{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T05:18:23Z","timestamp":1787980703824,"version":"build-2784847793"},"reference-count":32,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ARISTOT"},{"name":"Association de l\u2019AIR"},{"name":"Roche"},{"DOI":"10.13039\/501100014546","name":"GFPC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014546","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Oncol.","Current Oncology"],"abstract":"<jats:p>Background: The sequential use of anti-programmed cell death (ligand)-1 [PD-(L)1] immune-checkpoint inhibitors (ICIs) followed by targeted tyrosine-kinase inhibitors (TKIs) for advanced non-small cell lung cancer (NSCLC) with oncogenic alterations raises questions about tolerance and efficacy. Recent study results suggested an increased risk of adverse events (AEs) with this sequence. Methods: Multicenter retrospective study on advanced NSCLC patients treated with ICIs followed by targeted therapies between 2015 and 2021. The primary endpoint was the rate of grade 3\u20135 adverse events (AEs). Main secondary endpoints were progression-free survival (PFS), time-to-treatment failure and overall survival (OS). Results: The analysis included 109 patients (most with EGFR, 30.3%; BRAF, 17.4%; MET exon-14, 17.4%; ALK, 10.1%; and RET, 6.4% gene alterations); 28\/109, which is 25.7% of the patients, experienced grade 3\/4 AEs and 4\/109 (3.7%) experienced grade 5 AEs, leading to the definitive cessation of targeted therapy treatment in 14\/32 (44%) of cases; higher grade 3\u20135 rates were observed with the dabrafenib\u2013trametinib combination (12\/16, 75%), capmatinib (4\/8, 50%) and crizotinib (8\/16, 50%). A last ICI-administration-to-targeted therapy-start interval of &lt;90 days appeared to be associated with grade \u2265 3 AEs (32\/82, 39% vs. 0\/27 p = 0.001). In these sequential strategies, effectiveness of targeted therapies, in this second-line or later setting, appears to be lower than that in the published historical data. Conclusion: According to this analysis, sequential ICI\u2013targeted therapy use for advanced NSCLC appeared to be associated with more grade 3\u20135 AEs.<\/jats:p>","DOI":"10.3390\/curroncol33090510","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:02:27Z","timestamp":1787817747000},"page":"510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tolerance and Efficacy of Targeted Therapies After Immunotherapy for Advanced Non-Small Cell Lung Cancers Harboring Oncogenic Alterations: The GFPC-TOXIMAD Study"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4297-7413","authenticated-orcid":false,"given":"Thomas","family":"Pierret","sequence":"first","affiliation":[{"name":"Departement of Pneumology, Louis Pradel Hospital, Hospices Civils de Lyon, 69500 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6400-7506","authenticated-orcid":false,"given":"Jean-Bernard","family":"Auliac","sequence":"additional","affiliation":[{"name":"Department of Pneumology, Centre Hospitalier Intercommunal de Cr\u00e9teil, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Ricordel","sequence":"additional","affiliation":[{"name":"Department of Pneumology, CHU Rennes, Univ Rennes 1, INSERM, OSS (Oncogenesis Stress Signaling), UMRS 1242, CLCC Eugene-Marquis, 35200 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Daniel","sequence":"additional","affiliation":[{"name":"Thoracic Oncology Service, Thorax Institute Curie Montsouris, Institut Curie, 75005 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Departement of Pneumology, CHU BREST, 29200 Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8166-7303","authenticated-orcid":false,"given":"Florian","family":"Guisier","sequence":"additional","affiliation":[{"name":"EA4108 LITIS Lab, QuantIF Team and Inserm CIC-CRB 1404, Service de Pneumologie, Oncologie Thoracique et Soins Intensifs Respiratoires, CHU Rouen, Normandie Universit\u00e9, UNIROUEN, 76031 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Swalduz","sequence":"additional","affiliation":[{"name":"Department of Pneumology, Comprehensive Cancer Centre L\u00e9on-B\u00e9rard, 28, Rue Laennec, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Curcio","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Comprehensive Cancer Center Fran\u00e7ois-Baclesse, 3, Avenue du G\u00e9n\u00e9ral Harris, 14076 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Laure","family":"Desage","sequence":"additional","affiliation":[{"name":"Department of Pneumology, CHU Saint-Etienne, 42100 Saint-Etienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Bigay-Game","sequence":"additional","affiliation":[{"name":"Department of Pneumology & Thoracic Oncology, CHU Toulouse, H\u00f4pital Larrey, 31400 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Huchot","sequence":"additional","affiliation":[{"name":"Departement of Pneumology, CH La Reunion, 97400 Saint Pierre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3459-2767","authenticated-orcid":false,"given":"Lionel","family":"Falchero","sequence":"additional","affiliation":[{"name":"Department of Pneumology, H\u00f4pital Nord-Ouest, 69653 Villefranche-sur-Sa\u00f4ne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Doubre","sequence":"additional","affiliation":[{"name":"Thoracic Oncology, Hopital Foch, 40, Rue Worth, 92150 Suresnes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-0969","authenticated-orcid":false,"given":"Olivier","family":"Bylicki","sequence":"additional","affiliation":[{"name":"Department of Pneumology, H\u00f4pital d\u2019Instruction des Arm\u00e9es Saint-Anne, Boulevard Sainte-Anne, 83100 Toulon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4290-5524","authenticated-orcid":false,"given":"Christos","family":"Choua\u00efd","sequence":"additional","affiliation":[{"name":"Department of Pneumology, Centre Hospitalier Intercommunal de Cr\u00e9teil, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5807-9503","authenticated-orcid":false,"given":"Laurent","family":"Greillier","sequence":"additional","affiliation":[{"name":"Multidisciplinary Oncology and Therapeutic Innovations, APHM, INSERM, CNRS, CRCM, H\u00f4pital Nord, Aix\u2013Marseille Universit\u00e9, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.annonc.2022.12.013","article-title":"Non-oncogene-addicted 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