Treatment-by-histology interaction analyses in three phase III trials show superiority of pemetrexed in nonsquamous non-small cell lung cancer

Giorgio Scagliotti, Thomas Brodowicz, Frances A. Shepherd, Christoph Zielinski, Johan Vansteenkiste, Christian Manegold, Lorinda Simms, Frank Fossella, Katherine Sugarman, Chandra Belani

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Abstract

INTRODUCTION: Recently, histology has emerged as a predictive factor for pemetrexed efficacy in non-small cell lung cancer (NSCLC). These analyses evaluate whether the differential efficacy of pemetrexed by NSCLC histology is reproducible and consistent across three registration studies of different lines of therapy (first-line/second-line and maintenance settings). METHODS: The reported studies for patients with advanced NSCLC were pemetrexed versus docetaxel in previously treated patients (N = 571), cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (N = 1725), and maintenance pemetrexed plus best supportive care versus placebo plus best supportive care (N = 663). Cox models of overall survival (OS) and progression-free survival (PFS) were used to test for a significant treatment-by-histology interaction (THI). A significant THI indicates that the efficacy benefit for pemetrexed relative to the control arm is greater in patients with nonsquamous histology than in those with squamous histology. Subsequent Cox models were used to estimate hazard ratios for OS and PFS according to histology. RESULTS: Histology was well balanced between treatment arms in each study. Across all three studies, no clinically relevant differences were observed for the safety profile of pemetrexed among histologic groups. THIs were statistically significant in all three studies for OS (p = 0.001, 0.002, and 0.033, respectively) and PFS (p = 0.004, 0.002, and 0.036, respectively). CONCLUSIONS: These analyses demonstrate a statistically significant interaction between treatment effect and NSCLC histology, indicating superior efficacy of pemetrexed in nonsquamous patients compared with other standard treatment options. Thus, histology is consistently predictive of the improved efficacy of pemetrexed in patients with nonsquamous NSCLC.

Original languageEnglish (US)
Pages (from-to)64-70
Number of pages7
JournalJournal of Thoracic Oncology
Volume6
Issue number1
DOIs
StatePublished - Jan 1 2011

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Pemetrexed
Non-Small Cell Lung Carcinoma
Histology
Disease-Free Survival
Therapeutics
docetaxel
gemcitabine
Proportional Hazards Models
Cisplatin
Survival
Maintenance

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Scagliotti, Giorgio ; Brodowicz, Thomas ; Shepherd, Frances A. ; Zielinski, Christoph ; Vansteenkiste, Johan ; Manegold, Christian ; Simms, Lorinda ; Fossella, Frank ; Sugarman, Katherine ; Belani, Chandra. / Treatment-by-histology interaction analyses in three phase III trials show superiority of pemetrexed in nonsquamous non-small cell lung cancer. In: Journal of Thoracic Oncology. 2011 ; Vol. 6, No. 1. pp. 64-70.
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title = "Treatment-by-histology interaction analyses in three phase III trials show superiority of pemetrexed in nonsquamous non-small cell lung cancer",
abstract = "INTRODUCTION: Recently, histology has emerged as a predictive factor for pemetrexed efficacy in non-small cell lung cancer (NSCLC). These analyses evaluate whether the differential efficacy of pemetrexed by NSCLC histology is reproducible and consistent across three registration studies of different lines of therapy (first-line/second-line and maintenance settings). METHODS: The reported studies for patients with advanced NSCLC were pemetrexed versus docetaxel in previously treated patients (N = 571), cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (N = 1725), and maintenance pemetrexed plus best supportive care versus placebo plus best supportive care (N = 663). Cox models of overall survival (OS) and progression-free survival (PFS) were used to test for a significant treatment-by-histology interaction (THI). A significant THI indicates that the efficacy benefit for pemetrexed relative to the control arm is greater in patients with nonsquamous histology than in those with squamous histology. Subsequent Cox models were used to estimate hazard ratios for OS and PFS according to histology. RESULTS: Histology was well balanced between treatment arms in each study. Across all three studies, no clinically relevant differences were observed for the safety profile of pemetrexed among histologic groups. THIs were statistically significant in all three studies for OS (p = 0.001, 0.002, and 0.033, respectively) and PFS (p = 0.004, 0.002, and 0.036, respectively). CONCLUSIONS: These analyses demonstrate a statistically significant interaction between treatment effect and NSCLC histology, indicating superior efficacy of pemetrexed in nonsquamous patients compared with other standard treatment options. Thus, histology is consistently predictive of the improved efficacy of pemetrexed in patients with nonsquamous NSCLC.",
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Scagliotti, G, Brodowicz, T, Shepherd, FA, Zielinski, C, Vansteenkiste, J, Manegold, C, Simms, L, Fossella, F, Sugarman, K & Belani, C 2011, 'Treatment-by-histology interaction analyses in three phase III trials show superiority of pemetrexed in nonsquamous non-small cell lung cancer', Journal of Thoracic Oncology, vol. 6, no. 1, pp. 64-70. https://doi.org/10.1097/JTO.0b013e3181f7c6d4

