rahway, New Jersey; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New YorkDivision of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Clinical Research Department, Vall d’Hebron Institute of Oncology (VHIO) and Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain; Oncology Department, Meir Medical Center, Kfar-Saba, Israel; Oncology Department, Lausanne University Hospital, Lausanne, Switzerland; Department of Oncology, Hetenyi G Korhaz Onkologiai Kozpont, Szolnok, Hungary; Division of Medical Oncology, William Osler Health System, University of Toronto, Brampton, Ontario, Canada; Medical Oncology Department, Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain; Department of Medical Oncology, Rambam Medical Center, Haifa, Israel; Department of Oncology, National Taiwan University Hospital and Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Thoracic Oncology, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France; Region Metropolitana de Santiago, Orlandi Oncologia, Santiago, Chile; Department of Oncology No. 1 (Thoracic Surgery), Leningrad Regional Clinical Hospital, St. Petersburg, Russia; Department of Medical Oncology, Istanbul Medeniyet University Hospital, Istanbul, Turkey; Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan; Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Biostatistics and Research Decision Sciences, Merck & Co., Inc., Rahway, New Jersey; Center for Observational and Real-World Evidence, Merck & Co., Inc., Rahway, New Jersey; Global Clinical Development, Merck & Co., Inc., Rahway, New Jersey; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New YorkDepartment of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New YorkIntroduction: In the phase 3 KEYNOTE-604 study (NCT03066778), pembrolizumab plus etoposide and platinum chemotherapy (EP) significantly (p = 0.0023) improved progression-free survival versus placebo plus EP in previously untreated extensive-stage SCLC (ES-SCLC). We present health-related quality of life (HRQoL) results from KEYNOTE-604. Methods: Patients with stage IV SCLC were randomized 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for 35 cycles plus four cycles of EP. Secondary end points included mean change from baseline to week 18 in the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire—Core 30 (QLQ-C30) global health status/quality of life (GHS/QoL) scale and time to deterioration in the composite outcome of cough, chest pain, or dyspnea from QLQ-C30 and QLQ—Lung Cancer Module 13. Two-sided, nominal p values are reported. Results: A total of 439 patients completed at least one QLQ-C30 and QLQ—Lung Cancer Module 13 assessment (pembrolizumab + EP, n = 221; placebo + EP, n = 218). GHS/QoL scores improved from baseline to week 18: least squares mean (95% confidence interval [CI]) changes were 8.7 (5.3–12.1) for pembrolizumab plus EP and 4.2 (0.9–7.5) for placebo plus EP. Between-group differences in least squares mean scores were improved for pembrolizumab plus EP (4.4 [95% CI: 0.2–8.7], p = 0.040]). Median time to deterioration for the composite end point was not reached and 8.7 (95% CI: 5.9–not reached) months, respectively (hazard ratio = 0.80 [95% CI: 0.56–1.14], p = 0.208). Conclusions: First-line pembrolizumab plus EP therapy maintained HRQoL in patients with ES-SCLC and may be associated with greater improvement than placebo plus EP. Together with the efficacy and safety findings in KEYNOTE-604, HRQoL data support the benefit of pembrolizumab in ES-SCLC.http://www.sciencedirect.com/science/article/pii/S2666364323001157PembrolizumabChemotherapyExtensive-stage small-cell lung cancerHealth-related quality of lifePatient-reported outcomes |
| spellingShingle | Hye Ryun Kim, MD, PhD Mark M. Awad, MD, PhD Alejandro Navarro, MD Maya Gottfried, MD Solange Peters, MD, PhD Tibor Csőszi, MD Parneet K. Cheema, MD Delvys Rodriguez-Abreu, MD, PhD Mirjana Wollner, MD James Chih-Hsin Yang, MD, PhD Julien Mazieres, MD, PhD Francisco J. Orlandi, MD Alexander Luft, MD, PhD Mahmut Gümüş, MD Terufumi Kato, MD Gregory P. Kalemkerian, MD Yiwen Luo, PhD Melissa L. Santorelli, PhD, MPH M. Catherine Pietanza, MD Charles M. Rudin, MD, PhD Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC JTO Clinical and Research Reports Pembrolizumab Chemotherapy Extensive-stage small-cell lung cancer Health-related quality of life Patient-reported outcomes |
| title | Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC |
| title_full | Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC |
| title_fullStr | Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC |
| title_full_unstemmed | Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC |
| title_short | Patient-Reported Health-Related Quality of Life in KEYNOTE-604: Pembrolizumab or Placebo Added to Etoposide and Platinum as First-Line Therapy for Extensive-Stage SCLC |
| title_sort | patient reported health related quality of life in keynote 604 pembrolizumab or placebo added to etoposide and platinum as first line therapy for extensive stage sclc |
| topic | Pembrolizumab Chemotherapy Extensive-stage small-cell lung cancer Health-related quality of life Patient-reported outcomes |
| url | http://www.sciencedirect.com/science/article/pii/S2666364323001157 |
| work_keys_str_mv | AT hyeryunkimmdphd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT markmawadmdphd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT alejandronavarromd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT mayagottfriedmd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT solangepetersmdphd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT tiborcsoszimd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT parneetkcheemamd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT delvysrodriguezabreumdphd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT mirjanawollnermd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT jameschihhsinyangmdphd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT julienmazieresmdphd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT franciscojorlandimd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT alexanderluftmdphd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT mahmutgumusmd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT terufumikatomd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT gregorypkalemkerianmd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT yiwenluophd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT melissalsantorelliphdmph patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT mcatherinepietanzamd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc AT charlesmrudinmdphd patientreportedhealthrelatedqualityoflifeinkeynote604pembrolizumaborplaceboaddedtoetoposideandplatinumasfirstlinetherapyforextensivestagesclc |