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

H. Chen, M. R. Modiano, J. W. Neal, J. R. Brahmer, J. R. Rigas, R. M. Jotte, N. B. Leighl, Jonathan Riess, C. J. Kuo, L. Liu, B. Gao, A. T. Dicioccio, A. A. Adjei, H. A. Wakelee

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)602-608
Number of pages7
JournalBritish Journal of Cancer
Volume110
Issue number3
DOIs
StatePublished - Feb 4 2014
Externally publishedYes

Fingerprint

Pemetrexed
Non-Small Cell Lung Carcinoma
Cisplatin
Multicenter Studies
Posterior Leukoencephalopathy Syndrome
Disease-Free Survival
Hypertension
Sample Size
Nausea
Fatigue
Disease Progression
aflibercept
Maintenance
Kidney
Safety

Keywords

  • anti-angiogenesis
  • non-small cell lung cancer
  • reversible posterior leukoencephalopathy syndrome
  • ziv-aflibercept

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Chen, H.; Modiano, M. R.; Neal, J. W.; Brahmer, J. R.; Rigas, J. R.; Jotte, R. M.; Leighl, N. B.; Riess, Jonathan; Kuo, C. J.; Liu, L.; Gao, B.; Dicioccio, A. T.; Adjei, A. A.; Wakelee, H. A.

In: British Journal of Cancer, Vol. 110, No. 3, 04.02.2014, p. 602-608.

Research output: Contribution to journalArticle

Chen, H, Modiano, MR, Neal, JW, Brahmer, JR, Rigas, JR, Jotte, RM, Leighl, NB, Riess, J, Kuo, CJ, Liu, L, Gao, B, Dicioccio, AT, Adjei, AA & Wakelee, HA 2014, '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', British Journal of Cancer, vol. 110, no. 3, pp. 602-608. https://doi.org/10.1038/bjc.2013.735
Chen, H. ; Modiano, M. R. ; Neal, J. W. ; Brahmer, J. R. ; Rigas, J. R. ; Jotte, R. M. ; Leighl, N. B. ; Riess, Jonathan ; Kuo, C. J. ; Liu, L. ; Gao, B. ; Dicioccio, A. T. ; Adjei, A. A. ; Wakelee, H. A. / 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. In: British Journal of Cancer. 2014 ; Vol. 110, No. 3. pp. 602-608.
@article{75a66e95299d4ec9be4e017b60d6cb90,
title = "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.",
keywords = "anti-angiogenesis, non-small cell lung cancer, reversible posterior leukoencephalopathy syndrome, ziv-aflibercept",
author = "H. Chen and Modiano, {M. R.} and Neal, {J. W.} and Brahmer, {J. R.} and Rigas, {J. R.} and Jotte, {R. M.} and Leighl, {N. B.} and Jonathan Riess and Kuo, {C. J.} and L. Liu and B. Gao and Dicioccio, {A. T.} and Adjei, {A. A.} and Wakelee, {H. A.}",
year = "2014",
month = "2",
day = "4",
doi = "10.1038/bjc.2013.735",
language = "English (US)",
volume = "110",
pages = "602--608",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - 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

AU - Chen, H.

AU - Modiano, M. R.

AU - Neal, J. W.

AU - Brahmer, J. R.

AU - Rigas, J. R.

AU - Jotte, R. M.

AU - Leighl, N. B.

AU - Riess, Jonathan

AU - Kuo, C. J.

AU - Liu, L.

AU - Gao, B.

AU - Dicioccio, A. T.

AU - Adjei, A. A.

AU - Wakelee, H. A.

PY - 2014/2/4

Y1 - 2014/2/4

N2 - 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.

AB - 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.

KW - anti-angiogenesis

KW - non-small cell lung cancer

KW - reversible posterior leukoencephalopathy syndrome

KW - ziv-aflibercept

UR - http://www.scopus.com/inward/record.url?scp=84893745037&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893745037&partnerID=8YFLogxK

U2 - 10.1038/bjc.2013.735

DO - 10.1038/bjc.2013.735

M3 - Article

C2 - 24292447

AN - SCOPUS:84893745037

VL - 110

SP - 602

EP - 608

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 3

ER -