ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
05 2022
Historique:
received: 31 01 2022
accepted: 02 02 2022
pubmed: 15 3 2022
medline: 27 4 2022
entrez: 14 3 2022
Statut: ppublish

Résumé

Now that immunotherapy plus chemotherapy (CT) is one standard option in first-line treatment of advanced non-small cell lung cancer (NSCLC), there exists a medical need to assess the efficacy of second-line treatments (2LT) with antiangiogenics (AA). We performed an individual patient data meta-analysis to validate the efficacy of these combinations as 2LT. Randomised trials of AA plus standard 2LT compared to 2LT alone that ended accrual before 2015 were eligible. Fixed-effect models were used to compute pooled hazard ratios (HRs) for overall survival (OS, main end-point), progression-free survival (PFS) and subgroup analyses. Sixteen trials were available (8,629 patients, 64% adenocarcinoma). AA significantly prolonged OS (HR = 0.93 [95% confidence interval {CI}: 0.89; 0.98], p = 0.005) and PFS (0.80 [0.77; 0.84], p < 0.0001) compared with 2LT alone. Absolute 1-year OS and PFS benefit for AA were +1.8% [-0.4; +4.0] and +3.5% [+1.9; +5.1], respectively. The OS benefit of AA was higher in younger patients (HR = 0.87 [95% CI: 0.76; 1.00], 0.89 [0.81; 0.97], 0.94 [0.87; 1.02] and 1,04 [0.93; 1.17] for patients <50, 50-59, 60-69 and ≥ 70 years old, respectively; trend test: p = 0.02) and in patients who started AA within 9 months after starting the first-line therapy (0.88 [0.82; 0.99]) than in patients who started AA later (0.99 [0.91; 1.08]) (interaction: p = 0.03). Results were similar for PFS. AA increased the risk of hypertension (p < 0.0001), but not the risk of pulmonary thromboembolic events (p = 0.21). In the 2LT of advanced NSCLC, adding AA significantly prolongs OS and PFS, but the benefit is clinically limited, mainly observed in younger patients and after shorter time since the start of first-line therapy.

Sections du résumé

BACKGROUND
Now that immunotherapy plus chemotherapy (CT) is one standard option in first-line treatment of advanced non-small cell lung cancer (NSCLC), there exists a medical need to assess the efficacy of second-line treatments (2LT) with antiangiogenics (AA). We performed an individual patient data meta-analysis to validate the efficacy of these combinations as 2LT.
METHODS
Randomised trials of AA plus standard 2LT compared to 2LT alone that ended accrual before 2015 were eligible. Fixed-effect models were used to compute pooled hazard ratios (HRs) for overall survival (OS, main end-point), progression-free survival (PFS) and subgroup analyses.
RESULTS
Sixteen trials were available (8,629 patients, 64% adenocarcinoma). AA significantly prolonged OS (HR = 0.93 [95% confidence interval {CI}: 0.89; 0.98], p = 0.005) and PFS (0.80 [0.77; 0.84], p < 0.0001) compared with 2LT alone. Absolute 1-year OS and PFS benefit for AA were +1.8% [-0.4; +4.0] and +3.5% [+1.9; +5.1], respectively. The OS benefit of AA was higher in younger patients (HR = 0.87 [95% CI: 0.76; 1.00], 0.89 [0.81; 0.97], 0.94 [0.87; 1.02] and 1,04 [0.93; 1.17] for patients <50, 50-59, 60-69 and ≥ 70 years old, respectively; trend test: p = 0.02) and in patients who started AA within 9 months after starting the first-line therapy (0.88 [0.82; 0.99]) than in patients who started AA later (0.99 [0.91; 1.08]) (interaction: p = 0.03). Results were similar for PFS. AA increased the risk of hypertension (p < 0.0001), but not the risk of pulmonary thromboembolic events (p = 0.21).
CONCLUSIONS
In the 2LT of advanced NSCLC, adding AA significantly prolongs OS and PFS, but the benefit is clinically limited, mainly observed in younger patients and after shorter time since the start of first-line therapy.

Identifiants

pubmed: 35286903
pii: S0959-8049(22)00075-2
doi: 10.1016/j.ejca.2022.02.002
pii:
doi:

Substances chimiques

Angiogenesis Inhibitors 0

Types de publication

Journal Article Meta-Analysis Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

112-125

Investigateurs

B Besse (B)
B Lacas (B)
J P Pignon (JP)
J Remon (J)
T Berghmans (T)
S Dahlberg (S)
E Felip (E)
Thierry Berghmans (T)
Benjamin Besse (B)
Suzanne Dahlberg (S)
Enriqueta Felip (E)
Edward Garon (E)
Harry J M Groen (HJM)
Nasser Hanna (N)
Rebecca S Heist (RS)
Roy Herbst (R)
John V Heymach (JV)
Benjamin Lacas (B)
Alex A Adjei (AA)
Rebecca Heist (R)
Sumithra J Mandrekar (SJ)
Joel W Neal (JW)
Isamu Okamoto (I)
Jean-Pierre Pignon (JP)
Rodryg Ramlau (R)
Jordi Remon (J)
Martin Reck (M)
Giorgio V Scagliotti (GV)
Johan Vansteenkiste (J)
Kiyotaka Yoh (K)

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement RH, MR, EBG, GVS, RR, NH, JV, KY, HG, JH and RH are authors for some of the trials included in this meta-analysis. Other authors have not reported any conflict of interest related to this study.

Auteurs

Jordi Remon (J)

Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France.

Benjamin Lacas (B)

Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, Oncostat U1018 INSERM, Labeled Ligue Contre le Cancer, Université Paris-Saclay, Villejuif, France.

Roy Herbst (R)

Yale School of Medicine, New Haven, CT, USA.

Martin Reck (M)

Lung Clinic, Airway Research Center North (ARCN), German Center for Lung Research, Germany.

Edward B Garon (EB)

David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Giorgio V Scagliotti (GV)

Department of Oncology, University of Turin, Italy.

Rodryg Ramlau (R)

Poznan University of Medical Sciences, Poznan, Poland.

Nasser Hanna (N)

Indiana University, Indianapolis, IN, USA.

Johan Vansteenkiste (J)

University Hospital KU Leuven, Leuven, Belgium.

Kiyotaka Yoh (K)

National Cancer Center Hospital East, Kashiwa, Japan.

Harry J M Groen (HJM)

University of Groningen and University Medical Center Groningen, the Netherlands.

John V Heymach (JV)

The University of Texas MD Anderson Cancer Center, USA.

Sumithra J Mandrekar (SJ)

Department of Quantitative Health Sciences, Mayo Clinic, Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, USA.

Isamu Okamoto (I)

Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Joel W Neal (JW)

Stanford Cancer Institute/Stanford University, Stanford, CA, USA.

Rebecca S Heist (RS)

Massachusetts General Hospital Cancer Center, Boston, MA, USA.

David Planchard (D)

Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France.

Jean-Pierre Pignon (JP)

Service de Biostatistique et d'Epidémiologie, Gustave Roussy Cancer Campus, Oncostat U1018 INSERM, Labeled Ligue Contre le Cancer, Université Paris-Saclay, Villejuif, France.

Benjamin Besse (B)

Département d'Oncologie Médicale, Gustave Roussy, Villejuif, France; Paris-Sud University, France. Electronic address: Benjamin.BESSE@gustaveroussy.fr.

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