Randomized Phase II Trial of Docetaxel Plus Cetuximab or Docetaxel Plus Bortezomib in Patients With Advanced Non–Small-Cell Lung Cancer and a Performance Status of 2: CALGB 30402

Abstract

PurposeA randomized phase II trial of two novel treatment strategies in the first-line management of advanced non–small-cell lung cancer patients with performance status (PS) 2.Patients and MethodsPatients were assigned to docetaxel 30 mg/m2on days 1, 8, and 15 every 28 days in combination with either cetuximab 400 mg/m2loading dose followed by 250 mg/m2weekly (D + C) or bortezomib 1.6 mg/m2on days 1, 8, and 15 every 28 days (D + B) for up to 4 cycles. Patients with responding or stable disease continued cetuximab or bortezomib until progression. The primary end point was progression-free survival (PFS) rate at 6 months.ResultsSixty-four patients were enrolled and 59 were included in this analysis. Complete or partial response rates were 13.3% and 10.3% for D + C and D + B, respectively. Median PFS was 3.4 months in the D + C arm and 1.9 months in the D + B arm. Corresponding figures for 6-month PFS were 27.8% and 13.8% and 5.0 and 3.9 months for median survival, respectively. Grade 3/4 hematologic toxicity was 16% for D + C and 21% for D + B, whereas nonhematologic toxicities were observed in 63% and 44% of patients, respectively. There was one treatment-related death in each arm.ConclusionThese results confirm the poor prognosis associated with a PS of 2 and the difficulty in translating recent advances in targeted therapy to this subset of patients. While the results in the D + C arm are numerically superior, neither combination met the prespecified PFS end point to justify further research in this setting.

Incidence and risk of severe infections associated with anti-epidermal growth factor receptor monoclonal antibodies in cancer patients: a systematic review and meta-analysis

“…According to the inclusion criteria of each trial, patients were required to have adequate hepatic, renal and hematological function. Underlying malignancies included colorectal cancer (eleven trials) [14,15,[22][23][24][25][26][27][28][29][30][31], non-small-cell lung cancer (seven trials) [32][33][34][35][36][37][38], head and neck cancer (four trials) [5,13,39,40], breast cancer (one trial) [41], urothelial carcinoma (one trial) [42], pancreatic cancer (one trial) [43] and esophagogastric cancer (one trial) [44].…”

Cetuximab and Other Anti–Epidermal Growth Factor Receptor Monoclonal Antibodies in the Treatment of Non-Small Cell Lung Cancer

“…These disappointing results confirm the poor prognosis associated with PS 2 patients. Neither combination produced data to justify further research in this subset of patients [29]. Table 2 summarizes the results of randomized trials with cetuximab in the treatment of advanced NSCLC.…”

Phase 2 study of frontline bortezomib in patients with advanced non-small cell lung cancer

“…In 80 patients with Karnofsky performance status >70%, response rates to docetaxel and bortezomib was 9%, disease control rates was 54%, median time to progression was 4.0 months and median survival was 7.8 months [13]. In performance status 2 patients, weekly docetaxel and bortezomib provided a similar range of response rate (10.3%), median PFS and OS were 1.9 and 3.9 months, reflecting in part the poor prognosis of these patients [22]. In a randomized phase II study, pemetrexed (500 mg/m 2 ) on day 1 plus bortezomib (1.6 mg/m 2 ) on days 1 and 8 were compared to pemetrexed alone [17].…”