Comprehensive Genome Profiling in Patients With Metastatic Non-Small Cell Lung Cancer: The Precision Medicine Phase II Randomized SAFIR02-Lung Trial - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue CLINICAL CANCER RESEARCH Année : 2022

Comprehensive Genome Profiling in Patients With Metastatic Non-Small Cell Lung Cancer: The Precision Medicine Phase II Randomized SAFIR02-Lung Trial

1 Fondation Synergie Lyon Cancer [Lyon]
2 Centre Léon Bérard [Lyon]
3 Institut Bergonié [Bordeaux]
4 CHU Angers - Centre Hospitalier Universitaire d'Angers
5 CRCI2NA - Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers
6 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
7 PMNCO - Prédicteurs moléculaires et nouvelles cibles en oncologie
8 CIC 1428 , CBT 507 - Centre d'Investigation Clinique en Biotherapie des cancers
9 UNICANCER
10 Département de médecine oncologique [Gustave Roussy]
11 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
12 IGR - Institut Gustave Roussy
13 CRCM - Centre de Recherche en Cancérologie de Marseille
14 OMIT - Multidisciplinary Oncology and Therapeutic Innovations Unit / Service d’Oncologie Multidisciplinaire et d’Innovations Thérapeutiques
15 Tarbiat Modares University [Tehran]
16 SBE - Service de biostatistique et d'épidémiologie
17 U1018 (Équipe 2) - Oncostat
18 Institut Curie [Paris]
19 Service de Pneumologie [CHU Clermont-Ferrand]
20 IPC - Institut Paoli-Calmettes
21 Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse
22 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
23 Service de pneumologie [Toulouse]
24 CHU de Grenoble-Alpes
25 UNICANCER/Lille - Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille]
26 Centre Hospitalier Le Mans (CH Le Mans)
27 IFCT - Intergroupe Francophone de Cancérologie Thoracique [Paris]
28 CHRO - Centre Hospitalier Régional d'Orléans
29 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
30 SIRIC-ONCOLille - Site de Recherche Intégrée en Cancérologie
31 UniCA - Université Côte d'Azur
32 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
33 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
34 Centre Hospitalier Henri Duffaut (Avignon)
35 BECCOH - Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie
36 Département de biologie et pathologie médicales [Gustave Roussy]
Filippo Gustavo Dall'Olio
  • Fonction : Auteur
Marta Jimenez
  • Fonction : Auteur
Maryam Karimi
Ivan Bieche

Résumé

Purpose: Targeted therapies (TT) and immune checkpoint blockers (ICB) have revolutionized the approach to non-small cell lung cancer (NSCLC) treatment in the era of precision medicine. Their impact as switch maintenance therapy based on molecular characterization is unknown.Patients and Methods: SAFIR02-Lung was an open-label, randomized, phase II trial, involving 33 centers in France. We investigated eight TT (substudy-1) and one ICB (substudy-2), compared with standard-of-care as a maintenance strategy in patients with advanced EGFR, ALK wild-type (wt) NSCLC without progression after first-line chemotherapy, based on high-throughput genome analysis. The primary outcome was progression-free survival (PFS).Results: Among the 175 patients randomized in substudy-1, 116 received TT (selumetinib, vistusertib, capivasertib, AZD4547, AZD8931, vandetanib, olaparib, savolitinib) and 59 standard-of-care. Median PFS was 2.7 months [95% confidence interval (CI), 1.6-2.9] with TT versus 2.7 months (1.6-4.1) with standard-of-care (HR, 0.97; 95% CI, 0.7-1.36; P = 0.87). There were no significant differences in PFS within any molecular subgroup. In substudy-2, 183 patients were randomized, 121 received durvalumab and 62 standard-of-care. Median PFS was 3.0 months (2.3-4.4) with durvalumab versus 3.0 months (2.0-5.1) with standard-of-care (HR, 0.86; 95% CI, 0.62-1.20; P = 0.38). Preplanned subgroup analysis showed an enhanced benefit with durvalumab in patients with PD-L1 tumor proportion score (TPS) >= 1%, (n = 29; HR, 0.29; 95% CI, 0.11-0.75) as compared with PD-L1 < 1% (n = 31; HR, 0.71; 95% CI, 0.31-1.60; P-interaction = 0.036). Conclusions: Molecular profiling can feasibly be implemented to guide treatment choice for the maintenance strategy in EGFR/ALK wt NSCLC; in this study it did not lead to substantial treatment benefits beyond durvalumab for PD-L1 >= 1 patients.

Dates et versions

hal-04084975 , version 1 (28-04-2023)

Identifiants

Citer

Sandrine Boyault, Valery Attignon, Isabelle Soubeyran, Alain Morel, Alicia Tran-Dien, et al.. Comprehensive Genome Profiling in Patients With Metastatic Non-Small Cell Lung Cancer: The Precision Medicine Phase II Randomized SAFIR02-Lung Trial. CLINICAL CANCER RESEARCH, 2022, 28 (18), pp.4018-4026. ⟨10.1158/1078-0432.CCR-22-0371⟩. ⟨hal-04084975⟩
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