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.

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.