Adjuvant chemotherapy for resected early-stage non-small cell lung cancer

Sarah Burdett, Jean P ierre Pignon, Jayne Tierney, Helene Tribodet, Lesley Stewart, Cecile Le Pechoux, Anne Aupérin, Thierry Le Chevalier, Richard J. Stephens, Rodrigo Arriagada, Julian P T Higgins, David H. Johnson, Jan Van Meerbeeck, Mahesh K B Parmar, Robert L. Souhami, Bengt Bergman, Jean Yves Douillard, Ariane Dunant, Chiaki Endo, David Girling & 20 others Harubumi Kato, Steven M. Keller, Hideki Kimura, Aija Knuuttila, Ken Kodama, Ritsuko Komaki, Mark G. Kris, Thomas Lad, Tommaso Mineo, Steven Piantadosi, Rafael Rosell, Giorgio Scagliotti, Lesley K. Seymour, Frances A. Shepherd, Richard Sylvester, Hirohito Tada, Fumihiro Tanaka, Valter Torri, David Waller, Ying Liang

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

BACKGROUND: To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC),we performed two systematic reviews and meta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010.

OBJECTIVES: To compare, in terms of overall survival, time to locoregional recurrence, time to distant recurrence and recurrence-free survival:A. Surgery versus surgery plus adjuvant chemotherapyB. Surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapyin patients with histologically diagnosed early stage NSCLC.(2)To investigate whether or not predefined patient subgroups benefit more or less from cisplatin-based chemotherapy in terms of survival.

SEARCH METHODS: We supplemented MEDLINE and CANCERLIT searches (1995 to December 2013) with information from trial registers, handsearching relevant meeting proceedings and by discussion with trialists and organisations.

SELECTION CRITERIA: We included trials of a) surgery versus surgery plus adjuvant chemotherapy; and b) surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy, provided that they randomised NSCLC patients using a method which precluded prior knowledge of treatment assignment.

DATA COLLECTION AND ANALYSIS: We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. Data from all patients were sought from those responsible for the trial. We obtained updated individual participant data (IPD) on survival, and date of last follow-up, as well as details of treatment allocated, date of randomisation, age, sex, histological cell type, stage, and performance status. To avoid potential bias, we requested information for all randomised patients, including those excluded from the investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. For trials using cisplatin-based regimens, we carried out subgroup analyses by age, sex, histological cell type, tumour stage, and performance status.

MAIN RESULTS: We identified 35 trials evaluating surgery plus adjuvant chemotherapy versus surgery alone. IPD were available for 26 of these trials and our analyses are based on 8447 participants (3323 deaths) in 34 trial comparisons. There was clear evidence of a benefit of adding chemotherapy after surgery (hazard ratio (HR)= 0.86, 95% confidence interval (CI)= 0.81 to 0.92, p<0.0001), with an absolute increase in survival of 4% at five years.We identified 15 trials evaluating surgery plus radiotherapy plus chemotherapy versus surgery plus radiotherapy alone. IPD were available for 12 of these trials and our analyses are based on 2660 participants (1909 deaths) in 13 trial comparisons. There was also evidence of a benefit of adding chemotherapy to surgery plus radiotherapy (HR= 0.88, 95% CI= 0.81 to 0.97, p= 0.009). This represents an absolute improvement in survival of 4% at five years.For both meta-analyses, we found similar benefits for recurrence outcomes and there was little variation in effect according to the type of chemotherapy, other trial characteristics or patient subgroup.We did not undertake analysis of the effects of adjuvant chemotherapy on quality of life and adverse events. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable. We considered the risk of bias in the included trials to be low.

AUTHORS' CONCLUSIONS: Results from 47 trial comparisons and 11,107 patients demonstrate the clear benefit of adjuvant chemotherapy for these patients, irrespective of whether chemotherapy was given in addition to surgery or surgery plus radiotherapy. This is the most up-to-date and complete systematic review and individual participant data (IPD) meta-analysis that has been carried out.

Original languageEnglish (US)
Pages (from-to)CD011430
JournalCochrane database of systematic reviews (Online)
Volume3
DOIs
StatePublished - 2015
Externally publishedYes

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Adjuvant Chemotherapy
Non-Small Cell Lung Carcinoma
Radiotherapy
Drug Therapy
Survival
Meta-Analysis
Recurrence
Cisplatin
Quality of Life
Confidence Intervals
Adjuvant Radiotherapy
Intention to Treat Analysis
Random Allocation
MEDLINE

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Burdett, S., Pignon, J. P. I., Tierney, J., Tribodet, H., Stewart, L., Le Pechoux, C., ... Liang, Y. (2015). Adjuvant chemotherapy for resected early-stage non-small cell lung cancer. Cochrane database of systematic reviews (Online), 3, CD011430. https://doi.org/10.1002/14651858.CD011430

