A phase II open-label clinical study of comparing nab-paclitaxel with pemetrexed as second-line chemotherapy for patients with stage IIIB/IV non-small-cell lung cancer

Abstract

Current choices of second-line chemotherapy regimens for patients with advanced non-small-cell lung cancer (NSCLC) are extremely limited. We applied a new strategy of using nab-paclitaxel as single chemotherapy regimen in second-line setting for patients with unsuccessful first-line chemotherapy. The efficacy and safety were compared with patients who received standard second-line regimen pemetrexed. Patients with stage IIIB/IV NSCLC and unsuccessful first-line platinum-based chemotherapy were randomly divided into two arms. Arm I received pemetrexed 500 mg/m(2) intravenously (i.v.) on day 1 of 3-week cycle. Arm II received nab-paclitaxel 150 mg/m(2) i.v. on days 1 and 8 of 3-week cycle. The primary endpoint was overall survival (OS). One hundred and eleven patients were randomly assigned to receive pemetrexed (n = 56) and nab-paclitaxel (n = 55). Median OSs were 9.4 months (95% CI 7.1-12.5 months) for pemetrexed and 9.9 months (95% CI 8.2-11.9 months) for nab-paclitaxel. Median PFS was 4.6 months (95% CI 2.7-6.1 months) for pemetrexed and 5.1 months (95% CI 3.9-7.4 months) for nab-paclitaxel. While no CR was reported for either treatment, PRs + SDs were seen in 32/56 (57.1%) patients in pemetrexed arm and 36/55 (65.5%) patients in nab-paclitaxel arm. Grade 3 and grade 4 adverse events were comparable between two treatment arms. New second-line chemotherapy single-regimen nab-paclitaxel showed equivalent efficacy and toxicity profiles as pemetrexed in treating patients with NSCLC.

Treatment of recurrent and platinum-refractory stage IV non-small cell lung cancer with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as a single agent

“…Patients in our study tolerated nab -paclitaxel well as salvage therapy, consistent with other reports showing a favorable toxicity profile for the drug as a single agent[8, 14-16, 25]. A phase I/II trial by Rizvi et al of nab -paclitaxel given weekly at 125mg/m 2 for the front-line treatment of advanced NSCLC reported neutropenia, leukopenia, sensory neuropathy, and fatigue as the most common grade 3/4 toxicities[10].…”

“…The ORR in the nab-paclitaxel arm was 14.5% with a disease control rate of 65.5%. The median PFS was 5.1 months for nab-paclitaxel and 4.6 months for pemetrexed, with the difference not being statistically significant[16]. Together these data as well as those presented in our study provide evidence for the efficacy of nab -paclitaxel beyond front-line therapy in advanced NSCLC and suggest that Eastern and Western populations may respond similarly to the drug in this setting.…”

“…A study by Green et al using 260mg/m 2 of nab -paclitaxel every 21 days also reported similar grade 3 toxicities, as well as a small percentage of grade 3 arthralgias[8]. The main grade 3 or 4 toxicities reported in the retrospective study by Xing et al also included neutropenia, peripheral neuropathy, myalgias/arthralgias, and fatigue[14], while the prospective trials done in China reported dizziness, fatigue, pulmonary embolism, nausea, fever, anemia, and thrombocytopenia as the most commonly seen grade 3 or 4 adverse events[15, 16]. Twenty-six percent of the patients in our study required dose adjustment because of toxicity, mostly grade 2/3 fatigue and grade 2 peripheral sensory neuropathy.…”

“…While several studies have examined the efficacy of nab -paclitaxel for the initial management of advanced NSCLC, studies on the use of this drug as a single agent in the second-line setting and beyond have predominantly been done in East Asia[14-16]. Limited data therefore exists for nab -paclitaxel when used as a single agent in later lines of therapy in Western populations.…”

A randomized placebo-controlled clinical study of nab-paclitaxel as second-line chemotherapy for patients with advanced non-small cell lung cancer in China

“…on days 1, 8 and 15 of a 28-day cycle. Liu et al [19] compared the median PFS of patients with advanced NSCLC after unsuccessful first-line chemotherapy and the results showed that the nab -paclitaxel had better PFS (5.1 months) than pemetrexed (4.6 months). Similarly, our study also showed that the nab -paclitaxel had good efficacy in PFS (4.6 months).…”