Molecular Profiles of Advanced Urological Cancers in the PERMED-01 Precision Medicine Clinical Trial

Autor: Emilien Billon, Gwenaelle Gravis, Arnaud Guille, Nadine Carbuccia, Jose Adelaide, Séverine Garnier, Pascal Finetti, Emilie Denicolaï, Patrick Sfumato, Serge Brunelle, Jeanne Thomassin-Piana, Géraldine Pignot, Jochen Walz, Christian Chabannon, Jihane Pakradouni, Renaud Sabatier, Cécile Vicier, Cornel Popovici, Emilie Mamessier, Anthony Gonçalves, Daniel Birnbaum, Max Chaffanet, François Bertucci
Přispěvatelé: Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre d'Investigations Cliniques en Biothérapies [Marseille], Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)
Rok vydání: 2022
Předmět:
Zdroj: Cancers; Volume 14; Issue 9; Pages: 2275
Cancers
Cancers, 2022, 14 (9), ⟨10.3390/cancers14092275⟩
ISSN: 2072-6694
DOI: 10.3390/cancers14092275⟩
Popis: Simple Summary The goal of precision medicine is to deliver therapy matched to a relevant actionable genetic alteration (AGA) identified in the tumor. Few data are available regarding precision medicine in advanced urological cancers (AUC), the prognosis of which remains unfavorable. Sixty-four patients with refractory AUC were enrolled in the PERMED-01 clinical trial and underwent a tumor biopsy that was then profiled using sophisticated molecular analyses. The results were discussed in real-time during a weekly molecular tumor board meeting, and patients with a relevant AGA became candidates for an eventual matched therapy. A complete molecular profile was obtained in 77% of cases and an AGA was identified in 59%. Nineteen percent of patients received a matched therapy on progression, of which 42% showed a clinical benefit. The objective response, disease control rates, and the 6-year overall survival were higher in the ``matched therapy group'' than in the ``non-matched therapy group''. Introduction. The prognosis of advanced urological cancers (AUC) remains unfavorable, and few data are available regarding precision medicine. Methods: the PERMED-01 prospective clinical trial assessed the impact of molecular profiling in adults with refractory advanced solid cancer, in terms of number of patients with tumor actionable genetic alterations (AGA), feasibility, description of molecular alterations, treatment, and clinical outcome. We present here those results in the 64 patients enrolled with AUC. DNA extracted from a new tumor biopsy was profiled in real-time (targeted NGS, whole-genome array-comparative genomic hybridization), and the results were discussed during a weekly molecular tumor board meeting. Results: a complete molecular profile was obtained in 49 patients (77%). Thirty-eight (59%) had at least one AGA. Twelve (19%) received a matched therapy on progression, of which 42% had a PFS2/PFS1 ratio >= 1.3 versus 5% in the ``non-matched therapy group'' (n = 25). The objective response and disease control rates were higher in the ``matched therapy group'' (33% and 58%, respectively) than in the ``non-matched therapy group'' (13% and 22%), as was the 6-month OS (75% vs. 42%). Conclusion: the profiling of a newly biopsied tumor sample identified AGA in 59% of patients with AUC, led to ``matched therapy'' in 19%, and provided clinical benefit in 8%.
Databáze: OpenAIRE
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