Martin Reck1, Michael Schenker2, Ki Hyeong Lee3, Mariano Provencio4, Makoto Nishio5, Krzysztof Lesniewski-Kmak6, Randeep Sangha7, Samreen Ahmed8, Judith Raimbourg9, Kynan Feeney10, Romain Corre11, Fabio Andre Franke12, Eduardo Richardet13, John R Penrod14, Yong Yuan15, Faith E Nathan16, Prabhu Bhagavatheeswaran17, Michael DeRosa18, Fiona Taylor19, Rachael Lawrance20, Julie Brahmer21. 1. LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Wöhrendamm 80, 22927 Grosshansdorf, Germany. Electronic address: m.reck@lungenclinic.de. 2. Centrul de Oncologie Sf Nectarie, 23A Caracal St, Craiova, 200347, Romania. Electronic address: mike_schenker@yahoo.com. 3. Chungbuk National University Hospital, 776, 1 Sunhwan-ro, Seowon-gu, Cheongju-si, Chungcheonbuk-do, 28644, South Korea. Electronic address: kihlee@chungbuk.ac.kr. 4. Universidad Autónoma de Madrid, Instituto de Investigación Puerta de Hierro, Hospital Puerta de Hierro de Majadahonda, C / Manuel de Falla 1, Madrid, Majadahonda, 28222, Spain. Electronic address: mprovenciop@gmail.com. 5. The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Tokyo, Koto-ku, 135-8550, Japan. Electronic address: mnishio@jfcr.or.jp. 6. Oddzial Onkologii Radioterapii Szpital/Gdansk Medical University, UI. Powstania Styczniowego 1, Gdynia, 81-519, Poland. Electronic address: krzychu03@hotmail.com. 7. Cross Cancer Institute, 11560 University Ave, Edmonton, Alberta, T6G 1Z2, Canada. Electronic address: randeep.sangha@albertahealthservices.ca. 8. University Hospitals of Leicester NHS Trust, Department of Infection, Leicester, Leicestershire, LE1 5WW, UK. Electronic address: samreen.ahmed@uhl-tr.nhs.uk. 9. Institut de Cancérologie de l'Ouest, Centre Rene Gauducheau, Boulevard Jacques Monod, 44805 Nantes-Saint Herblain Cedex, France. Electronic address: judith.raimbourg@ico.unicancer.fr. 10. Notre Dame University and Edith Cowan University, 100 Murdoch Drive, Murdoch, Perth, Western Australia, 6150, Australia. Electronic address: kynan@oncowest.com.au. 11. CHU de Rennes, 2 Rue Henri le Guilloux, Rennes, 35033, France. Electronic address: romain.corre@chu-rennes.fr. 12. CACON, Hospital de Caridade de Ijuí, Av David Jose Martins, Centro, Ijuí, Rio Grande do Sul, 98700-000, Brazil. Electronic address: ff.oncosite@gmail.com. 13. IONC - Universidad Católica de Córdoba, Parana 560. 2 Piso, Cordoba, 5000, Argentina. Electronic address: eduardorichardet@gmail.com. 14. Bristol-Myers Squibb, 3401 Princeton Pike, Lawrenceville, NJ, 08648, USA. Electronic address: john.penrod@bms.com. 15. Bristol-Myers Squibb, 3401 Princeton Pike, Lawrenceville, NJ, 08648, USA. Electronic address: yong.yuan@bms.com. 16. Bristol-Myers Squibb, 3401 Princeton Pike, Lawrenceville, NJ, 08648, USA. Electronic address: faith.nathan@bms.com. 17. Bristol-Myers Squibb, 3401 Princeton Pike, Lawrenceville, NJ, 08648, USA. Electronic address: prabhu.bhagavatheeswaran@bms.com. 18. Adelphi Values, 290 Congress Street 7th Floor, Boston, MA, 02210, USA. Electronic address: michael.derosa@adelphivalues.com. 19. Adelphi Values, 290 Congress Street 7th Floor, Boston, MA, 02210, USA. Electronic address: fiona.taylor@adelphivalues.com. 20. Adelphi Values, Adelphi Mill, Grimshaw Ln, Bollington, Cheshire, SK10 5JB, UK. Electronic address: rachael.lawrance@adelphivalues.com. 21. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans St, CRB1-G94, Baltimore, MD, 21287, USA. Electronic address: brahmju@jhmi.edu.
