P3.02b-050 A Phase I/II Study of Erlotinib, Carboplatin, Pemetrexed and Bevacizumab for Advanced Non-Squamous NSCLC Harboring EGFR Mutation: Topic: EGFR Clinical

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) drastically prolonged progression free survival (PFS) of patients with non-squamous non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, most cases show tumor regrowth after approximately only ten months treatment, and the prognosis is still poor. Then it is necessary to make new strategy of treatment for NSCLC harboring EGFR mutation, and we designed phase I/II study of Erlotinib, Carboplatin, Pemetrexed and Bevacizumab in chemotherapy-naïve patients with EGFR mutation positive advanced non-squamous NSCLC. In the phase I part, eligible patients were administrated orally Erlotinib daily, and Pemetrexed, Carboplatin and Bevacizumab intravenously every three weeks for four cycles with maintenance of Pemetrexed and Bevacizumab until PD. The dose level of Erlotinib were 100mg in level 1 and 150mg in level 2. And the dose of pemetrexed, carboplatin and bevacizmab were fixed as 500mg per m2, AUC6 and 15mg per kg. The dose limiting toxicities are Grade (Gr) 3-4 neutropenia with fever or infection, Gr 4 leukopenia lasting for 7 days or longer, Gr 4 thrombocytopenia, Gr 3-4 uncontrollable non-hematological toxicity and delayed administration of the subsequent course by more than 2 weeks due to adverse events. Six patients were enrolled in Phase I part (level 1-three, level 2-three). The median age was 71.5 y.o. (Range, 46-76 y.o). Male was one and female were five. Histology of all patients was adenocarcinoma, and Ex19del was four and Ex21 L858R was two. A Gr3 of neutropenia without fever was observed in level 1, and a Gr3 of neutropenia without fever, three Gr3 thrombocytopenia and a stomatitis were observed in level 2(Table1). No DLT events were observed in Phase I.Table 1Grade123ANC11PLT2Anemia2Stomatitis11Nausea12Appetite loss12Rash1Transaminase1T.Bil1Fatigue1Bleeding1Diarrhea1 Open table in a new tab The recommend dose of Erlotinb is 150mg daily.