Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331

Antineoplastic Combined Chemotherapy Protocols Humans Lung Neoplasms / drug therapy Neoplasm Recurrence, Local / drug therapy Nivolumab / adverse effects Progression-Free Survival Small Cell Lung Carcinoma / drug therapy
PD-1 biomarkers immunotherapy small-cell lung cancer

Journal

Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735

Informations de publication

Date de publication:
05 2021
Historique:
received: 31 07 2020
revised: 13 01 2021
accepted: 17 01 2021
pubmed: 5 2 2021
medline: 22 4 2021
entrez: 4 2 2021
Statut: ppublish

Résumé

Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC. CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS). Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%. Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.

Sections du résumé

BACKGROUND
Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC.
PATIENTS AND METHODS
CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS).
RESULTS
Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%.
CONCLUSION
Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.

Identifiants

DOI: 10.1016/j.annonc.2021.01.071 PMID: 33539946
pubmed: 33539946
pii: S0923-7534(21)00099-5
doi: 10.1016/j.annonc.2021.01.071
pii:
doi:

Substances chimiques

Nivolumab 31YO63LBSN

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

631-641

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure DRS: consulting or advisory role: Aptitude Health (Inst), AstraZeneca (Inst), Bayer (Inst), Bristol Myers Squibb (Inst), Celgene (Inst), Dracen Pharmaceuticals (Inst), EMD Serono (Inst), Evelo Biosciences (Inst), Genentech/Roche (Inst), GlaxoSmithKline (Inst), Iksuda Therapeutics (Inst), Illumina (Inst), Merck (Inst), Molecular Templates (Inst), Nektar Therapeutics (Inst), Novartis (Inst), Pfizer (Inst), PharmaMar (Inst), Roche (Inst), Seattle Genetics (Inst), Takeda (Inst), TRIPTYCH Health Partners (Inst), TRM Oncology, Williams and Connolly LLP (Inst); research funding: Aeglea BioTherapeutics (Inst), Astellas (Inst), AstraZeneca (Inst), BIND Therapeutics (Inst), Bristol Myers Squibb (Inst), Celgene (Inst), Celldex (Inst), Clovis (Inst), Daiichi Sankyo (Inst), Eisai (Inst), Eli Lilly (Inst), EMD Serono (Inst), G1 Therapeutics (Inst), Genentech (Inst), GRAIL (Inst), ImClone Systems (Inst), ImmunoGen (Inst), Ipsen (Inst), Janssen (Inst), MedImmune (Inst), Merck (Inst), Molecular Partners (Inst), Nektar (Inst), Neon (Inst), Novartis (Inst), Takeda (Inst), Transgene (Inst), University of Texas Southwestern (Inst); travel, accommodations, expenses: Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Bristol Myers Squibb, Genentech/Roche, GlaxoSmithKline, Janssen, Merck, Novartis, Seattle Genetics, Spectrum Pharmaceuticals, and Takeda. DV: honoraria: AstraZeneca; consulting or advisory role: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche; travel, accommodations, expenses: AstraZeneca. TEC: consulting or advisory role: A&D Pharma, Amgen, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Genentech/Roche, Janssen, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Servier; travel, accommodations, expenses: A&D Pharma, Amgen, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Ipsen, Janssen, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, Servier. SG: consulting or advisory role: Bristol Myers Squibb, Nektar; research funding: Bristol Myers Squibb (Inst), Genentech/Roche (Inst), Iovance Biotherapeutics (Inst). SP: consultation/advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Foundation Medicine, Illumina, Janssen, Merck Sharp & Dohme, Merck Serono, Merrimack, Novartis, PharmaMar, Pfizer, Regeneron, Roche/Genentech, Sanofi, Seattle Genetics, Takeda, and Vaccibody; talk in a company's organized public event: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Illumina, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Sanofi, Takeda; research finding: Amgen (Inst), AstraZeneca (Inst), Biodesix (inst), Boehringer Ingelheim (inst), Bristol Myers Squibb (Inst), Clovis (Inst), Illumina (Inst), Merck Sharp & Dohme (Inst), Merck Serono (Inst), Novartis (Inst), Pfizer (Inst), and Roche/Genentech (Inst). LH: consulting or advisory role: AbbVie, AstraZeneca, Bristol Myers Squibb, EMB Serono, Genentech/Roche, Incyte, Merck, Xcovery; research funding: Boehringer Ingelheim, Bristol Myers Squibb, Xcovery. CA-V: consulting or advisory role: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Takeda; travel, accommodations, expenses: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Takeda. NPA: Consulting or advisory role: Merck Sharp & Dohme, Pfizer, Roche; travel, accommodations, expenses: Eli Lilly, Pfizer, Roche. OJ-V: honoraria: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Genentech/Roche, Merck Sharp & Dohme; consulting or advisory role: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Genentech/Roche, Merck Sharp & Dohme, Pfizer, Takeda; travel, accommodations, expenses: Merck Sharp & Dohme, Roche. MS: speaker's bureau: Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital. JW: honoraria: AbbVie, Amgen, AstraZeneca, Blueprint, Bristol Myers Squibb, Boehringer Ingelheim, Chugai, Eli Lilly, Ignyta, Janssen, Loxo, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda; research funding: Bristol Myers Squibb, Johnson and Johnson, Novartis, Pfizer. SA: consulting or advisory role: Achilles Therapeutics, Amgen, AstraZeneca, Bristol Myers Squibb, Cellular Biomedicine Group, Celsius, GlaxoSmithKline, Memgen, Merck, RAPT Therapeutics, Samyang Biopharm, Venn Therapeutics; travel, accommodations, expenses: Achilles Therapeutics, Amgen, Bristol Myers Squibb, Celsius, GlaxoSmithKline, Merck, RAPT Therapeutics. KN: honoraria: Astellas Pharma, AstraZeneca K.K., Bristol Myers Squibb, Carenet Health, Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., Hisamitsu Pharmaceutical Co., Inc., KYORIN Pharmaceutical Co., Ltd., Medical Review Co., Ltd., MEDICUS SHUPPAN Publishers Co., Ltd., Merck Sharp & Dohme K.K., Nanzando Co., Ltd., Nichi-Iko Pharmaceutical Co., Ltd., Nikkei Business Publications, Inc., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., ONO Pharmaceutical Co., Ltd., Pfizer Japan Inc., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd, Thermo Fisher Scientific K.K., YODOSHA Co., Ltd., Yomiuri Telecasting Corporation; consulting or advisory role: Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd; research funding: AbbVie, Astellas Pharma, AstraZeneca K.K., Bayer Yakuhin, Ltd., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., CMIC Shift Zero K.K., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., EPS Corporation, IQVIA., ICON Japan K.K., Kissei Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Merck Serono Co., Ltd., Merck Sharp & Dohme K.K., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., ONO Pharmaceutical Co., Ltd., Parexel International Corp., Pfizer Japan Inc., Quintiles Inc., SymBio Pharmaceuticals Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd. JF: former employee of Bristol Myers Squibb. CB employment: Bristol Myers Squibb. DP employment: Bristol Myers Squibb. PD employment: Bristol Myers Squibb, former employee of Johnson and Johnson. HC employment: Bristol Myers Squibb. MR: consulting or advisory role: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda; speaker's bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda; research funding: Boehringer Ingelheim, Bristol Myers Squibb; travel, accommodations, expenses: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda. All other authors have declared no conflicts of interest. Data sharing Bristol Myers Squibb policy on data sharing may be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html.