Adjuvant chemotherapy for resected early-stage non-small cell lung cancer. / Burdett, Sarah; Pignon, Jean P ierre; Tierney, Jayne; Tribodet, Helene; Stewart, Lesley; Le Pechoux, Cecile; Aupérin, Anne; Le Chevalier, Thierry; Stephens, Richard J.; Arriagada, Rodrigo; Higgins, Julian P T; Johnson, David H.; Van Meerbeeck, Jan; Parmar, Mahesh K B; Souhami, Robert L.; Bergman, Bengt; Douillard, Jean Yves; Dunant, Ariane; Endo, Chiaki; Girling, David; Kato, Harubumi; Keller, Steven M.; Kimura, Hideki; Knuuttila, Aija; Kodama, Ken; Komaki, Ritsuko; Kris, Mark G.; Lad, Thomas; Mineo, Tommaso; Piantadosi, Steven; Rosell, Rafael; Scagliotti, Giorgio; Seymour, Lesley K.; Shepherd, Frances A.; Sylvester, Richard; Tada, Hirohito; Tanaka, Fumihiro; Torri, Valter; Waller, David; Liang, Ying.

In: Cochrane database of systematic reviews (Online), Vol. 3, 2015, p. CD011430.

Research output: Contribution to journalArticle

Burdett, S, Pignon, JPI, Tierney, J, Tribodet, H, Stewart, L, Le Pechoux, C, Aupérin, A, Le Chevalier, T, Stephens, RJ, Arriagada, R, Higgins, JPT, Johnson, DH, Van Meerbeeck, J, Parmar, MKB, Souhami, RL, Bergman, B, Douillard, JY, Dunant, A, Endo, C, Girling, D, Kato, H, Keller, SM, Kimura, H, Knuuttila, A, Kodama, K, Komaki, R, Kris, MG, Lad, T, Mineo, T, Piantadosi, S, Rosell, R, Scagliotti, G, Seymour, LK, Shepherd, FA, Sylvester, R, Tada, H, Tanaka, F, Torri, V, Waller, D & Liang, Y 2015, 'Adjuvant chemotherapy for resected early-stage non-small cell lung cancer', Cochrane database of systematic reviews (Online), vol. 3, pp. CD011430. https://doi.org/10.1002/14651858.CD011430
Burdett, Sarah ; Pignon, Jean P ierre ; Tierney, Jayne ; Tribodet, Helene ; Stewart, Lesley ; Le Pechoux, Cecile ; Aupérin, Anne ; Le Chevalier, Thierry ; Stephens, Richard J. ; Arriagada, Rodrigo ; Higgins, Julian P T ; Johnson, David H. ; Van Meerbeeck, Jan ; Parmar, Mahesh K B ; Souhami, Robert L. ; Bergman, Bengt ; Douillard, Jean Yves ; Dunant, Ariane ; Endo, Chiaki ; Girling, David ; Kato, Harubumi ; Keller, Steven M. ; Kimura, Hideki ; Knuuttila, Aija ; Kodama, Ken ; Komaki, Ritsuko ; Kris, Mark G. ; Lad, Thomas ; Mineo, Tommaso ; Piantadosi, Steven ; Rosell, Rafael ; Scagliotti, Giorgio ; Seymour, Lesley K. ; Shepherd, Frances A. ; Sylvester, Richard ; Tada, Hirohito ; Tanaka, Fumihiro ; Torri, Valter ; Waller, David ; Liang, Ying. / Adjuvant chemotherapy for resected early-stage non-small cell lung cancer. In: Cochrane database of systematic reviews (Online). 2015 ; Vol. 3. pp. CD011430.
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title = "Adjuvant chemotherapy for resected early-stage non-small cell lung cancer",
abstract = "BACKGROUND: To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC),we performed two systematic reviews and meta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010.OBJECTIVES: To compare, in terms of overall survival, time to locoregional recurrence, time to distant recurrence and recurrence-free survival:A. Surgery versus surgery plus adjuvant chemotherapyB. Surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapyin patients with histologically diagnosed early stage NSCLC.(2)To investigate whether or not predefined patient subgroups benefit more or less from cisplatin-based chemotherapy in terms of survival.SEARCH METHODS: We supplemented MEDLINE and CANCERLIT searches (1995 to December 2013) with information from trial registers, handsearching relevant meeting proceedings and by discussion with trialists and organisations.SELECTION CRITERIA: We included trials of a) surgery versus surgery plus adjuvant chemotherapy; and b) surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy, provided that they randomised NSCLC patients using a method which precluded prior knowledge of treatment assignment.DATA COLLECTION AND ANALYSIS: We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. Data from all patients were sought from those responsible for the trial. We obtained updated individual participant data (IPD) on survival, and date of last follow-up, as well as details of treatment allocated, date of randomisation, age, sex, histological cell type, stage, and performance status. To avoid potential bias, we requested information for all randomised patients, including those excluded from the investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. For trials using cisplatin-based regimens, we carried out subgroup analyses by age, sex, histological cell type, tumour stage, and performance status.MAIN RESULTS: We identified 35 trials evaluating surgery plus adjuvant chemotherapy versus surgery alone. IPD were available for 26 of these trials and our analyses are based on 8447 participants (3323 deaths) in 34 trial comparisons. There was clear evidence of a benefit of adding chemotherapy after surgery (hazard ratio (HR)= 0.86, 95{\%} confidence interval (CI)= 0.81 to 0.92, p<0.0001), with an absolute increase in survival of 4{\%} at five years.We identified 15 trials evaluating surgery plus radiotherapy plus chemotherapy versus surgery plus radiotherapy alone. IPD were available for 12 of these trials and our analyses are based on 2660 participants (1909 deaths) in 13 trial comparisons. There was also evidence of a benefit of adding chemotherapy to surgery plus radiotherapy (HR= 0.88, 95{\%} CI= 0.81 to 0.97, p= 0.009). This represents an absolute improvement in survival of 4{\%} at five years.For both meta-analyses, we found similar benefits for recurrence outcomes and there was little variation in effect according to the type of chemotherapy, other trial characteristics or patient subgroup.We did not undertake analysis of the effects of adjuvant chemotherapy on quality of life and adverse events. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable. We considered the risk of bias in the included trials to be low.AUTHORS' CONCLUSIONS: Results from 47 trial comparisons and 11,107 patients demonstrate the clear benefit of adjuvant chemotherapy for these patients, irrespective of whether chemotherapy was given in addition to surgery or surgery plus radiotherapy. This is the most up-to-date and complete systematic review and individual participant data (IPD) meta-analysis that has been carried out.",
author = "Sarah Burdett and Pignon, {Jean P ierre} and Jayne Tierney and Helene Tribodet and Lesley Stewart and {Le Pechoux}, Cecile and Anne Aup{\'e}rin and {Le Chevalier}, Thierry and Stephens, {Richard J.} and Rodrigo Arriagada and Higgins, {Julian P T} and Johnson, {David H.} and {Van Meerbeeck}, Jan and Parmar, {Mahesh K B} and Souhami, {Robert L.} and Bengt Bergman and Douillard, {Jean Yves} and Ariane Dunant and Chiaki Endo and David Girling and Harubumi Kato and Keller, {Steven M.} and Hideki Kimura and Aija Knuuttila and Ken Kodama and Ritsuko Komaki and Kris, {Mark G.} and Thomas Lad and Tommaso Mineo and Steven Piantadosi and Rafael Rosell and Giorgio Scagliotti and Seymour, {Lesley K.} and Shepherd, {Frances A.} and Richard Sylvester and Hirohito Tada and Fumihiro Tanaka and Valter Torri and David Waller and Ying Liang",
year = "2015",
doi = "10.1002/14651858.CD011430",
language = "English (US)",
volume = "3",
pages = "CD011430",
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TY - JOUR