Treatment-by-histology interaction analyses in three phase III trials show superiority of pemetrexed in nonsquamous non-small cell lung cancer. / Scagliotti, Giorgio; Brodowicz, Thomas; Shepherd, Frances A.; Zielinski, Christoph; Vansteenkiste, Johan; Manegold, Christian; Simms, Lorinda; Fossella, Frank; Sugarman, Katherine; Belani, Chandra.

In: Journal of Thoracic Oncology, Vol. 6, No. 1, 01.01.2011, p. 64-70.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Treatment-by-histology interaction analyses in three phase III trials show superiority of pemetrexed in nonsquamous non-small cell lung cancer

AU - Scagliotti, Giorgio

AU - Brodowicz, Thomas

AU - Shepherd, Frances A.

AU - Zielinski, Christoph

AU - Vansteenkiste, Johan

AU - Manegold, Christian

AU - Simms, Lorinda

AU - Fossella, Frank

AU - Sugarman, Katherine

AU - Belani, Chandra

PY - 2011/1/1

Y1 - 2011/1/1

N2 - INTRODUCTION: Recently, histology has emerged as a predictive factor for pemetrexed efficacy in non-small cell lung cancer (NSCLC). These analyses evaluate whether the differential efficacy of pemetrexed by NSCLC histology is reproducible and consistent across three registration studies of different lines of therapy (first-line/second-line and maintenance settings). METHODS: The reported studies for patients with advanced NSCLC were pemetrexed versus docetaxel in previously treated patients (N = 571), cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (N = 1725), and maintenance pemetrexed plus best supportive care versus placebo plus best supportive care (N = 663). Cox models of overall survival (OS) and progression-free survival (PFS) were used to test for a significant treatment-by-histology interaction (THI). A significant THI indicates that the efficacy benefit for pemetrexed relative to the control arm is greater in patients with nonsquamous histology than in those with squamous histology. Subsequent Cox models were used to estimate hazard ratios for OS and PFS according to histology. RESULTS: Histology was well balanced between treatment arms in each study. Across all three studies, no clinically relevant differences were observed for the safety profile of pemetrexed among histologic groups. THIs were statistically significant in all three studies for OS (p = 0.001, 0.002, and 0.033, respectively) and PFS (p = 0.004, 0.002, and 0.036, respectively). CONCLUSIONS: These analyses demonstrate a statistically significant interaction between treatment effect and NSCLC histology, indicating superior efficacy of pemetrexed in nonsquamous patients compared with other standard treatment options. Thus, histology is consistently predictive of the improved efficacy of pemetrexed in patients with nonsquamous NSCLC.

AB - INTRODUCTION: Recently, histology has emerged as a predictive factor for pemetrexed efficacy in non-small cell lung cancer (NSCLC). These analyses evaluate whether the differential efficacy of pemetrexed by NSCLC histology is reproducible and consistent across three registration studies of different lines of therapy (first-line/second-line and maintenance settings). METHODS: The reported studies for patients with advanced NSCLC were pemetrexed versus docetaxel in previously treated patients (N = 571), cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (N = 1725), and maintenance pemetrexed plus best supportive care versus placebo plus best supportive care (N = 663). Cox models of overall survival (OS) and progression-free survival (PFS) were used to test for a significant treatment-by-histology interaction (THI). A significant THI indicates that the efficacy benefit for pemetrexed relative to the control arm is greater in patients with nonsquamous histology than in those with squamous histology. Subsequent Cox models were used to estimate hazard ratios for OS and PFS according to histology. RESULTS: Histology was well balanced between treatment arms in each study. Across all three studies, no clinically relevant differences were observed for the safety profile of pemetrexed among histologic groups. THIs were statistically significant in all three studies for OS (p = 0.001, 0.002, and 0.033, respectively) and PFS (p = 0.004, 0.002, and 0.036, respectively). CONCLUSIONS: These analyses demonstrate a statistically significant interaction between treatment effect and NSCLC histology, indicating superior efficacy of pemetrexed in nonsquamous patients compared with other standard treatment options. Thus, histology is consistently predictive of the improved efficacy of pemetrexed in patients with nonsquamous NSCLC.

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