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Publications

Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't Ppublish 7 citations

PubMed: 35802649 DOI: 10.1158/1078-0432.CCR-22-0371

Comprehensive Genome Profiling in Patients With Metastatic Non-Small Cell Lung Cancer: The Precision Medicine Phase II Randomized SAFIR02-Lung/IFCT 1301 Trial.

Clin Cancer Res 28(18):4018-4026

Authors: Fabrice Barlesi, Pascale Tomasini, Maryam Karimi, Stefan Michiels, Judith Raimbourg, Catherine Daniel, Henri Janicot, Anne Madroszyk, Clarisse Audigier-Valette, Elisabeth Quoix, Julien Mazieres, Denis Moro-Sibilot, Eric Dansin, Olivier Molinier, Hugues Morel, Eric Pichon, Alexis Cortot, Josiane Otto, François Chomy, Pierre-Jean Souquet, Nicolas Cloarec, Etienne Giroux-Leprieur, Ivan Bieche, Ludovic Lacroix, Sandrine Boyault, Valery Attignon, Isabelle Soubeyran, Alain Morel, Alicia Tran-Dien, Alexandra Jacquet, Filippo Gustavo Dall'Olio, Marta Jimenez, Jean-Charles Soria, Benjamin Besse

Affiliations

  • Department of Medical Oncology, Gustave Roussy, Villejuif, France.
  • Aix Marseille University, CNRS, INSERM, CRCM, APHM, Multidisciplinary Oncology & Therapeutic Innovations Department, Marseille, France.
  • Office of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France.
  • Oncostat U1018, Inserm, University Paris-Saclay, labeled Ligue Contre le Cancer, Villejuif, France.
  • Department of Medical Oncology, ICO- Centre René Gauducheau, Nantes, France.
  • Department of Medical Oncology, Institut Curie, Paris, France.
  • Department of Medical Oncology, Centre Hospitalier Universitaire de Clermont-Ferrand - Hôpital Gabriel Montpied, Clermont-Ferrand, France.
  • Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.
  • Department of Medical Oncology, CHI de Toulon - Hôpital Sainte-Musse, Toulon, France.
  • Department of Pneumology, CHRU Strasbourg - Nouvel Hôpital Civil, Strasbourg, France.
  • Centre Hospitalier Universitaire de Toulouse - Hôpital Larrey, Toulouse, France.
  • Department of Physiology and Pneumology, CHU de Grenoble-Alpes, Grenoble, France.
  • Department of Medical Oncology, Centre Oscar Lambret, Lille, France.
  • Department of Pneumology, CH du Mans, Le Mans, France.
  • Department of Pneumology and Thoracic Oncology, CHR d'Orléans, Orléans, France.
  • Department of Pneumology, Hôpital Bretonneau, Tours, France.
  • Univ. Lille, CHU Lille, Lille, France.
  • Deparment of onco-pneumology, Centre Antoine Lacassagne Nice, France.
  • Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
  • Department of Pneumology, CH de Lyon Sud, Lyon, France.
  • Department of Onco-Hematology, Centre Hospitalier Henri Duffau, Avignon, France.
  • Deparment of Onco-Pneumology, Hôpital Ambroise Paré, Boulogne Billancourt, France.
  • Department of Genetics, Institut Curie and University of Paris, Paris, France.
  • Department of Medical Biology and Pathology, BMO unit, AMMICa UMS3655/US23, Gustave Roussy Cancer Campus, Villejuif, France.
  • Département de Recherche Translationnelle et d'Innovation, Centre Léon Bérard, Lyon, France.
  • Unité de Pathologie Molé30culaire - Département de Biopathologie, Institut Bergonié, Bordeaux, France.
  • Univ Angers, Université de Nantes, ICO Nantes Angers, Inserm, CRCINA, SFR ICAT, F-49000 Angers, France.
  • Inserm UMR981 and Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
  • Université Paris Saclay, Le Kremlin-Bicêtre, France.
  • Unicancer, Paris, France.

Abstract

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/IFCT 1301 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; Pinteraction = 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.

MeSH

Cells, Lung, Neoplasms, Carcinoma, Non-Small-Cell Lung, Genome, Maintenance, Lung Neoplasms, Small Cell Lung Carcinoma, Precision Medicine, Therapeutics

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