Randomized prospective biomarker trial of ERCC1 for comparing platinum and nonplatinum therapy in advanced non-small-cell lung cancer: ERCC1 Trial (ET)

Research output: Contribution to journalArticlepeer-review

Standard

Randomized prospective biomarker trial of ERCC1 for comparing platinum and nonplatinum therapy in advanced non-small-cell lung cancer : ERCC1 Trial (ET). / Lee, Siow Ming; Falzon, Mary; Blackhall, Fiona; Spicer, James; Nicolson, Marianne; Chaudhuri, Abhro; Middleton, Gary; Ahmed, Samreen; Hicks, Jonathan; Crosse, Barbara; Napier, Mark; Singer, Julian M; Ferry, David; Lewanski, Conrad; Forster, Martin; Rolls, Sally-Ann; Capitanio, Arrigo; Rudd, Robin; Iles, Natasha; Ngai, Yenting; Gandy, Michael; Lillywhite, Rachel; Hackshaw, Allan.

In: Journal of Clinical Oncology , Vol. 35, No. 4, 01.02.2017, p. 402-411.

Research output: Contribution to journalArticlepeer-review

Harvard

Lee, SM, Falzon, M, Blackhall, F, Spicer, J, Nicolson, M, Chaudhuri, A, Middleton, G, Ahmed, S, Hicks, J, Crosse, B, Napier, M, Singer, JM, Ferry, D, Lewanski, C, Forster, M, Rolls, S-A, Capitanio, A, Rudd, R, Iles, N, Ngai, Y, Gandy, M, Lillywhite, R & Hackshaw, A 2017, 'Randomized prospective biomarker trial of ERCC1 for comparing platinum and nonplatinum therapy in advanced non-small-cell lung cancer: ERCC1 Trial (ET)', Journal of Clinical Oncology , vol. 35, no. 4, pp. 402-411. https://doi.org/10.1200/JCO.2016.68.1841

APA

Lee, S. M., Falzon, M., Blackhall, F., Spicer, J., Nicolson, M., Chaudhuri, A., Middleton, G., Ahmed, S., Hicks, J., Crosse, B., Napier, M., Singer, J. M., Ferry, D., Lewanski, C., Forster, M., Rolls, S-A., Capitanio, A., Rudd, R., Iles, N., ... Hackshaw, A. (2017). Randomized prospective biomarker trial of ERCC1 for comparing platinum and nonplatinum therapy in advanced non-small-cell lung cancer: ERCC1 Trial (ET). Journal of Clinical Oncology , 35(4), 402-411. https://doi.org/10.1200/JCO.2016.68.1841

Vancouver

Author

Lee, Siow Ming ; Falzon, Mary ; Blackhall, Fiona ; Spicer, James ; Nicolson, Marianne ; Chaudhuri, Abhro ; Middleton, Gary ; Ahmed, Samreen ; Hicks, Jonathan ; Crosse, Barbara ; Napier, Mark ; Singer, Julian M ; Ferry, David ; Lewanski, Conrad ; Forster, Martin ; Rolls, Sally-Ann ; Capitanio, Arrigo ; Rudd, Robin ; Iles, Natasha ; Ngai, Yenting ; Gandy, Michael ; Lillywhite, Rachel ; Hackshaw, Allan. / Randomized prospective biomarker trial of ERCC1 for comparing platinum and nonplatinum therapy in advanced non-small-cell lung cancer : ERCC1 Trial (ET). In: Journal of Clinical Oncology . 2017 ; Vol. 35, No. 4. pp. 402-411.

