Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial

Large genomic programs have contributed to improving drug development in cancer. To assess the potential benefit of using larger gene panels to guide molecular-based treatments, we conducted a multicenter randomized trial in patients with advanced and/or metastatic solid cancer. Molecular alterations were determined using either a panel of 324 cancer-related genes (Foundation OneCDX (F1CDX)) or a limited panel of 87 single-nucleotide/indel genes and genome-wide copy number variations (CTL) and reviewed by a molecular tumor board to identify molecular-based recommended therapies (MBRTs). Using paired data from both panels for each patient, the primary endpoint was the proportion of patients with an MBRT identified. Main secondary endpoints included the number of patients with at least one actionable alteration leading to MBRT identification, the number of patients with and without MBRTs initiated, progression-free survival, best overall response, duration of response and safety. Among the 741 patients screened, 45.7% had quality-checked tumor samples. MBRTs were identified with F1CDX in 175 (51.6%) patients and with CTL in 125 (36.9%) patients, translating to a significant increase of 14.8 percentage points (P < 0.001) with the more comprehensive gene panel versus the more limited panel, meeting the primary endpoint. However, no differences in clinical outcomes were observed in these patients with advanced and/or metastatic cancer in need of treatment beyond standard genomic alterations. These findings illustrate the potential for larger gene panels to increase the number of molecularly matched therapies. Larger studies are needed to assess the clinical benefit of expanded MBRTs. ClinicalTrials.gov registration: NCT03163732 .

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Publication Details

Journal
Nature Medicine
Published
2025-04-07
DOI
https://doi.org/10.1038/s41591-025-03613-x
Citations
9
Primary Topic
Cancer Genomics and Diagnostics
Type
article
Field-Weighted Citation Impact
8.43

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article

Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial

Carlos Gomez‐Roca, Sandrine Boyault, David Pérol, Olivier Trédan et al.
9 citations
Nature Medicine
Cancer Genomics and Diagnostics
8.43
article

Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial

Carlos Gomez‐Roca, Sandrine Boyault, David Pérol, Olivier Trédan, Philippe A. Cassier, Marie-Eve Garcia, Diane Pannier, Diégo Tosi, Alain Viari, Jean‐Yves Blay, Armelle Dufresne, Sylvie Chabaud, Nicolas Penel, Marie Viala, Antoîne Italiano, Delphine Larrieu‐Ciron, Valéry Attignon, Isabelle Laure Ray-Coquard, Damien Pouessel, Mehdi Brahmi, Isabelle Treilleux, Michel Fabbro, Jean-Pierre Delord
article en
9 citations

Abstract

Large genomic programs have contributed to improving drug development in cancer. To assess the potential benefit of using larger gene panels to guide molecular-based treatments, we conducted a multicenter randomized trial in patients with advanced and/or metastatic solid cancer. Molecular alterations were determined using either a panel of 324 cancer-related genes (Foundation OneCDX (F1CDX)) or a limited panel of 87 single-nucleotide/indel genes and genome-wide copy number variations (CTL) and reviewed by a molecular tumor board to identify molecular-based recommended therapies (MBRTs). Using paired data from both panels for each patient, the primary endpoint was the proportion of patients with an MBRT identified. Main secondary endpoints included the number of patients with at least one actionable alteration leading to MBRT identification, the number of patients with and without MBRTs initiated, progression-free survival, best overall response, duration of response and safety. Among the 741 patients screened, 45.7% had quality-checked tumor samples. MBRTs were identified with F1CDX in 175 (51.6%) patients and with CTL in 125 (36.9%) patients, translating to a significant increase of 14.8 percentage points (P < 0.001) with the more comprehensive gene panel versus the more limited panel, meeting the primary endpoint. However, no differences in clinical outcomes were observed in these patients with advanced and/or metastatic cancer in need of treatment beyond standard genomic alterations. These findings illustrate the potential for larger gene panels to increase the number of molecularly matched therapies. Larger studies are needed to assess the clinical benefit of expanded MBRTs. ClinicalTrials.gov registration: NCT03163732 .

Nature MedicineVol. 31(5)
Université Claude Bernard Lyon 1 (FR), Institut national de recherche en sciences et technologies du numérique (FR), Assistance Publique Hôpitaux de Marseille (FR), Centre Léon Bérard (FR), Centre de Recherche en Cancérologie de Lyon (FR), Institut Claudius Regaud (FR), Centre Oscar Lambret (FR), Institut Bergonié (FR), Institut de Recherche en Cancérologie de Montpellier (FR)
Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation ARC pour la Recherche sur le Cancer, Ligue Contre le Cancer, Institut National Du Cancer, Direction Générale de l’offre de Soins, Centre Léon Bérard, LabEx DEvweCAN, Foundation Medicine, European Network for Rare Adult Solid Cancers
Good health and well-being
Openalex Percentile: Top 2%
Cancer Genomics and Diagnostics
8.43
DOIOpen Access PDFOpenAlex
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