Circulating Tumor DNA as a Prognostic Determinant in Small Cell Lung Cancer Patients Receiving Atezolizumab
- Creators
- Herbreteau, Guillaume
- Langlais, Alexandra
- Greillier, Laurent
- Audigier-Valette, Clarisse
- Uwer, Lionel
- Hureaux, José
- Moro-Sibilot, Denis
- Guisier, Florian
- Carmier, Delphine
- Madelaine, Jeannick
- Otto, Josiane
- Souquet, Pierre-Jean
- Gounant, Valérie
- Merle, Patrick
- Molinier, Olivier
- Renault, Aldo
- Rabeau, Audrey
- Morin, Franck
- Denis, Marc
- Pujol, Jean-Louis
- Others:
- Centre hospitalier universitaire de Nantes (CHU Nantes)
- Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT) ; Intergroupe Francophone de Cancérologie thoracique
- Assistance Publique - Hôpitaux de Marseille (APHM)
- Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse
- Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL) ; UNICANCER
- Centre Hospitalier Universitaire d'Angers (CHU Angers) ; PRES Université Nantes Angers Le Mans (UNAM)
- CHU Grenoble
- Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen] ; Hôpital Charles Nicolle [Rouen]-CHU Rouen ; Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN) ; Normandie Université (NU)
- Hôpital Bretonneau ; Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
- Service de pneumologie [CHU Caen] ; Université de Caen Normandie (UNICAEN) ; Normandie Université (NU)-Normandie Université (NU)-CHU Caen ; Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)
- Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL) ; UNICANCER-Université Côte d'Azur (UCA)
- Service de pneumologie [Centre Hospitalier Lyon Sud - HCL] ; Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS) ; Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)
- Service d'oncologie thoracique et essais précoces [CHU Bichat] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- CHU Clermont-Ferrand
- Centre Hospitalier Le Mans (CH Le Mans)
- Centre hospitalier de Pau
- Service de pneumologie [Toulouse] ; CHU Toulouse [Toulouse]
- Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
- Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM) ; CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Description
Background: The IFCT-1603 trial evaluated atezolizumab in small cell lung cancer (SCLC). The purpose of the present study was to determine whether circulating tumor DNA (ctDNA), prospectively collected at treatment initiation, was associated with the prognosis of SCLC, and whether it identified patients who benefited from atezolizumab.Methods: 68 patients were included in this study: 46 patients were treated with atezolizumab and 22 with conventional chemotherapy. Circulating DNA was extracted from plasma and NGS (Next Generation Sequencing) looked for mutations in the TP53, RB1, NOTCH1, NOTCH2, and NOTCH3 genes. ctDNA was detectable when at least one somatic mutation was identified, and its relative abundance was quantified by the variant allele fraction (VAF) of the most represented mutation.Results: We found that 49/68 patients (70.6%) had detectable baseline ctDNA. The most frequently identified mutations were TP53 (32/49; 65.3%) and RB1 (25/49; 51.0%). Patients with detectable ctDNA had a significantly lower disease control rate at week 6 compared with patients with no detectable ctDNA, regardless of the nature of the treatment. Detection of ctDNA was associated with a poor OS prognosis. The detection of ctDNA at a relative abundance greater than the median value was significantly associated with poor overall survival (OS) and progression free survival (PFS). Interestingly, the benefit in overall survival (OS) associated with low ctDNA was more pronounced in patients treated with atezolizumab than in patients receiving chemotherapy. Among patients whose relative ctDNA abundance was below the median, those treated with atezolizumab tended to have higher OS than those in the chemotherapy arm.Conclusion: ctDNA is strongly associated with the prognosis of SCLC patients treated with second-line immunotherapy. Its analysis seems justified for future SCLC clinical trials.
Abstract
International audience
Additional details
- URL
- https://hal.umontpellier.fr/hal-03222725
- URN
- urn:oai:HAL:hal-03222725v1
- Origin repository
- UNICA