Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial

Martin Reck; Michael Schenker; Ki Hyeong Lee; Mariano Provencio; Makoto Nishio; Krzysztof Lesniewski-Kmak; Randeep Sangha; Samreen Ahmed; Judith Raimbourg; Kynan Feeney; Romain Corre; Fabio Andre Franke; Eduardo Richardet; John R Penrod; Yong Yuan; Faith E Nathan; Prabhu Bhagavatheeswaran; Michael DeRosa; Fiona Taylor; Rachael Lawrance; Julie Brahmer

doi:10.1016/j.ejca.2019.05.008

Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial

Eur J Cancer. 2019 Jul:116:137-147. doi: 10.1016/j.ejca.2019.05.008. Epub 2019 Jun 11.

Authors

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

Affiliations

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.

PMID: 31195357
DOI: 10.1016/j.ejca.2019.05.008

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.

Keywords: Antineoplastic agents; Carcinoma; Ipilimumab; Lung neoplasms; Nivolumab; Non–small-cell lung cancer; Platinum-doublet chemotherapy; Quality of life; Surveys and questionnaires.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antineoplastic Agents, Immunological / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Carcinoma, Non-Small-Cell Lung / drug therapy*
Female
Health Status
Humans
Ipilimumab / administration & dosage
Lung Neoplasms / drug therapy*
Male
Middle Aged
Nivolumab / administration & dosage
Patient Reported Outcome Measures*
Quality of Life

Substances

Antineoplastic Agents, Immunological
Ipilimumab
Nivolumab

Associated data

ClinicalTrials.gov/NCT02477826