Abstract
BACKGROUND: In the phase III CheckMate 227 study, first-line nivolumab + ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; ≥10 mutations/megabase). AIM: To evaluate patient-reported outcomes (PROs) in this population. METHODS: Disease-related symptoms and general health status were assessed using the validated PRO questionnaires Lung Cancer Symptom Scale (LCSS) and EQ-5D, respectively. LCSS average symptom burden index (ASBI) and three-item global index (3-IGI) and EQ-5D visual analogue scale (VAS) and utility index (UI) scores and changes from baseline were analysed descriptively. Longitudinal changes were assessed by mixed-effect model repeated measures (MMRMs) and time to first deterioration/improvement analyses. RESULTS: In the high TMB population, PRO questionnaire completion rates were ∼90% at baseline and >80% for most on-treatment assessments. During treatment, mean changes from baseline with nivolumab + ipilimumab showed early, clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; with chemotherapy, symptoms and health-related quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following induction (EQ-5D VAS). MMRM-assessed changes in symptom burden were improved with nivolumab + ipilimumab versus chemotherapy. Symptom deterioration by week 12 was lower with nivolumab + ipilimumab versus chemotherapy (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% confidence interval 2.4-22.5]), irrespective of discontinuation. Time to first deterioration was delayed with nivolumab + ipilimumab versus chemotherapy across LCSS and EQ-5D summary measures. CONCLUSION: First-line nivolumab + ipilimumab demonstrated early, sustained improvements in PROs versus chemotherapy in patients with advanced NSCLC and high TMB. CLINICAL TRIAL REGISTRATION: NCT02477826.
RCT Entities:
BACKGROUND: In the phase III CheckMate 227 study, first-line nivolumab + ipilimumab significantly prolonged progression-free survival (co-primary end-point) versus chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and high tumour mutational burden (TMB; ≥10 mutations/megabase). AIM: To evaluate patient-reported outcomes (PROs) in this population. METHODS: Disease-related symptoms and general health status were assessed using the validated PRO questionnaires Lung Cancer Symptom Scale (LCSS) and EQ-5D, respectively. LCSS average symptom burden index (ASBI) and three-item global index (3-IGI) and EQ-5D visual analogue scale (VAS) and utility index (UI) scores and changes from baseline were analysed descriptively. Longitudinal changes were assessed by mixed-effect model repeated measures (MMRMs) and time to first deterioration/improvement analyses. RESULTS: In the high TMB population, PRO questionnaire completion rates were ∼90% at baseline and >80% for most on-treatment assessments. During treatment, mean changes from baseline with nivolumab + ipilimumab showed early, clinically meaningful improvements in LCSS ASBI/3-IGI and EQ-5D VAS/UI; with chemotherapy, symptoms and health-related quality of life remained stable (LCSS ASBI/3-IGI, EQ-5D UI) or improved following induction (EQ-5D VAS). MMRM-assessed changes in symptom burden were improved with nivolumab + ipilimumab versus chemotherapy. Symptom deterioration by week 12 was lower with nivolumab + ipilimumab versus chemotherapy (22.3% versus 35.0%; absolute risk reduction: 12.7% [95% confidence interval 2.4-22.5]), irrespective of discontinuation. Time to first deterioration was delayed with nivolumab + ipilimumab versus chemotherapy across LCSS and EQ-5D summary measures. CONCLUSION: First-line nivolumab + ipilimumab demonstrated early, sustained improvements in PROs versus chemotherapy in patients with advanced NSCLC and high TMB. CLINICAL TRIAL REGISTRATION: NCT02477826.