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Clin Lung Cancer. 2017 Sep;18(5):489-496. doi: 10.1016/j.cllc.2017.04.003. Epub 2017 Apr 12.

Safety Analyses of Pemetrexed-cisplatin and Pemetrexed Maintenance Therapies in Patients With Advanced Non-squamous NSCLC: Retrospective Analyses From 2 Phase III Studies.

Author information

1
University of Pennsylvania, Perelman Center for Advanced Medicine, Philadelphia, PA.
2
Instituto de Biomedicina de Sevilla (University Hospital Virgen del Rocío, CSIC and Seville University), Seville, Spain.
3
Wayne State University School of Medicine, Detroit, MI; Karmanos Cancer Institute, Detroit, MI.
4
Division of Medical Oncology, S. G. Moscati Hospital, Avellino, Italy.
5
San Camillo, High Specialization Hospital, Rome, Italy; Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy.
6
Montpellier University Hospital, Montpellier, France.
7
Eli Lilly and Company, Madrid, Spain.
8
Eli Lilly and Company, Indianapolis, IN.
9
Eli Lilly and Company, Houten, The Netherlands.
10
University of Turin, Thoracic Oncology Unit, Turin, Italy. Electronic address: scagliotti@ihnet.it.

Abstract

BACKGROUND:

In a phase III study, maintenance pemetrexed showed superior survival over placebo (PARAMOUNT) for patients with advanced non-squamous non-small cell lung cancer (NSCLC) who completed 4 cycles of pemetrexed plus cisplatin (PC) induction therapy, with low incidence of treatment-emergent adverse events (TEAEs) generally associated with pemetrexed. Prior analyses did not account for toxicities carried over from induction; thus, the current analysis was developed to understand toxicities that may be attributed to pemetrexed maintenance versus PC induction, and how treatment duration affects toxicity.

PATIENTS AND METHODS:

Selected clinically relevant TEAEs were explored in 2 analyses: assessing induction versus maintenance treatment in PARAMOUNT, and comparing PC from PARAMOUNT with toxicity data from a previous phase III study that established the role of PC in front-line therapy of non-squamous NSCLC (JMDB trial).

RESULTS:

In PARAMOUNT, the incidence of most drug-related TEAEs was higher during induction than maintenance, for both the pemetrexed and placebo randomized populations. The majority of TEAEs during maintenance, except renal events, were carried over from induction with no change in severity from the end of induction; the incidence of TEAEs associated with pemetrexed maintenance was low. The cross-trial analysis showed that 6 cycles of PC in JMDB compared with 4 cycles in PARAMOUNT increased grade 1/2 fatigue (34.1% vs. 25.0%), anemia (24.0% vs. 13.5%), and renal events (11.8% vs. 3.6%).

CONCLUSIONS:

Safety data presented here support the favorable risk benefit of 4 cycles of PC followed by maintenance pemetrexed in patients with advanced non-squamous NSCLC.

KEYWORDS:

Adverse events; Cross-trial analysis; First-line treatment; Post-hoc analysis; Treatment duration

PMID:
28479368
DOI:
10.1016/j.cllc.2017.04.003
[Indexed for MEDLINE]

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