Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial

David Ferry; Lucinda Billingham; Hugh Jarrett; David Dunlop; Penella J Woll; Marianne Nicolson; Riyaz Shah; Joyce Thompson; James Spicer; D Muthukumar; Geraldine Skailes; Pauline Leonard; A D Chetiyawardana; Paula Wells; Conrad Lewanski; Barbara Crosse; Michelle Hill; Piers Gaunt; Kenneth O'Byrne

doi:10.1016/j.ejca.2017.05.037

Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial

David Ferry, Lucinda Billingham, Hugh Jarrett, David Dunlop, Penella J Woll, Marianne Nicolson, Riyaz Shah, Joyce Thompson, James Spicer, D Muthukumar, Geraldine Skailes, Pauline Leonard, A D Chetiyawardana, Paula Wells, Conrad Lewanski, Barbara Crosse, Michelle Hill, Piers Gaunt, Kenneth O'Byrne

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Abstract

BACKGROUND: Platinum-based combination chemotherapy is standard treatment for the majority of patients with advanced non-small-cell lung cancer (NSCLC). The trial investigates the importance of the choice of platinum agent and dose of cisplatin in relation to patient outcomes.

METHODS: The three-arm randomised phase III trial assigned patients with chemo-naïve stage IIIB/IV NSCLC in a 1:1:1 ratio to receive gemcitabine 1250 mg/m(2) on days 1 and 8 of a 3-week cycle with cisplatin 80 mg/m(2) (GC80) or cisplatin 50 mg/m(2) (GC50) or carboplatin AUC6 (GCb6) for a maximum of four cycles. Primary outcome measure was survival time, aiming to test for a difference between treatment arms and also assess non-inferiority with pre-defined margin selected as hazard ratio (HR) of 1.2. Secondary outcome measures included response rate, adverse events and quality of life (QoL).

FINDINGS: The trial recruited 1363 patients. Survival time differed significantly across the three treatment arms (p = 0.046) with GC50 worst with median 8.2 months compared to 9.5 for GC80 and 10.0 for GCb6. HRs (adjusted) for GC50 compared to GC80 was 1.13 (95% confidence interval [CI] 0.99-1.29) and for GC50 compared to GCb6 was 1.23 (95% CI: 1.08-1.41). GCb6 was significantly non-inferior to GC80 (HR = 0.93, upper limit of one-sided 95% CI 1.04). Adjusting for QoL did not change the findings. Best objective response rates were 29% (GC80), 20% (GC50) and 27% (GCb6), p < 0.007. There were more dose reductions and treatment delays in the GCb6 arm and more adverse events (60% with at least one grade 3-4 compared to 43% GC80 and 30% GC50).

INTERPRETATION: In combination with gemcitabine, carboplatin at AUC6 is not inferior to cisplatin at 80 mg/m(2) in terms of survival. Carboplatin was associated with more adverse events and not with better quality of life. Cisplatin at the lower dose of 50 mg/m(2) has worse survival which is not compensated by better quality of life. CLINICALTRIALS.

GOV IDENTIFIER: NCT00112710.

EUDRACT NUMBER: 2004-003868-30.

CANCER RESEARCH UK TRIAL IDENTIFIER: CRUK/04/009.

Original language	English
Pages (from-to)	302-312
Number of pages	11
Journal	European Journal of Cancer
Volume	83
Early online date	4 Aug 2017
DOIs	https://doi.org/10.1016/j.ejca.2017.05.037
Publication status	Published - Sept 2017

Keywords

Non-small-cell lung cancer
Carboplatin
Cisplatin
Gemcitabine
Randomised phase III trial
Quality of life

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Stratified Medicine:Methods for Evaluating Predictive Biomarkers for Treatment of Cancer
Billingham, L. (Principal Investigator), Deeks, J. (Co-Investigator), Riley, R. (Co-Investigator), Craddock, C. (Co-Investigator), Middleton, G. (Co-Investigator) & Morton, D. (Co-Investigator)
Cancer Research UK
1/06/14 → 31/05/17
Project: Research

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Ferry, D., Billingham, L., Jarrett, H., Dunlop, D., Woll, P. J., Nicolson, M., Shah, R., Thompson, J., Spicer, J., Muthukumar, D., Skailes, G., Leonard, P., Chetiyawardana, A. D., Wells, P., Lewanski, C., Crosse, B., Hill, M., Gaunt, P., & O'Byrne, K. (2017). Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial. European Journal of Cancer, 83, 302-312. https://doi.org/10.1016/j.ejca.2017.05.037

