Mariona Riudavets1, Edouard Auclin2, Miguel Mosteiro3, Naomi Dempsey4, Margarita Majem5, Riccardo Lobefaro6, Rafael López-Castro7, Joaquim Bosch-Barrera8, Sara Pilotto9, Elena Escalera10, Marco Tagliamento11, Joaquin Mosquera12, Gerard Zalcman13, Frank Aboubakar-Nana14, Santiago Ponce15, Alessandro Dal Maso16, Martina Spotti17, Xabier Mielgo-Rubio18, Elodie Mussat2, Roxana Reyes19, José-Carlos Benítez20, Lorena Lupinacci21, Boris Duchemann22, Andrea De Giglio23, Juan Blaquier24, Clarisse Audigier-Valette25, Matthias Scheffler26, Ernest Nadal3, Gilberto Lopes4, Diego Signorelli6, Rosario Garcia-Campelo12, Jessica Menis27, Virginia Bluthgen17, Marc Campayo28, Gonzalo Recondo24, Benjamin Besse1, David Planchard29, Laura Mezquita30. 1. Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France. 2. Medical Oncology Department, Hôpital Européen Georges Pompidou, AP-HP Centre, Université de Paris, Paris, France. 3. Medical Oncology Department, Institut Català d'Oncologia - ICO Hospitalet, Barcelona, Spain. 4. Medical Oncology Department, Jackson Memorial Hospital, Miami, FL, USA. 5. Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 6. Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milan, Milano, Italy. 7. Medical Oncology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain. 8. Medical Oncology Department, Catalan Institute of Oncology, Hospital Universitari Josep Trueta, Girona, Spain. 9. Medical Oncology Department, University and Hospital Trust of Verona, Verona, Italy. 10. Medical Oncology Department, Hospital Clínico de Salamanca, Salamanca, Spain. 11. Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France; Internal Medicine and Medical Specialties Departement, University of Genova, Genova, Italy. 12. Medical Oncology Department, Hospital Universitario A Coruña, A Coruña, Spain. 13. Medical Oncology Department, Hôpital Bichat-Claude Bernard, Paris, France. 14. Division of Pneumology, Cliniques universitaires Saint-Luc, Bruxelles, Belgium. 15. Medical Oncology Department, Hospital 12 de Octubre, Madrid, Spain. 16. Medical Oncology Department, Istituto Oncologico Veneto IRCCS, Padova, Italy. 17. Medical Oncology Department, Hospital Aleman, Buenos Aires, Argentina. 18. Medical Oncology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain. 19. Medical Oncology Department, Hospital Clínic i Provincial de Barcelona, IDIBAPS, Barcelona, Spain. 20. Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France; Medical Oncology Department, Hospital Universitari Mutua Terrassa, Terrassa, Barcelona, Spain. 21. Medical Oncology Department, Hospital Italiano, Buenos Aires, Argentina. 22. Medical Oncology Department, Hôpital Avicenne, Bobigny, France. 23. Medical Oncology Department, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 24. Medical Oncology Department, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina. 25. Medical Oncology Department, Centre Hospitalier Toulon Sainte-Mousse, Toulon, France. 26. Internal Medicine I Department, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. 27. Medical Oncology Department, University and Hospital Trust of Verona, Verona, Italy; Medical Oncology Department, Istituto Oncologico Veneto IRCCS, Padova, Italy. 28. Medical Oncology Department, Hospital Universitari Mutua Terrassa, Terrassa, Barcelona, Spain. 29. Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: David.PLANCHARD@gustaveroussy.fr. 30. Medical Oncology Department, Hospital Clínic i Provincial de Barcelona, IDIBAPS, Barcelona, Spain; Medical Oncology Department, Laboratory of Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain.
Abstract
INTRODUCTION: Durvalumab is the standard-of-care as consolidation therapy after chemo-radiotherapy in stage III unresectable non-small cell lung cancer (NSCLC); however, its activity across patients with NSCLC harbouring driver genomic alterations (dGA) is poorly characterised. MATERIAL AND METHODS: Multicentre retrospective study including patients with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and October 2020 at 26 centres in Europe and America. Clinical and biological data were collected; dGA included: EGFR/BRAF/KRAS mutations (m) and ALK/ROS1 rearrangements (r). We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA. RESULTS: Out of 323 patients included, 43 patients had one dGA: KRASm (n = 26; 8 G12C), EGFRm (n = 8; 6 del19/ex21), BRAFm (n = 5; 4 V600E) and ALKr (n = 4). The median age was 66 years [39-84], gender ratio 1:1, with 98% performance status (PS) 0-1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n = 4 missing). In the whole cohort, the median PFS was 17.5 months (mo.) (95% CI, 13.2-24.9) and median OS 47 mo (95%CI, 47-not reached [NR]). No statistically significant differences in terms of the median PFS were observed between patients with dGA vs. non-dGA: 14.9 mo (95% CI, 8.1-NR) vs. 18 mo. (95% CI, 13.4-28.3) (P = 1.0); however, when analysed separately: the median PFS was NR (11.3-NR) in the KRASm G12C vs. 8.1 mo (5.8-NR) in the EGFRm del19/ex21 vs. 7.8 mo (7.7-NR) in the BRAFm V600E/ALKr (P = 0.02). CONCLUSIONS: We observed limited activity of durvalumab consolidation in patients with stage III unresectable NSCLC with EGFR/BRAFm and ALKr but not for those harbouring KRASm. Larger prospective studies are needed to confirm these findings.
INTRODUCTION: Durvalumab is the standard-of-care as consolidation therapy after chemo-radiotherapy in stage III unresectable non-small cell lung cancer (NSCLC); however, its activity across patients with NSCLC harbouring driver genomic alterations (dGA) is poorly characterised. MATERIAL AND METHODS: Multicentre retrospective study including patients with stage III unresectable NSCLC treated with durvalumab after chemo-radiotherapy between April 2015 and October 2020 at 26 centres in Europe and America. Clinical and biological data were collected; dGA included: EGFR/BRAF/KRAS mutations (m) and ALK/ROS1 rearrangements (r). We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA. RESULTS: Out of 323 patients included, 43 patients had one dGA: KRASm (n = 26; 8 G12C), EGFRm (n = 8; 6 del19/ex21), BRAFm (n = 5; 4 V600E) and ALKr (n = 4). The median age was 66 years [39-84], gender ratio 1:1, with 98% performance status (PS) 0-1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n = 4 missing). In the whole cohort, the median PFS was 17.5 months (mo.) (95% CI, 13.2-24.9) and median OS 47 mo (95%CI, 47-not reached [NR]). No statistically significant differences in terms of the median PFS were observed between patients with dGA vs. non-dGA: 14.9 mo (95% CI, 8.1-NR) vs. 18 mo. (95% CI, 13.4-28.3) (P = 1.0); however, when analysed separately: the median PFS was NR (11.3-NR) in the KRASm G12C vs. 8.1 mo (5.8-NR) in the EGFRm del19/ex21 vs. 7.8 mo (7.7-NR) in the BRAFm V600E/ALKr (P = 0.02). CONCLUSIONS: We observed limited activity of durvalumab consolidation in patients with stage III unresectable NSCLC with EGFR/BRAFm and ALKr but not for those harbouring KRASm. Larger prospective studies are needed to confirm these findings.