Safety, resource use, and quality of life in paramount: a phase III study of maintenance pemetrexed versus placebo after induction pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer.

Abstract

INTRODUCTION:

In a phase III, randomized, double-blind study (PARAMOUNT), maintenance pemetrexed demonstrated significant benefit in advanced non-small-cell lung cancer (NSCLC). We present safety, resource use, and quality of life (QoL) results.

METHODS:

After four 21-day cycles of pemetrexed-cisplatin (N = 939), patients with advanced nonsquamous NSCLC, whose disease had not progressed and who had a performance status of 0/1, were randomized 2:1 (N = 539) to maintenance pemetrexed 500 mg/m plus best supportive care or placebo plus best supportive care every 21 days until disease progression or unacceptable toxicity. QoL was measured using the EuroQol 5-dimensional questionnaire (EQ-5D).

RESULTS:

Frequently reported grade 3 to 4 drug-related toxicities with maintenance pemetrexed versus placebo were anemia (4.5% versus 0.6%; p = 0.016), fatigue (4.2% versus 0.6%; p = 0.016), and neutropenia (3.6% versus 0.0%; p < 0.006). No significant differences in drug-related grade 3 to 5 toxicities were observed with long-term pemetrexed exposure (>6 cycles), except grade 3 to 4 neutropenia, which did not result in increased infections. Patients on maintenance pemetrexed required more transfusions (13.4% versus 5.0%; p = 0.003), granulocyte colony- or granulocyte-macrophage colony-stimulating factors (5.3% versus 0.0%; p <0.001), anti-infectives (25.3% versus 16.7%; p = 0.028), and hospitalizations because of study drug (8.4% versus 3.3%, p = 0.028) than placebo-treated patients did. No significant treatment-by-time interactions, overall treatment differences, or clinically relevant changes from baseline were observed in EQ-5D scores during treatment.

CONCLUSIONS:

Long-term use of continuation maintenance pemetrexed was well tolerated; resource use was low, corresponding with known pemetrexed toxicities. The EQ-5D results demonstrate that patients tolerate long-term maintenance pemetrexed without worsening QoL.

• Authors: Cesare Gridelli, Filippo de Marinis, Jean-Louis Pujol, Martin Reck, Rodryg Ramlau, Barbara Parente, Thierry Pieters, Gary Middleton, Jesus Corral, Katherine Winfree, Symantha Melemed, Anna Zimmermann, William John, Julie Beyrer, Nadia Chouaki, Carla Visseren-Grul, Luis G Paz-Ares
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 7 Issue 11 Pg. 1713-21 (Nov 2012) ISSN: 1556-1380 [Electronic] United States
• PMID: 23059776 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamates
• Pemetrexed
• Guanine
• Cisplatin

Topics

• Adenocarcinoma (drug therapy, mortality, pathology)
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality, pathology)
• Cisplatin (administration & dosage)
• Disease Management
• Double-Blind Method
• Female
• Follow-Up Studies
• Glutamates (administration & dosage)
• Guanine (administration & dosage, analogs & derivatives)
• Health Resources
• Humans
• Lung Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Pemetrexed
• Prognosis
• Quality of Life
• Remission Induction
• Survival Rate