Julien Mazieres1, Claire Lafitte2, Charles Ricordel3, Laurent Greillier4, Elodie Negre5, Gérard Zalcman6, Charlotte Domblides7, Jeannick Madelaine8, Jaafar Bennouna9, Céline Mascaux10, Denis Moro-Sibilot11, François Pinquie12, Alexis B Cortot13, Josiane Otto14, Jacques Cadranel15, Alexandra Langlais16, Franck Morin17, Virginie Westeel18, Benjamin Besse19. 1. Pneumology, CHU Toulouse-Hôpital Larrey, Université Paul Sabatier, Toulouse, France. 2. Pneumology, Hôpital Cardio-Vasculaire & Pneumologique Louis Pradel, Bron, France. 3. Pneumology, CHU Rennes-Hôpital Pontchaillou, Rennes, France. 4. Aix Marseille Univ, APHM, INSERM, CNRS, CRCM, Hôpital Nord, Multidisciplinary Oncology and Therapeutic Innovations, Marseille, France. 5. Thoracic Oncology, Hôpital Arnaud de Villeneuve, Montpellier, France. 6. Thoracic Oncology, CIC INSERM 1425, Université de Paris, Hôpital Bichat, Paris, France. 7. Medical Oncology, CHU de Bordeaux, Hôpital Saint André, Bordeaux, France. 8. Pneumology, CHU Côte de Nacre, Caen, France. 9. Medical Oncology-CHU de Nantes, CRCINA INSERM, Nantes, France. 10. Pneumology, Nouvel Hôpital Civil-Hôpitaux Universitaires de Strasbourg, Inserm UMR_S 1113, IRFAC, Strasbourg University, Strasbourg, France. 11. Pneumology, CHU Grenoble, Grenoble, France. 12. Pneumology, Centre Hospitalier du Mans, Le Mans, France. 13. Univ. Lille, CHU Lille, Thoracic Oncology Department, CNRS, Inserm, Institut Pasteur de Lille, UMR9020-UMR-S 1277-Canther, F-59000, Lille, France. 14. Oncology, Centre Antoine Lacassagne, Nice, France. 15. Pneumology and Thoracic Oncology, Hôpital Tenon, Paris, France. 16. Biostatistics, Intergroupe Francophone de Cancérologie Thoracique, Paris, France. 17. Clinical Research Unit, Intergroupe Francophone de Cancérologie Thoracique, Paris, France. 18. Pneumology, Hopital Jean Minjoz, Besançon, France. 19. Medicine and Thoracic Pathology Committee, Gustave Roussy, Villejuif, France; Paris-Saclay University, Orsay, France.
Abstract
PURPOSE: HER2 exon 20 insertions and point mutations are oncogenic drivers found in 1%-2% of patients with non-small-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. METHODS: The IFCT 1703-R2D2 trial is a multicenter, nonrandomized phase II study. Patients with HER2-mutated, advanced NSCLC who progressed after ≥ 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/m2 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). RESULTS: 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 ≥ 3 treatment-related adverse events were neutropenia (33%), diarrhea (13%), and anemia (9%). CONCLUSION: 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.
PURPOSE: HER2 exon 20 insertions and point mutations are oncogenic drivers found in 1%-2% of patients with non-small-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. METHODS: The IFCT 1703-R2D2 trial is a multicenter, nonrandomized phase II study. Patients with HER2-mutated, advanced NSCLC who progressed after ≥ 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/m2 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). RESULTS: 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 ≥ 3 treatment-related adverse events were neutropenia (33%), diarrhea (13%), and anemia (9%). CONCLUSION: 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.
Authors: Bob T Li; Egbert F Smit; Yasushi Goto; Kazuhiko Nakagawa; Hibiki Udagawa; Julien Mazières; Misako Nagasaka; Lyudmila Bazhenova; Andreas N Saltos; Enriqueta Felip; Jose M Pacheco; Maurice Pérol; Luis Paz-Ares; Kapil Saxena; Ryota Shiga; Yingkai Cheng; Suddhasatta Acharyya; Patrik Vitazka; Javad Shahidi; David Planchard; Pasi A Jänne Journal: N Engl J Med Date: 2021-09-18 Impact factor: 176.079