A randomised phase II study of pemetrexed versus pemetrexed + erlotinib as second-line treatment for locally advanced or metastatic non-squamous non-small cell lung cancer
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INTRODUCTION
Of the NSCLC patients experiencing disease progression after first-line standard therapy, about 40–50% will receive second-line therapy [1]. However, only limited therapeutic options are available for second-line treatment [2]. The choice of any second-line treatment should represent a rational selection of a drug or drug combination depending on their activity against tumours pretreated with distinct first-line therapies [3].
Currently, three cytotoxic or cytostatic agents are approved for
Study design
This multicentre, randomised, phase II, open-label, parallel trial was designed to evaluate PFS of pemetrexed and pemetrexed plus erlotinib in an overall advanced NSCLC patient population. The study enrolled its first patient in April 2007. Following a label change for Alimta (pemetrexed) in EU and the USA [13], [5] restricting the patient population to non-squamous NSCLC only, the protocol was amended (approved on 1st August 2008) to narrow the patient population to non-squamous NSCLC to bring
Patient disposition
This study was conducted at 24 study centres in five countries (Austria, Germany, Hungary, Spain, and Sweden) from 11th April 2007 to 27th July 2010 (primary analysis cut-off date). One hundred and sixty-five patients with non-squamous NSCLC of the total enrolled patient population (N = 214) were randomly assigned to a treatment arm (Fig. 1); 159 of these patients received at least one dose of study treatment (pemetrexed, n = 83; pemetrexed + erotinib, n = 76). Three patients treated with pemetrexed +
Discussion
The combination of pemetrexed with erlotinib as second-line treatment in patients with advanced or metastatic non-squamous NSCLC yielded a statistically significant improvement in PFS (HR 0.63; 95% CI: 0.44, 0.90; log-rank P = 0.0047) compared with single-agent pemetrexed. Thus, the primary study objective was met. Although it might be argued that the envisaged difference of one third increase in PFS is somewhat low – especially with regard to actual expectations from novel targeted drugs tested
Role of the funding source
This study was sponsored by Eli Lilly and Company, Indianapolis, IN, USA. Eli Lilly provided the study medication and collaborated with the principal investigator/investigators on study concept, study design, quality control, data analysis and interpretation, statistical analysis and preparation of this report. The investigators had final responsibility for the content of the report and for the decision to submit for publication.
Conflict of interest statement
Professor Dittrich received honoraria from Eli Lilly and Genentech/Roche. The research institutes headed by Professor Dittrich received research grants from Eli Lilly and Roche Austria. Dr. von Pawel is a member of advisory boards of Daiichi Sankyo, Eli Lilly and Pfizer and also received speaker fees. Dr. Hartmann received research support from Eli Lilly. Dr. Behringer is a member of advisory boards of Roche and Eli Lilly. Drs. Papai-Szekely and Vinolas have no relevant financial disclosure.
Acknowledgements
The authors wish to thank all the investigators and patients who participated in this study.
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A Review of Regimens Combining Pemetrexed With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in the Treatment of Advanced Nonsquamous Non–Small-Cell Lung Cancer
2018, Clinical Lung CancerCitation Excerpt :The concurrent regimen is currently being evaluated against gefitinib alone in a randomized phase 3 study (NEJ009).51 The efficacy and safety of second-line treatment with pemetrexed and concurrent erlotinib was assessed in patients who had failed one prior platinum-based chemotherapy regimen (Study S102).52 In this open-label, randomized, phase 2 study, patients with advanced nonsquamous NSCLC, and unselected with respect to EGFR mutations, were randomized to second-line treatment with pemetrexed alone (500 mg/m2 every 3 weeks; n = 83) or concurrent pemetrexed (500 mg/m2 every 3 weeks) plus erlotinib (150 mg/d; n = 76).
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2017, ESMO OpenCitation Excerpt :Therefore, patients with treatment-naïve lung adenocarcinoma with EGFR mutation may have the most benefit from E-P treatment. Pemetrexed–erlotinib significantly improved PFS or OS compared with erlotinib or pemetrexed alone in non-squamous NSCLC, and superior results were observed often in non-smokers or East Asians harbouring EGFR mutation.6–8 21 Unfortunately, these were all phase II trials.
Pemetrexed with Platinum Combination as a Backbone for Targeted Therapy in Non-Small-Cell Lung Cancer
2016, Clinical Lung CancerCitation Excerpt :The most common grade 3/4 hematologic toxicities were anemia, neutropenia, thrombocytopenia, febrile neutropenia, rash, and diarrhea (NCT00447057). No biomarker assessment was done for this trial.16 Last, a recently completed study by Lee et al17 compared the combination of pemetrexed and erlotinib with single-agent pemetrexed or erlotinib as second-line therapy in patients with advanced or metastatic nonsquamous NSCLC.
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2015, Clinical Lung CancerCitation Excerpt :Multiple studies have evaluated combination therapy with pemetrexed with a novel agent, such as erlotinib, bevacizumab, gefitinib, and sunitinib, but none have demonstrated improvements in overall survival (OS). Combination therapy in general is associated with more adverse events (AEs) than standard chemotherapy alone.4-6 However, because of the favorable safety profile of pemetrexed, it is reasonable to evaluate it in combination with a novel targeted agent that has a favorable safety profile.
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