Randomized phase 2b study of pralatrexate versus erlotinib in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) after failure of prior platinum-based therapy Journal Article
| Authors: | Kelly, K.; Azzoli, C. G.; Zatloukal, P.; Albert, I.; Jiang, P. Y. Z.; Bodkin, D.; Pereira, J. R.; Juhász, E.; Iannotti, N. O.; Weems, G.; Koutsoukos, T.; Patel, J. D. |
| Article Title: | Randomized phase 2b study of pralatrexate versus erlotinib in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) after failure of prior platinum-based therapy |
| Abstract: | INTRODUCTION:: Pralatrexate, a folate analogue targeting dihydrofolate reductase, has antitumor activity in non-small-cell lung cancer (NSCLC). This randomized phase 2b trial was designed to further evaluate pralatrexate activity in NSCLC by estimating overall survival (OS) relative to erlotinib in patients with relapsed/refractory disease. METHODS:: In 43 centers across 6 countries, patients were randomized 1:1 to receive intravenous pralatrexate 190 mg/m on days 1 and 15 of a 28-day cycle, or oral erlotinib 150 mg/day. The primary objective was to estimate OS in all patients and prespecified subgroups using relative comparisons of hazard ratios (HRs). Secondary endpoints included progression-free survival, response rate, and safety. Key eligibility criteria included: (1) ≥1 prior platinum-based therapy, (2) Eastern Cooperative Oncology Group performance status of 0 to 1, and 3) a smoking history of 100 cigarettes or more. RESULTS:: A total of 201 patients were randomized. A trend toward improvement in OS favoring pralatrexate was observed with an HR of 0.84 (95% confidence interval: 0.61-1.14) in the intent-to-treat population. This favorable survival result was seen in most prespecified subgroups for pralatrexate. The largest reduction in the risk of death was observed in patients with nonsquamous cell carcinoma (n = 107; HR = 0.65; 95% confidence interval: 0.42-1.0). The most common grade 3 to 4 adverse event in the pralatrexate arm was mucositis (23%). Discontinuation of pralatrexate for any grade of mucositis was 21%. CONCLUSIONS:: Pralatrexate demonstrated a trend toward improved survival relative to erlotinib in patients with advanced NSCLC. Future studies should include a mucositis management plan to improve tolerability and maximize treatment benefit. Copyright © 2012 by the International Association for the Study of Lung Cancer. |
| Keywords: | survival; adult; cancer chemotherapy; cancer survival; controlled study; human tissue; aged; aged, 80 and over; disease-free survival; middle aged; survival rate; treatment failure; retrospective studies; major clinical study; overall survival; histopathology; neutropenia; erlotinib; diarrhea; drug dose reduction; drug safety; drug withdrawal; united states; cancer staging; follow-up studies; neoplasm staging; progression free survival; drug eruption; multiple cycle treatment; phase 2 clinical trial; anemia; lung non small cell cancer; mucosa inflammation; randomized controlled trial; stomatitis; thrombocytopenia; carcinoma, non-small-cell lung; lung neoplasms; clinical protocol; receptor, epidermal growth factor; dose-response relationship, drug; drug dose escalation; dyspnea; protein kinase inhibitors; multicenter study; drug response; cancer fatigue; cancer relapse; platinum; platinum derivative; folic acid; folic acid antagonists; drug dose regimen; drug treatment failure; quinazolines; pralatrexate; aminopterin; cyanocobalamin; antifolate; nonsmall-cell lung cancer |
| Journal Title: | Journal of Thoracic Oncology |
| Volume: | 7 |
| Issue: | 6 |
| ISSN: | 1556-0864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2012-06-01 |
| Start Page: | 1041 |
| End Page: | 1048 |
| Language: | English |
| DOI: | 10.1097/JTO.0b013e31824cc66c |
| PROVIDER: | scopus |
| PUBMED: | 22534814 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 June 2012" - "Source: Scopus" |