@article{e23fd99bb3eb4bb5b0c1350c9ecfcfa0,

title = "Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial",

abstract = "BACKGROUND: Platinum-based combination chemotherapy is standard treatment for the majority of patients with advanced non-small-cell lung cancer (NSCLC). The trial investigates the importance of the choice of platinum agent and dose of cisplatin in relation to patient outcomes.METHODS: The three-arm randomised phase III trial assigned patients with chemo-na{\"i}ve stage IIIB/IV NSCLC in a 1:1:1 ratio to receive gemcitabine 1250 mg/m(2) on days 1 and 8 of a 3-week cycle with cisplatin 80 mg/m(2) (GC80) or cisplatin 50 mg/m(2) (GC50) or carboplatin AUC6 (GCb6) for a maximum of four cycles. Primary outcome measure was survival time, aiming to test for a difference between treatment arms and also assess non-inferiority with pre-defined margin selected as hazard ratio (HR) of 1.2. Secondary outcome measures included response rate, adverse events and quality of life (QoL).FINDINGS: The trial recruited 1363 patients. Survival time differed significantly across the three treatment arms (p = 0.046) with GC50 worst with median 8.2 months compared to 9.5 for GC80 and 10.0 for GCb6. HRs (adjusted) for GC50 compared to GC80 was 1.13 (95% confidence interval [CI] 0.99-1.29) and for GC50 compared to GCb6 was 1.23 (95% CI: 1.08-1.41). GCb6 was significantly non-inferior to GC80 (HR = 0.93, upper limit of one-sided 95% CI 1.04). Adjusting for QoL did not change the findings. Best objective response rates were 29% (GC80), 20% (GC50) and 27% (GCb6), p < 0.007. There were more dose reductions and treatment delays in the GCb6 arm and more adverse events (60% with at least one grade 3-4 compared to 43% GC80 and 30% GC50).INTERPRETATION: In combination with gemcitabine, carboplatin at AUC6 is not inferior to cisplatin at 80 mg/m(2) in terms of survival. Carboplatin was associated with more adverse events and not with better quality of life. Cisplatin at the lower dose of 50 mg/m(2) has worse survival which is not compensated by better quality of life. CLINICALTRIALS.GOV IDENTIFIER: NCT00112710.EUDRACT NUMBER: 2004-003868-30.CANCER RESEARCH UK TRIAL IDENTIFIER: CRUK/04/009.",

keywords = "Non-small-cell lung cancer, Carboplatin, Cisplatin, Gemcitabine, Randomised phase III trial, Quality of life",

author = "David Ferry and Lucinda Billingham and Hugh Jarrett and David Dunlop and Woll, {Penella J} and Marianne Nicolson and Riyaz Shah and Joyce Thompson and James Spicer and D Muthukumar and Geraldine Skailes and Pauline Leonard and Chetiyawardana, {A D} and Paula Wells and Conrad Lewanski and Barbara Crosse and Michelle Hill and Piers Gaunt and Kenneth O'Byrne",

year = "2017",

month = sep,

doi = "10.1016/j.ejca.2017.05.037",

language = "English",

volume = "83",

pages = "302--312",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier",

}

Ferry, D, Billingham, L, Jarrett, H, Dunlop, D, Woll, PJ, Nicolson, M, Shah, R, Thompson, J, Spicer, J, Muthukumar, D, Skailes, G, Leonard, P, Chetiyawardana, AD, Wells, P, Lewanski, C, Crosse, B, Hill, M, Gaunt, P & O'Byrne, K 2017, 'Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial', European Journal of Cancer, vol. 83, pp. 302-312. https://doi.org/10.1016/j.ejca.2017.05.037

Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial. / Ferry, David; Billingham, Lucinda; Jarrett, Hugh et al.
In: European Journal of Cancer, Vol. 83, 09.2017, p. 302-312.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer

