{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T11:22:30Z","timestamp":1792408950871,"version":"4.4.0"},"reference-count":27,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>HER2 exon 20 insertions and point mutations are oncogenic drivers found in 1%-2% of patients with non\u2013small-cell lung cancer (NSCLC). No targeted therapy is approved for this subset of patients. We prospectively evaluated the effectiveness of the combination of two antibodies against human epidermal growth factor 2 (HER2 [HER2] trastuzumab and pertuzumab with docetaxel; trastuzumab and pertuzumab) and docetaxel.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      The IFCT 1703-R2D2 trial is a multicenter, nonrandomized phase II study. Patients with HER2-mutated, advanced NSCLC who progressed after \u2265 1 platinum-based treatment were enrolled. Patients received pertuzumab at a loading dose of 840 mg and 420 mg thereafter; trastuzumab at an 8 mg\/kg loading dose and 6 mg\/kg thereafter; and docetaxel at a dose of 75 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      every 3 weeks. The primary outcome was the objective response rate (ORR). Other end points included the duration of response, progression-free survival, and safety ( NCT03845270 ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Forty-five patients were enrolled and treated. The median age was 64.5 years (range, 31-84 years), 35% were smokers, 72% were females, 15% had an Eastern Cooperative Oncology Group performance status of 2, and 30% had brain metastases. The objective response rate was 29% (n = 13), and 58% had stable disease (n = 26). The median progression-free survival was 6.8 months (95% CI, 4.0 to 8.5). The median duration of response in patients with a confirmed response (n = 13) was 11 months (95% CI, 2.9 to 14.9). Grade 3\/4 treatment-related adverse events were observed in 64% of the patients. No patient discontinued treatment because of toxicity. The most frequent grade \u2265 3 treatment-related adverse events were neutropenia (33%), diarrhea (13%), and anemia (9%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Triple therapy with trastuzumab, pertuzumab, and docetaxel is feasible and effective for HER2-mutated pretreated advanced NSCLC. These results highlight the effectiveness of the HER2 antibody-based strategy, which should be considered for these patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.21.01455","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T15:59:32Z","timestamp":1643039972000},"page":"719-728","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":70,"title":["Combination of Trastuzumab, Pertuzumab, and Docetaxel in Patients With Advanced Non\u2013Small-Cell Lung Cancer Harboring\n                    <i>HER2<\/i>\n                    Mutations: Results From the IFCT-1703 R2D2 Trial"],"prefix":"10.1200","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5921-7613","authenticated-orcid":false,"given":"Julien","family":"Mazieres","sequence":"first","affiliation":[{"name":"Pneumology, CHU Toulouse\u2014H\u00f4pital Larrey, Universit\u00e9 Paul Sabatier, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Lafitte","sequence":"additional","affiliation":[{"name":"Pneumology, H\u00f4pital Cardio-Vasculaire & Pneumologique Louis Pradel, Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Ricordel","sequence":"additional","affiliation":[{"name":"Pneumology, CHU Rennes\u2014H\u00f4pital Pontchaillou, Rennes, 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":"Aix Marseille Univ, APHM, INSERM, CNRS, CRCM, H\u00f4pital Nord, Multidisciplinary Oncology and Therapeutic Innovations, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Negre","sequence":"additional","affiliation":[{"name":"Thoracic Oncology, H\u00f4pital Arnaud de Villeneuve, Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0343-9575","authenticated-orcid":false,"given":"G\u00e9rard","family":"Zalcman","sequence":"additional","affiliation":[{"name":"Thoracic Oncology, CIC INSERM 1425, Universit\u00e9 de Paris, H\u00f4pital Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9455-0657","authenticated-orcid":false,"given":"Charlotte","family":"Domblides","sequence":"additional","affiliation":[{"name":"Medical Oncology, CHU de Bordeaux, H\u00f4pital Saint Andr\u00e9, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannick","family":"Madelaine","sequence":"additional","affiliation":[{"name":"Pneumology, CHU C\u00f4te de Nacre, Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaafar","family":"Bennouna","sequence":"additional","affiliation":[{"name":"Medical Oncology\u2014CHU de Nantes, CRCINA INSERM, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1846-2807","authenticated-orcid":false,"given":"C\u00e9line","family":"Mascaux","sequence":"additional","affiliation":[{"name":"Pneumology, Nouvel H\u00f4pital Civil\u2014H\u00f4pitaux Universitaires de Strasbourg, Inserm UMR_S 1113, IRFAC, Strasbourg University, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6776-8610","authenticated-orcid":false,"given":"Denis","family":"Moro-Sibilot","sequence":"additional","affiliation":[{"name":"Pneumology, CHU Grenoble, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Pinquie","sequence":"additional","affiliation":[{"name":"Pneumology, Centre Hospitalier du Mans, Le Mans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0098-2238","authenticated-orcid":false,"given":"Alexis B.","family":"Cortot","sequence":"additional","affiliation":[{"name":"Univ. Lille, CHU Lille, Thoracic Oncology Department, CNRS, Inserm, Institut Pasteur de Lille, UMR9020\u2014UMR-S 1277\u2014Canther, F-59000, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josiane","family":"Otto","sequence":"additional","affiliation":[{"name":"Oncology, Centre Antoine Lacassagne, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Cadranel","sequence":"additional","affiliation":[{"name":"Pneumology and Thoracic Oncology, H\u00f4pital Tenon, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0774-8762","authenticated-orcid":false,"given":"Alexandra","family":"Langlais","sequence":"additional","affiliation":[{"name":"Biostatistics, Intergroupe Francophone de Canc\u00e9rologie Thoracique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7510-2787","authenticated-orcid":false,"given":"Franck","family":"Morin","sequence":"additional","affiliation":[{"name":"Clinical Research Unit, Intergroupe Francophone de Canc\u00e9rologie Thoracique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2358-3694","authenticated-orcid":false,"given":"Virginie","family":"Westeel","sequence":"additional","affiliation":[{"name":"Pneumology, Hopital Jean Minjoz, Besan\u00e7on, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5090-8189","authenticated-orcid":false,"given":"Benjamin","family":"Besse","sequence":"additional","affiliation":[{"name":"Medicine and Thoracic Pathology Committee, Gustave Roussy, Villejuif, France; 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