Bibtex

@article{be758b1753034512ad94d1a237c4dd11,
title = "Randomized prospective biomarker trial of ERCC1 for comparing platinum and nonplatinum therapy in advanced non-small-cell lung cancer: ERCC1 Trial (ET)",
abstract = "Purpose Retrospective studies indicate that expression of excision repair cross complementing group 1 (ERCC1) protein is associated with platinum resistance and survival in non-small-cell lung cancer (NSCLC). We conducted the first randomized trial, to our knowledge, to evaluate ERCC1 prospectively and to assess the superiority of nonplatinum therapy over platinum doublet therapy for ERCC1-positive NSCLC as well as noninferiority for ERCC1-negative NSCLC. Patients and Methods This trial had a marker-by-treatment interaction phase III design, with ERCC1 (8F1 antibody) status as a randomization stratification factor. Chemona{\"i}ve patients with NSCLC (stage IIIB and IV) were eligible. Patients with squamous histology were randomly assigned to cisplatin and gemcitabine or paclitaxel and gemcitabine; nonsquamous patients received cisplatin and pemetrexed or paclitaxel and pemetrexed. Primary end point was overall survival (OS). We also evaluated an antibody specific for XPF (clone 3F2). The target hazard ratio (HR) for patients with ERCC1-positive NSCLC was ≤ 0.78. Results Of patients, 648 were recruited (177 squamous, 471 nonsquamous). ERCC1-positive rates were 54.5% and 76.7% in nonsquamous and squamous patients, respectively, and the corresponding XPF-positive rates were 70.5% and 68.5%. Accrual stopped early in 2012 for squamous patients because OS for nonplatinum therapy was inferior to platinum therapy (median OS, 7.6 months [paclitaxel and gemcitabine] v 10.7 months [cisplatin and gemcitabine]; HR, 1.46; P = .02). Accrual for nonsquamous patients halted in 2013. Median OS was 8.0 (paclitaxel and pemetrexed) versus 9.6 (cisplatin and pemetrexed) months for ERCC1-positive patients (HR, 1.11; 95% CI, 0.85 to 1.44), and 10.3 (paclitaxel and pemetrexed) versus 11.6 (cisplatin and pemetrexed) months for ERCC1-negative patients (HR, 0.99; 95% CI, 0.73 to 1.33; interaction P = .64). OS HR was 1.09 (95% CI, 0.83 to 1.44) for XPF-positive patients, and 1.39 (95% CI, 0.90 to 2.15) for XPF-negative patients (interaction P = .35). Neither ERCC1 nor XPF were prognostic: among nonsquamous patients, OS HRs for positive versus negative were ERCC1, 1.11 ( P = .32), and XPF, 1.08 ( P = .55). Conclusion Superior outcomes were observed for patients with squamous histology who received platinum therapy compared with nonplatinum chemotherapy; however, selecting chemotherapy by using commercially available ERCC1 or XPF antibodies did not confer any extra survival benefit.",
author = "Lee, {Siow Ming} and Mary Falzon and Fiona Blackhall and James Spicer and Marianne Nicolson and Abhro Chaudhuri and Gary Middleton and Samreen Ahmed and Jonathan Hicks and Barbara Crosse and Mark Napier and Singer, {Julian M} and David Ferry and Conrad Lewanski and Martin Forster and Sally-Ann Rolls and Arrigo Capitanio and Robin Rudd and Natasha Iles and Yenting Ngai and Michael Gandy and Rachel Lillywhite and Allan Hackshaw",
year = "2017",
month = feb,
day = "1",
doi = "10.1200/JCO.2016.68.1841",
language = "English",
volume = "35",
pages = "402--411",
journal = "Journal of Clinical Oncology ",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "4",

}

RIS

TY - JOUR

T1 - Randomized prospective biomarker trial of ERCC1 for comparing platinum and nonplatinum therapy in advanced non-small-cell lung cancer

T2 - ERCC1 Trial (ET)

