Docetaxel-carboplatin in combination with erlotinib and/or bevacizumab in patients with non-small cell lung cancer

Abstract

BackgroundBevacizumab and erlotinib have been demonstrated to prolong overall survival in patients with non-squamous non-small cell lung cancer (NSCLC). We designed a four-arm Phase III trial to evaluate the efficacy and toxicity of the combination of docetaxel, carboplatin, bevacizumab, and erlotinib in the first-line treatment of patients with NSCLC.MethodsA total of 229 patients with stage IIIb/IV non-squamous NSCLC were treated with two cycles of carboplatin (area under the concentration-time curve 5.5) and docetaxel 100 mg/m2 as chemotherapy. After completion of two treatment cycles, patients were evaluated for response and divided into four groups: 61/229 continued with four more cycles of chemotherapy (control group), 52/229 received chemotherapy plus erlotinib 150 mg daily, 56/229 received chemotherapy plus bevacizumab 7.5 mg/kg, and 60/229 were treated with the combination of chemotherapy, erlotinib, and bevacizumab until disease progression. The primary endpoint was overall survival.ResultsOver 4 years of follow-up, there was no statistically significant difference in survival and time to progression between the four treatment groups. After two cycles of chemotherapy, responders and nonresponders were divided according to their response in order to examine the role of initial response as an independent factor in survival and response when a biological agent is combined with chemotherapy. Nonresponders, who received additional therapy with bevacizumab or combination therapy, had a survival benefit [657 days (95% confidence interval 349–970) and 681 days (95% confidence interval 315–912), respectively], which was statistically significant compared with continuation of cytotoxic chemotherapy (P < 0.001). The combination therapy had a safety profile comparable with that of bevacizumab and erlotinib taken individually.ConclusionAdministration of bevacizumab and erlotinib in combination with first-line chemotherapy, followed by bevacizumab and erlotinib monotherapy as maintenance, showed promising results in patients with NSCLC, with reduced toxicity as compared with chemotherapy alone, but did not translate into longer overall survival.

Phase II study of carboplatin, docetaxel and bevacizumab for chemotherapy-naïve patients with advanced non-squamous non-small cell lung cancer

“…To expand the clinical utility of bevacizumab in front-line treatment of patients with non-squamous NSCLC, a variety of combinations have been reported with promising results. These combinations include regimens with oxaliplatin [31][32][33] as a platinum agent, vinorelbine [34], docetaxel [33,[35][36][37], pemetrexed [32,[38][39][40][41], nanoparticle albumin-bound paclitaxel [42], oral S-1 [43,44], and ixabepilone [40]. The present study provided further evidence of the high efficacy of a 3-drug combination chemotherapy including bevacizumab for the treatment of advanced nonsquamous NSCLC.…”

Current status of research and treatment for non-small cell lung cancer in never-smoking females

“…NSCLC accounts for 80% of all lung cancers 5 and NSCLC patients have a poor prognosis. The 3 main types of NSCLC include adenocarcinoma (including BAC, Bronchioloalveolar cancer) in 32-40% of cases, squamous in 25-30% of cases, and large cell in 8-16% of cases.…”

“…The 3 main types of NSCLC include adenocarcinoma (including BAC, Bronchioloalveolar cancer) in 32-40% of cases, squamous in 25-30% of cases, and large cell in 8-16% of cases. 5 Irrespective of histological and lung cancer subtypes, NSCLC patients show metastasis to these major sites: liver (33-40%); brain (15-43%), kidney (16-23%), adrenal glands (18-38%), bone (19-33%), and abdominal lymph nodes (29%). 18,19 It is important to consider that agents used to treat primary tumors may not always display efficacy toward metastatic lesions with secondary mutations, and some metastatic locations (i.e.…”

“…74 Surgery is the best curative therapeutic approach in the early respectable stages. 5,75 However, even in stage I patients, the mean 5-year overall survival rate (OS) is less than 70%. 76 Patients with lung carcinoma have a poor prognosis because most have disease recurrence after complete surgical resection.…”

“…At the time of diagnosis, about 75% of NSCLC patients present with a locally advanced or metastatic disease. 3 NSCLC accounts for 80% of all lung cancers 5 and these patients have a poor prognosis. Squamous cell carcinoma and adenocarcinoma are 2 main types of NSCLC.…”