A phase II multicentre study of ziv-aflibercept in combination with cisplatin and pemetrexed in patients with previously untreated advanced/metastatic non-squamous non-small cell lung cancer.

Abstract

BACKGROUND:

This study evaluated the efficacy and safety of ziv-aflibercept in combination with cisplatin and pemetrexed in non-small cell lung cancer (NSCLC).

METHODS:

This single arm, multicentre phase II trial enrolled patients with previously untreated, locally advanced or metastatic non-squamous NSCLC. Patients received intravenous ziv-aflibercept 6 mg kg(-1), pemetrexed 500 mg m(-2), and cisplatin 75 mg m(-2), every 21 days for up to six cycles. Maintenance administration of ziv-aflibercept was to continue until disease progression, intolerable toxicity or other cause for withdrawal. The co-primary end points were objective response rate (ORR) and progression-free survival (PFS). Planned sample size was 72 patients.

RESULTS:

The study was closed prematurely because of three confirmed and two suspected cases of reversible posterior leukoencephalopathy syndrome (RPLS). A total of 42 patients were enrolled. Median age was 61.5 years; 55% were male, 86% Caucasian and 50% had Eastern Cooperative Oncology Group performance status (ECOG PS)=0. A median of four cycles of ziv-aflibercept was administered. The most common treatment-emergent adverse events (TEAEs) of any grade were nausea (69%) and fatigue (67%), with hypertension (36%) as the most common grade 3/4 TEAE. Of the 38 evaluable patients, ORR was 26% and median PFS was 5 months.

CONCLUSION:

Cases of RPLS had been observed in other studies in the ziv-aflibercept clinical development programme but the rate observed in this study was higher than previously observed. This might be related to declining renal function and/or hypertension. Although ORR and PFS were in accordance with most historical first-line NSCLC studies, this combination of ziv-aflibercept/cisplatin/pemetrexed will not be further explored in NSCLC.

• Authors: H Chen, M R Modiano, J W Neal, J R Brahmer, J R Rigas, R M Jotte, N B Leighl, J W Riess, C J Kuo, L Liu, B Gao, A T Dicioccio, A A Adjei, H A Wakelee
• Journal: British journal of cancer (Br J Cancer) Vol. 110 Issue 3 Pg. 602-8 (Feb 04 2014) ISSN: 1532-1827 [Electronic] England
• PMID: 24292447 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamates
• Recombinant Fusion Proteins
• Pemetrexed
• aflibercept
• Guanine
• Receptors, Vascular Endothelial Growth Factor
• Cisplatin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality, pathology)
• Cisplatin (administration & dosage, adverse effects)
• Disease-Free Survival
• Drug-Related Side Effects and Adverse Reactions (classification, pathology)
• Female
• Glutamates (administration & dosage, adverse effects)
• Guanine (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Pemetrexed
• Receptors, Vascular Endothelial Growth Factor (administration & dosage, adverse effects)
• Recombinant Fusion Proteins (administration & dosage, adverse effects)
• Treatment Outcome