AU - Lee, Siow Ming

AU - Falzon, Mary

AU - Blackhall, Fiona

AU - Spicer, James

AU - Nicolson, Marianne

AU - Chaudhuri, Abhro

AU - Middleton, Gary

AU - Ahmed, Samreen

AU - Hicks, Jonathan

AU - Crosse, Barbara

AU - Napier, Mark

AU - Singer, Julian M

AU - Ferry, David

AU - Lewanski, Conrad

AU - Forster, Martin

AU - Rolls, Sally-Ann

AU - Capitanio, Arrigo

AU - Rudd, Robin

AU - Iles, Natasha

AU - Ngai, Yenting

AU - Gandy, Michael

AU - Lillywhite, Rachel

AU - Hackshaw, Allan

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Purpose Retrospective studies indicate that expression of excision repair cross complementing group 1 (ERCC1) protein is associated with platinum resistance and survival in non-small-cell lung cancer (NSCLC). We conducted the first randomized trial, to our knowledge, to evaluate ERCC1 prospectively and to assess the superiority of nonplatinum therapy over platinum doublet therapy for ERCC1-positive NSCLC as well as noninferiority for ERCC1-negative NSCLC. Patients and Methods This trial had a marker-by-treatment interaction phase III design, with ERCC1 (8F1 antibody) status as a randomization stratification factor. Chemonaïve patients with NSCLC (stage IIIB and IV) were eligible. Patients with squamous histology were randomly assigned to cisplatin and gemcitabine or paclitaxel and gemcitabine; nonsquamous patients received cisplatin and pemetrexed or paclitaxel and pemetrexed. Primary end point was overall survival (OS). We also evaluated an antibody specific for XPF (clone 3F2). The target hazard ratio (HR) for patients with ERCC1-positive NSCLC was ≤ 0.78. Results Of patients, 648 were recruited (177 squamous, 471 nonsquamous). ERCC1-positive rates were 54.5% and 76.7% in nonsquamous and squamous patients, respectively, and the corresponding XPF-positive rates were 70.5% and 68.5%. Accrual stopped early in 2012 for squamous patients because OS for nonplatinum therapy was inferior to platinum therapy (median OS, 7.6 months [paclitaxel and gemcitabine] v 10.7 months [cisplatin and gemcitabine]; HR, 1.46; P = .02). Accrual for nonsquamous patients halted in 2013. Median OS was 8.0 (paclitaxel and pemetrexed) versus 9.6 (cisplatin and pemetrexed) months for ERCC1-positive patients (HR, 1.11; 95% CI, 0.85 to 1.44), and 10.3 (paclitaxel and pemetrexed) versus 11.6 (cisplatin and pemetrexed) months for ERCC1-negative patients (HR, 0.99; 95% CI, 0.73 to 1.33; interaction P = .64). OS HR was 1.09 (95% CI, 0.83 to 1.44) for XPF-positive patients, and 1.39 (95% CI, 0.90 to 2.15) for XPF-negative patients (interaction P = .35). Neither ERCC1 nor XPF were prognostic: among nonsquamous patients, OS HRs for positive versus negative were ERCC1, 1.11 ( P = .32), and XPF, 1.08 ( P = .55). Conclusion Superior outcomes were observed for patients with squamous histology who received platinum therapy compared with nonplatinum chemotherapy; however, selecting chemotherapy by using commercially available ERCC1 or XPF antibodies did not confer any extra survival benefit.

AB - Purpose Retrospective studies indicate that expression of excision repair cross complementing group 1 (ERCC1) protein is associated with platinum resistance and survival in non-small-cell lung cancer (NSCLC). We conducted the first randomized trial, to our knowledge, to evaluate ERCC1 prospectively and to assess the superiority of nonplatinum therapy over platinum doublet therapy for ERCC1-positive NSCLC as well as noninferiority for ERCC1-negative NSCLC. Patients and Methods This trial had a marker-by-treatment interaction phase III design, with ERCC1 (8F1 antibody) status as a randomization stratification factor. Chemonaïve patients with NSCLC (stage IIIB and IV) were eligible. Patients with squamous histology were randomly assigned to cisplatin and gemcitabine or paclitaxel and gemcitabine; nonsquamous patients received cisplatin and pemetrexed or paclitaxel and pemetrexed. Primary end point was overall survival (OS). We also evaluated an antibody specific for XPF (clone 3F2). The target hazard ratio (HR) for patients with ERCC1-positive NSCLC was ≤ 0.78. Results Of patients, 648 were recruited (177 squamous, 471 nonsquamous). ERCC1-positive rates were 54.5% and 76.7% in nonsquamous and squamous patients, respectively, and the corresponding XPF-positive rates were 70.5% and 68.5%. Accrual stopped early in 2012 for squamous patients because OS for nonplatinum therapy was inferior to platinum therapy (median OS, 7.6 months [paclitaxel and gemcitabine] v 10.7 months [cisplatin and gemcitabine]; HR, 1.46; P = .02). Accrual for nonsquamous patients halted in 2013. Median OS was 8.0 (paclitaxel and pemetrexed) versus 9.6 (cisplatin and pemetrexed) months for ERCC1-positive patients (HR, 1.11; 95% CI, 0.85 to 1.44), and 10.3 (paclitaxel and pemetrexed) versus 11.6 (cisplatin and pemetrexed) months for ERCC1-negative patients (HR, 0.99; 95% CI, 0.73 to 1.33; interaction P = .64). OS HR was 1.09 (95% CI, 0.83 to 1.44) for XPF-positive patients, and 1.39 (95% CI, 0.90 to 2.15) for XPF-negative patients (interaction P = .35). Neither ERCC1 nor XPF were prognostic: among nonsquamous patients, OS HRs for positive versus negative were ERCC1, 1.11 ( P = .32), and XPF, 1.08 ( P = .55). Conclusion Superior outcomes were observed for patients with squamous histology who received platinum therapy compared with nonplatinum chemotherapy; however, selecting chemotherapy by using commercially available ERCC1 or XPF antibodies did not confer any extra survival benefit.

U2 - 10.1200/JCO.2016.68.1841

DO - 10.1200/JCO.2016.68.1841

M3 - Article

C2 - 27893326

VL - 35

SP - 402

EP - 411

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 4

ER -