Phase I/II study of erlotinib, carboplatin, pemetrexed, and bevacizumab in chemotherapy-naïve patients with advanced non-squamous non-small cell lung cancer harboring epidermal growth factor receptor mutation

Abstract

Background Epidermal growth factor receptor tyrosine kinase inhibitors significantly prolong the progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC). However, most patients develop tumor regrowth and their prognosis remains poor. A new treatment strategy for NSCLC harboring EGFR mutation is therefore necessary. Methods In phase I, eligible patients were administered oral erlotinib daily and intravenous pemetrexed, carboplatin, and bevacizumab every 3 weeks for four cycles with maintenance of pemetrexed and bevacizumab until progressive disease was observed. The dose of erlotinib was 100 mg for dose level 1 and 150 mg for dose level 2. The doses of pemetrexed, carboplatin, and bevacizumab were fixed at 500 mg/m 2 , area under the concentration–time curve of 6 mg/mL · min, and 15 mg/kg, respectively. The dose-limiting toxicities were grade 3/4 neutropenia with fever or infection, grade 4 leukopenia lasting for ≥7 days, grade 4 thrombocytopenia, grade 3/4 uncontrollable nonhematological toxicity, and delayed administration of the subsequent cycle by >2 weeks because of adverse events. Results Six patients were enrolled in phase I (dose level 1, n = 3; dose level 2, n = 3). During the induction phase, grade 3 neutropenia without fever was observed in one patient at dose level 1 and two patients at dose level 2. Grade 3 anemia was reported in one patient at dose level 1 and grade 3 thrombocytopenia was reported in two patients at dose level 1 and dose level 2, respectively. Conclusion Four-drug combination therapy is a feasible and promising.

Efficacy and Safety of Neoadjuvant Targeted Therapy vs. Neoadjuvant Chemotherapy for Stage IIIA EGFR-Mutant Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…Our research found that the EGFR mutation-positive stage IIIA NSCLC patients are extremely sensitive to the NTT strategy, meanwhile, the incidence of grade 3/4 AEs in the NTT group was significantly lower than that of NCT. Consistent with previous reported results, the main adverse event of NTT is skin rash, and the main adverse events of NCT are myelosuppression and gastrointestinal reaction ( 22 ). In clinical practice, the toxicity associated with myelosuppression may be ignored by patients because it has no direct symptoms in the early stage ( 23 ).…”

Neoadjuvant Four-Drug Combination Therapy for NSCLC With EGFR Mutation Avoiding Total Pneumonectomy

“…However, despite achieving significant downstaging of tumors, local or distant disease relapsed in less than 1 year. Various combination therapy achieved the promising results in the setting of advanced stage, including chemotherapy/EGFR-TKI ( 3 , 4 ), chemotherapy/Bevacizumab ( 5 ), EGFR-TKI/Bevacizumab ( 6 , 7 ), and eventually chemotherapy/EGFR-TKI/Bevacizumab ( 8 ). Currently, some prospective trials ( 9 – 11 ) had investigated the critical role of EGFR-TKI (gefitinib or erlotinib) in neoadjuvant therapy, the objective response rate (ORR) was ranged from 42.1 to 54.5%, and the rate of major pathological regression (MPR) was from 9.7% up to 24.2%.…”

Erlotinib combined with bevacizumab and chemotherapy in first line osimertinib-resistant NSCLC patient with leptomeningeal metastasis

“…Although the first- and second- generation EGFR TKIs are active for EGFR C797S and SM, the patient inevitably undergo development of the EGFR SM/C797S/T790M triple mutations [18] . Now, the promising results of various combination therapy are coming out, including TKI plus chemotherapy, [19,20] TKI plus bevacizumab, [10] bevacizumab plus chemotherapy, [21] and eventually TKI plus bevacizumab and chemotherapy [22] . A neoadjuvant 4-agent combination therapy, icotinib plus carboplatin, pemetrexed and bevacizumab, for locally advanced non-squamous NSCLC patient harboring EGFR mutations avoiding total pneumonectomy were reported [23] .…”