Jean-Louis Pujol1, Luis Paz-Ares2, Filippo de Marinis3, Mircea Dediu4, Michael Thomas5, Paolo Bidoli6, Jesus Corral2, Belen San Antonio7, Nadia Chouaki8, William John9, Annamaria Zimmermann9, Carla Visseren-Grul10, Cesare Gridelli11. 1. Montpellier University Hospital, Montpellier, France. Electronic address: jl-pujol@chu-montpellier.fr. 2. Instituto de Biomedicina de Sevilla - IBIS (Hospital Universitario Virgen del Rocío, Universidad de Sevilla and Consejo Superior de Investigaciones Científicas), Seville, Spain. 3. San Camillo, High Specialization Hospital, Rome, Italy; Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy. 4. Institute of Oncology Bucharest, Bucharest, Romania. 5. Internistische Onkologie der Thoraxtumoren, Thoraxklinik im Universitätsklinikum Heidelberg, Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research, Heidelberg, Germany. 6. Az Ospedale S. Gerardo, Monza, Italy. 7. Eli Lilly and Company, Madrid, Spain. 8. Eli Lilly and Company, Neuilly sur Seine, France. 9. Eli Lilly and Company, Indianapolis. 10. Eli Lilly Oncology Europe, Houten, The Netherlands. 11. Division of Medical Oncology, S. G. Moscati Hospital, Avellino, Italy.
Abstract
INTRODUCTION: In the PARAMOUNT ("A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance Pemetrexed plus Best Supportive Care vs. Best Supportive Care Immediately Following Induction Treatment with Pemetrexed Plus Cisplatin for Advanced Non-Squamous Non-Small-Cell Lung Cancer") trial, patients with advanced nonsquamous non-small-cell lung cancer (NS-NSCLC) benefited from pemetrexed maintenance therapy after induction therapy withpemetrexed and cisplatin by extending survival, delaying disease progression, and maintaining quality of life (QoL). However, low-grade 1 or 2 toxicities during long-term maintenance treatment may become burdensome and impact QoL. MATERIALS AND METHODS:Patients in this double-blind study (n = 539), who had completed 4 induction cycles (pemetrexed with cisplatin) without progressive disease (PD) and had an ECOG performance status of 0/1, were randomized 2:1 to pemetrexed maintenance (500 mg/m(2), day 1) plus best supportive care (BSC) or placebo plus BSC until PD. Adverse events (by maximum Common Terminology Criteria for Adverse Events [CTCAE] grade) and QoL (EuroQol 5-dimensional [EQ-5D] scale) were assessed. RESULTS: A median of 4 maintenance cycles was administered (range, pemetrexed 1-44; mean ± SD 7.9 ± 8.3; placebo 1-38; mean ± SD 5.0 ± 5.2), with 28% of pemetrexed and 12% of placebo patients receiving ≥ 10 maintenance cycles. The pemetrexed dose intensity was 94%. More patients receiving pemetrexed (12%) than placebo discontinued because of possible drug-related CTCAEs (4%; P = .005). Overall, pemetrexed was associated with significantly more (P < .05) low-grade events (grade 1/2 nausea, grade 2 anemia, edema, and neutropenia) than placebo. Overall, the incidence of low-grade fatigue, anemia, and neutropenia decreased with long-term pemetrexed exposure; however, renal events increased across treatment arms. EQ-5D analyses demonstrated no treatment-by-time interaction or overall treatment differences between the 2 arms. CONCLUSION: PARAMOUNT demonstrated a low incidence of low-grade toxicities with long-term pemetrexed exposure without compromising QoL in patients with NS-NSCLC.
RCT Entities:
INTRODUCTION: In the PARAMOUNT ("A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance Pemetrexed plus Best Supportive Care vs. Best Supportive Care Immediately Following Induction Treatment with Pemetrexed Plus Cisplatin for Advanced Non-Squamous Non-Small-Cell Lung Cancer") trial, patients with advanced nonsquamous non-small-cell lung cancer (NS-NSCLC) benefited from pemetrexed maintenance therapy after induction therapy with pemetrexed and cisplatin by extending survival, delaying disease progression, and maintaining quality of life (QoL). However, low-grade 1 or 2 toxicities during long-term maintenance treatment may become burdensome and impact QoL. MATERIALS AND METHODS:Patients in this double-blind study (n = 539), who had completed 4 induction cycles (pemetrexed with cisplatin) without progressive disease (PD) and had an ECOG performance status of 0/1, were randomized 2:1 to pemetrexed maintenance (500 mg/m(2), day 1) plus best supportive care (BSC) or placebo plus BSC until PD. Adverse events (by maximum Common Terminology Criteria for Adverse Events [CTCAE] grade) and QoL (EuroQol 5-dimensional [EQ-5D] scale) were assessed. RESULTS: A median of 4 maintenance cycles was administered (range, pemetrexed 1-44; mean ± SD 7.9 ± 8.3; placebo 1-38; mean ± SD 5.0 ± 5.2), with 28% of pemetrexed and 12% of placebo patients receiving ≥ 10 maintenance cycles. The pemetrexed dose intensity was 94%. More patients receiving pemetrexed (12%) than placebo discontinued because of possible drug-related CTCAEs (4%; P = .005). Overall, pemetrexed was associated with significantly more (P < .05) low-grade events (grade 1/2 nausea, grade 2 anemia, edema, and neutropenia) than placebo. Overall, the incidence of low-grade fatigue, anemia, and neutropenia decreased with long-term pemetrexed exposure; however, renal events increased across treatment arms. EQ-5D analyses demonstrated no treatment-by-time interaction or overall treatment differences between the 2 arms. CONCLUSION: PARAMOUNT demonstrated a low incidence of low-grade toxicities with long-term pemetrexed exposure without compromising QoL in patients with NS-NSCLC.
Authors: Monika Sztankay; Johannes Maria Giesinger; August Zabernigg; Elisabeth Krempler; Georg Pall; Wolfgang Hilbe; Otto Burghuber; Maximilian Hochmair; Gerhard Rumpold; Stephan Doering; Bernhard Holzner Journal: BMC Cancer Date: 2017-08-23 Impact factor: 4.430
Authors: Nikki de Rouw; Merel de Boer; René J Boosman; Michel M van den Heuvel; David M Burger; Joris E Lieverse; Hieronymus J Derijks; Geert W J Frederix; Rob Ter Heine Journal: Clin Pharmacol Ther Date: 2022-02-21 Impact factor: 6.903