T2 - results from a British Thoracic Oncology Group randomised phase III trial

AU - Ferry, David

AU - Billingham, Lucinda

AU - Jarrett, Hugh

AU - Dunlop, David

AU - Woll, Penella J

AU - Nicolson, Marianne

AU - Shah, Riyaz

AU - Thompson, Joyce

AU - Spicer, James

AU - Muthukumar, D

AU - Skailes, Geraldine

AU - Leonard, Pauline

AU - Chetiyawardana, A D

AU - Wells, Paula

AU - Lewanski, Conrad

AU - Crosse, Barbara

AU - Hill, Michelle

AU - Gaunt, Piers

AU - O'Byrne, Kenneth

PY - 2017/9

Y1 - 2017/9

N2 - BACKGROUND: Platinum-based combination chemotherapy is standard treatment for the majority of patients with advanced non-small-cell lung cancer (NSCLC). The trial investigates the importance of the choice of platinum agent and dose of cisplatin in relation to patient outcomes.METHODS: The three-arm randomised phase III trial assigned patients with chemo-naïve stage IIIB/IV NSCLC in a 1:1:1 ratio to receive gemcitabine 1250 mg/m(2) on days 1 and 8 of a 3-week cycle with cisplatin 80 mg/m(2) (GC80) or cisplatin 50 mg/m(2) (GC50) or carboplatin AUC6 (GCb6) for a maximum of four cycles. Primary outcome measure was survival time, aiming to test for a difference between treatment arms and also assess non-inferiority with pre-defined margin selected as hazard ratio (HR) of 1.2. Secondary outcome measures included response rate, adverse events and quality of life (QoL).FINDINGS: The trial recruited 1363 patients. Survival time differed significantly across the three treatment arms (p = 0.046) with GC50 worst with median 8.2 months compared to 9.5 for GC80 and 10.0 for GCb6. HRs (adjusted) for GC50 compared to GC80 was 1.13 (95% confidence interval [CI] 0.99-1.29) and for GC50 compared to GCb6 was 1.23 (95% CI: 1.08-1.41). GCb6 was significantly non-inferior to GC80 (HR = 0.93, upper limit of one-sided 95% CI 1.04). Adjusting for QoL did not change the findings. Best objective response rates were 29% (GC80), 20% (GC50) and 27% (GCb6), p < 0.007. There were more dose reductions and treatment delays in the GCb6 arm and more adverse events (60% with at least one grade 3-4 compared to 43% GC80 and 30% GC50).INTERPRETATION: In combination with gemcitabine, carboplatin at AUC6 is not inferior to cisplatin at 80 mg/m(2) in terms of survival. Carboplatin was associated with more adverse events and not with better quality of life. Cisplatin at the lower dose of 50 mg/m(2) has worse survival which is not compensated by better quality of life. CLINICALTRIALS.GOV IDENTIFIER: NCT00112710.EUDRACT NUMBER: 2004-003868-30.CANCER RESEARCH UK TRIAL IDENTIFIER: CRUK/04/009.

AB - BACKGROUND: Platinum-based combination chemotherapy is standard treatment for the majority of patients with advanced non-small-cell lung cancer (NSCLC). The trial investigates the importance of the choice of platinum agent and dose of cisplatin in relation to patient outcomes.METHODS: The three-arm randomised phase III trial assigned patients with chemo-naïve stage IIIB/IV NSCLC in a 1:1:1 ratio to receive gemcitabine 1250 mg/m(2) on days 1 and 8 of a 3-week cycle with cisplatin 80 mg/m(2) (GC80) or cisplatin 50 mg/m(2) (GC50) or carboplatin AUC6 (GCb6) for a maximum of four cycles. Primary outcome measure was survival time, aiming to test for a difference between treatment arms and also assess non-inferiority with pre-defined margin selected as hazard ratio (HR) of 1.2. Secondary outcome measures included response rate, adverse events and quality of life (QoL).FINDINGS: The trial recruited 1363 patients. Survival time differed significantly across the three treatment arms (p = 0.046) with GC50 worst with median 8.2 months compared to 9.5 for GC80 and 10.0 for GCb6. HRs (adjusted) for GC50 compared to GC80 was 1.13 (95% confidence interval [CI] 0.99-1.29) and for GC50 compared to GCb6 was 1.23 (95% CI: 1.08-1.41). GCb6 was significantly non-inferior to GC80 (HR = 0.93, upper limit of one-sided 95% CI 1.04). Adjusting for QoL did not change the findings. Best objective response rates were 29% (GC80), 20% (GC50) and 27% (GCb6), p < 0.007. There were more dose reductions and treatment delays in the GCb6 arm and more adverse events (60% with at least one grade 3-4 compared to 43% GC80 and 30% GC50).INTERPRETATION: In combination with gemcitabine, carboplatin at AUC6 is not inferior to cisplatin at 80 mg/m(2) in terms of survival. Carboplatin was associated with more adverse events and not with better quality of life. Cisplatin at the lower dose of 50 mg/m(2) has worse survival which is not compensated by better quality of life. CLINICALTRIALS.GOV IDENTIFIER: NCT00112710.EUDRACT NUMBER: 2004-003868-30.CANCER RESEARCH UK TRIAL IDENTIFIER: CRUK/04/009.

KW - Non-small-cell lung cancer

KW - Carboplatin

KW - Cisplatin

KW - Gemcitabine

KW - Randomised phase III trial

KW - Quality of life

U2 - 10.1016/j.ejca.2017.05.037

DO - 10.1016/j.ejca.2017.05.037

M3 - Article

C2 - 28780466

SN - 0959-8049

VL - 83

SP - 302

EP - 312

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Ferry D, Billingham L, Jarrett H, Dunlop D, Woll PJ, Nicolson M et al. Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial. European Journal of Cancer. 2017 Sept;83:302-312. Epub 2017 Aug 4. doi: 10.1016/j.ejca.2017.05.037

Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial

Abstract

Keywords

UN SDGs

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Projects

Stratified Medicine:Methods for Evaluating Predictive Biomarkers for Treatment of Cancer

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