Auteurs

D R Spigel (DR)

Oncology Department, Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, USA. Electronic address: David.spigel@sarahcannon.com.

D Vicente (D)

Department of Medical Oncology, Hosp Univ Virgen Macarena, Seville, Spain.

T E Ciuleanu (TE)

Medical Oncology, Prof. Dr. Ion Chiricuta Institute of Oncology and UMF Iuliu Hatieganu, Cluj-Napoca, Romania.

S Gettinger (S)

Medical Oncology, Yale Cancer Center, New Haven, USA.

S Peters (S)

Oncology Department, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

L Horn (L)

Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, USA.

C Audigier-Valette (C)

Pulmonology Department, Hôpital Sainte Musse, Toulon, France.

N Pardo Aranda (N)

Thoracic Unit, Medical Oncology Department, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Barcelona.

O Juan-Vidal (O)

Department of Medical Oncology, Hospital Universitario La Fe, Valencia, Spain.

Y Cheng (Y)

Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, Jilin, China.

H Zhang (H)

Department of Oncology, Tangdu Hospital, Xi'an, Shaanxi, China.

M Shi (M)

Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.

A Luft (A)

Department of Thoracic Surgery, Leningrad Regional Clinical Hospital, St. Petersburg, Russian Federation.

J Wolf (J)

Clinic I for Internal Medicine, Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany.

S Antonia (S)

Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, USA.

K Nakagawa (K)

Department of Medical Oncology, Kindai University Hospital, Osaka, Japan.

J Fairchild (J)

Clinical Development, Bristol Myers Squibb, Princeton, USA.

C Baudelet (C)

Global Drug Development, Biometrics & Data Sciences, Bristol Myers Squibb, Princeton, USA.

D Pandya (D)

Translational Pathology, Bristol Myers Squibb, Princeton, USA.

P Doshi (P)

Translational Medicine, Bristol Myers Squibb, Princeton, USA.

H Chang (H)

Translational Bioinformatics, Bristol Myers Squibb, Princeton, USA.

M Reck (M)

Thoracic Oncology, LungenClinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany.

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Classifications MeSH

questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Association de médicaments › Protocoles de polychimiothérapie antinéoplasique › Second-line nivolumab in relapsed small-cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Second-line nivolumab in relapsed small-cell...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Second-line nivolumab in relapsed small-cell...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Récidive tumorale locale › Second-line nivolumab in relapsed small-cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Nivolumab › Second-line nivolumab in relapsed small-cell...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Survie sans progression › Second-line nivolumab in relapsed small-cell...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Tumeurs des bronches › Carcinome bronchogénique › Carcinome pulmonaire à petites cellules › Second-line nivolumab in relapsed small-cell...