Details

Autor(en) / Beteiligte

• Mazieres, Julien
• Lafitte, Claire
• Ricordel, Charles
• Greillier, Laurent
• Negre, Elodie
• Zalcman, Gérard
• Domblides, Charlotte
• Madelaine, Jeannick
• Bennouna, Jaafar
• Mascaux, Céline
• Moro-Sibilot, Denis
• Pinquie, François
• Cortot, Alexis B
• Otto, Josiane
• Cadranel, Jacques
• Langlais, Alexandra
• Morin, Franck
• Westeel, Virginie
• Besse, Benjamin

Titel

Combination of Trastuzumab, Pertuzumab, and Docetaxel in Patients With Advanced Non-Small-Cell Lung Cancer Harboring HER2 Mutations: Results From the IFCT-1703 R2D2 Trial

Ist Teil von

• Journal of clinical oncology, 2022-03, Vol.40 (7), p.719-728

Ort / Verlag

United States: American Society of Clinical Oncology

Erscheinungsjahr

2022

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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. The IFCT 1703-R2D2 trial is a multicenter, nonrandomized phase II study. Patients with -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/m 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). 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%). Triple therapy with trastuzumab, pertuzumab, and docetaxel is feasible and effective for -mutated pretreated advanced NSCLC. These results highlight the effectiveness of the HER2 antibody-based strategy, which should be considered for these patients.