Brain metastases as the primary site of relapse in two randomized phase III pemetrexed trials in advanced nonsmall-cell lung cancer

Waldo Ortuzar, Nasser Hanna, Eduardo Pennella, Guangbin Peng, Corey Langer, Matthew Monberg, Giorgio Scagliotti

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Symptomatic brain metastases (BM) frequently occurs after initial treatment of nonsmall-cell lung cancer (NSCLC). Therefore, 2 large randomized trials that involved pemetrexed were retrospectively analyzed to determine the pattern of symptomatic relapse in the brain and to gauge if pemetrexed could influence the incidence. Two large phase III studies of pemetrexed in advanced NSCLC were included. One study compared pemetrexed with docetaxel in previously treated patients (n = 571); the other study tested cisplatin plus pemetrexed vs. cisplatin plus gemcitabine in chemotherapy-naive patients with advanced NSCLC (n = 1725). Patients with known BM at study entry were excluded from this analysis. Each study was analyzed separately, then jointly to determine the rate of BM reported as the only site of progressive disease by treatment group and histology. Logistic regression was used to obtain an odds ratio for the treatment effect on the overall occurrence of BM while controlling for potential confounding factors. Overall, 71.5% of patients in pemetrexed-containing arms (819 of 1145), and 68.2% of patients in nonpemetrexed-containing arms (785 of 1151) experienced progressive disease. BM recurrence rates were 3.2% (95% confidence interval [CI], 2.1%-4.6%) in the pemetrexed-containing arms vs. 6.6% (95% CI, 5.0%-8.6%) in the nonpemetrexed-containing arms (P =.002). The odds ratio for BM recurrence associated with exposure to pemetrexed was 0.49 (95% CI, 0.32-0.76; P =.001). The beneficial effect of pemetrexed on BM was confined to patients with nonsquamous NSCLC. Patients with advanced nonsquamous NSCLC treated with pemetrexed either in first-line or second-line therapy may reduce the risk of developing BM as the first site of progressive disease. This retrospective analysis is limited due to the lack of baseline and periodic brain scans, and it reflects symptomatic BM only. Regardless, these findings suggest a potential beneficial effect of pemetrexed-based treatments on the control of BM.

Original languageEnglish
Pages (from-to)24-30
Number of pages7
JournalClinical Lung Cancer
Volume13
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

Pemetrexed
Non-Small Cell Lung Carcinoma
Neoplasm Metastasis
Recurrence
Brain
docetaxel
Confidence Intervals
gemcitabine
Cisplatin
Odds Ratio
Therapeutics

Keywords

  • Brain metastases
  • Nonsmall-cell lung cancer
  • Pemetrexed
  • Symptomatic

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Brain metastases as the primary site of relapse in two randomized phase III pemetrexed trials in advanced nonsmall-cell lung cancer. / Ortuzar, Waldo; Hanna, Nasser; Pennella, Eduardo; Peng, Guangbin; Langer, Corey; Monberg, Matthew; Scagliotti, Giorgio.

In: Clinical Lung Cancer, Vol. 13, No. 1, 01.2012, p. 24-30.

Research output: Contribution to journalArticle

Ortuzar, Waldo ; Hanna, Nasser ; Pennella, Eduardo ; Peng, Guangbin ; Langer, Corey ; Monberg, Matthew ; Scagliotti, Giorgio. / Brain metastases as the primary site of relapse in two randomized phase III pemetrexed trials in advanced nonsmall-cell lung cancer. In: Clinical Lung Cancer. 2012 ; Vol. 13, No. 1. pp. 24-30.
@article{0cff61debeb64ccd9d21cc8a0d9a0888,
title = "Brain metastases as the primary site of relapse in two randomized phase III pemetrexed trials in advanced nonsmall-cell lung cancer",
abstract = "Symptomatic brain metastases (BM) frequently occurs after initial treatment of nonsmall-cell lung cancer (NSCLC). Therefore, 2 large randomized trials that involved pemetrexed were retrospectively analyzed to determine the pattern of symptomatic relapse in the brain and to gauge if pemetrexed could influence the incidence. Two large phase III studies of pemetrexed in advanced NSCLC were included. One study compared pemetrexed with docetaxel in previously treated patients (n = 571); the other study tested cisplatin plus pemetrexed vs. cisplatin plus gemcitabine in chemotherapy-naive patients with advanced NSCLC (n = 1725). Patients with known BM at study entry were excluded from this analysis. Each study was analyzed separately, then jointly to determine the rate of BM reported as the only site of progressive disease by treatment group and histology. Logistic regression was used to obtain an odds ratio for the treatment effect on the overall occurrence of BM while controlling for potential confounding factors. Overall, 71.5{\%} of patients in pemetrexed-containing arms (819 of 1145), and 68.2{\%} of patients in nonpemetrexed-containing arms (785 of 1151) experienced progressive disease. BM recurrence rates were 3.2{\%} (95{\%} confidence interval [CI], 2.1{\%}-4.6{\%}) in the pemetrexed-containing arms vs. 6.6{\%} (95{\%} CI, 5.0{\%}-8.6{\%}) in the nonpemetrexed-containing arms (P =.002). The odds ratio for BM recurrence associated with exposure to pemetrexed was 0.49 (95{\%} CI, 0.32-0.76; P =.001). The beneficial effect of pemetrexed on BM was confined to patients with nonsquamous NSCLC. Patients with advanced nonsquamous NSCLC treated with pemetrexed either in first-line or second-line therapy may reduce the risk of developing BM as the first site of progressive disease. This retrospective analysis is limited due to the lack of baseline and periodic brain scans, and it reflects symptomatic BM only. Regardless, these findings suggest a potential beneficial effect of pemetrexed-based treatments on the control of BM.",
keywords = "Brain metastases, Nonsmall-cell lung cancer, Pemetrexed, Symptomatic",
author = "Waldo Ortuzar and Nasser Hanna and Eduardo Pennella and Guangbin Peng and Corey Langer and Matthew Monberg and Giorgio Scagliotti",
year = "2012",
month = "1",
doi = "10.1016/j.cllc.2011.05.007",
language = "English",
volume = "13",
pages = "24--30",
journal = "Clinical Lung Cancer",
issn = "1525-7304",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Brain metastases as the primary site of relapse in two randomized phase III pemetrexed trials in advanced nonsmall-cell lung cancer

AU - Ortuzar, Waldo

AU - Hanna, Nasser

AU - Pennella, Eduardo

AU - Peng, Guangbin

AU - Langer, Corey

AU - Monberg, Matthew

AU - Scagliotti, Giorgio

PY - 2012/1

Y1 - 2012/1

N2 - Symptomatic brain metastases (BM) frequently occurs after initial treatment of nonsmall-cell lung cancer (NSCLC). Therefore, 2 large randomized trials that involved pemetrexed were retrospectively analyzed to determine the pattern of symptomatic relapse in the brain and to gauge if pemetrexed could influence the incidence. Two large phase III studies of pemetrexed in advanced NSCLC were included. One study compared pemetrexed with docetaxel in previously treated patients (n = 571); the other study tested cisplatin plus pemetrexed vs. cisplatin plus gemcitabine in chemotherapy-naive patients with advanced NSCLC (n = 1725). Patients with known BM at study entry were excluded from this analysis. Each study was analyzed separately, then jointly to determine the rate of BM reported as the only site of progressive disease by treatment group and histology. Logistic regression was used to obtain an odds ratio for the treatment effect on the overall occurrence of BM while controlling for potential confounding factors. Overall, 71.5% of patients in pemetrexed-containing arms (819 of 1145), and 68.2% of patients in nonpemetrexed-containing arms (785 of 1151) experienced progressive disease. BM recurrence rates were 3.2% (95% confidence interval [CI], 2.1%-4.6%) in the pemetrexed-containing arms vs. 6.6% (95% CI, 5.0%-8.6%) in the nonpemetrexed-containing arms (P =.002). The odds ratio for BM recurrence associated with exposure to pemetrexed was 0.49 (95% CI, 0.32-0.76; P =.001). The beneficial effect of pemetrexed on BM was confined to patients with nonsquamous NSCLC. Patients with advanced nonsquamous NSCLC treated with pemetrexed either in first-line or second-line therapy may reduce the risk of developing BM as the first site of progressive disease. This retrospective analysis is limited due to the lack of baseline and periodic brain scans, and it reflects symptomatic BM only. Regardless, these findings suggest a potential beneficial effect of pemetrexed-based treatments on the control of BM.

AB - Symptomatic brain metastases (BM) frequently occurs after initial treatment of nonsmall-cell lung cancer (NSCLC). Therefore, 2 large randomized trials that involved pemetrexed were retrospectively analyzed to determine the pattern of symptomatic relapse in the brain and to gauge if pemetrexed could influence the incidence. Two large phase III studies of pemetrexed in advanced NSCLC were included. One study compared pemetrexed with docetaxel in previously treated patients (n = 571); the other study tested cisplatin plus pemetrexed vs. cisplatin plus gemcitabine in chemotherapy-naive patients with advanced NSCLC (n = 1725). Patients with known BM at study entry were excluded from this analysis. Each study was analyzed separately, then jointly to determine the rate of BM reported as the only site of progressive disease by treatment group and histology. Logistic regression was used to obtain an odds ratio for the treatment effect on the overall occurrence of BM while controlling for potential confounding factors. Overall, 71.5% of patients in pemetrexed-containing arms (819 of 1145), and 68.2% of patients in nonpemetrexed-containing arms (785 of 1151) experienced progressive disease. BM recurrence rates were 3.2% (95% confidence interval [CI], 2.1%-4.6%) in the pemetrexed-containing arms vs. 6.6% (95% CI, 5.0%-8.6%) in the nonpemetrexed-containing arms (P =.002). The odds ratio for BM recurrence associated with exposure to pemetrexed was 0.49 (95% CI, 0.32-0.76; P =.001). The beneficial effect of pemetrexed on BM was confined to patients with nonsquamous NSCLC. Patients with advanced nonsquamous NSCLC treated with pemetrexed either in first-line or second-line therapy may reduce the risk of developing BM as the first site of progressive disease. This retrospective analysis is limited due to the lack of baseline and periodic brain scans, and it reflects symptomatic BM only. Regardless, these findings suggest a potential beneficial effect of pemetrexed-based treatments on the control of BM.

KW - Brain metastases

KW - Nonsmall-cell lung cancer

KW - Pemetrexed

KW - Symptomatic

UR - http://www.scopus.com/inward/record.url?scp=84855709286&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855709286&partnerID=8YFLogxK

U2 - 10.1016/j.cllc.2011.05.007

DO - 10.1016/j.cllc.2011.05.007

M3 - Article

C2 - 21831719

AN - SCOPUS:84855709286

VL - 13

SP - 24

EP - 30

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

SN - 1525-7304

IS - 1

ER -