T1 - Adjuvant chemotherapy for resected early-stage non-small cell lung cancer

AU - Burdett, Sarah

AU - Pignon, Jean P ierre

AU - Tierney, Jayne

AU - Tribodet, Helene

AU - Stewart, Lesley

AU - Le Pechoux, Cecile

AU - Aupérin, Anne

AU - Le Chevalier, Thierry

AU - Stephens, Richard J.

AU - Arriagada, Rodrigo

AU - Higgins, Julian P T

AU - Johnson, David H.

AU - Van Meerbeeck, Jan

AU - Parmar, Mahesh K B

AU - Souhami, Robert L.

AU - Bergman, Bengt

AU - Douillard, Jean Yves

AU - Dunant, Ariane

AU - Endo, Chiaki

AU - Girling, David

AU - Kato, Harubumi

AU - Keller, Steven M.

AU - Kimura, Hideki

AU - Knuuttila, Aija

AU - Kodama, Ken

AU - Komaki, Ritsuko

AU - Kris, Mark G.

AU - Lad, Thomas

AU - Mineo, Tommaso

AU - Piantadosi, Steven

AU - Rosell, Rafael

AU - Scagliotti, Giorgio

AU - Seymour, Lesley K.

AU - Shepherd, Frances A.

AU - Sylvester, Richard

AU - Tada, Hirohito

AU - Tanaka, Fumihiro

AU - Torri, Valter

AU - Waller, David

AU - Liang, Ying

PY - 2015

Y1 - 2015

N2 - BACKGROUND: To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC),we performed two systematic reviews and meta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010.OBJECTIVES: To compare, in terms of overall survival, time to locoregional recurrence, time to distant recurrence and recurrence-free survival:A. Surgery versus surgery plus adjuvant chemotherapyB. Surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapyin patients with histologically diagnosed early stage NSCLC.(2)To investigate whether or not predefined patient subgroups benefit more or less from cisplatin-based chemotherapy in terms of survival.SEARCH METHODS: We supplemented MEDLINE and CANCERLIT searches (1995 to December 2013) with information from trial registers, handsearching relevant meeting proceedings and by discussion with trialists and organisations.SELECTION CRITERIA: We included trials of a) surgery versus surgery plus adjuvant chemotherapy; and b) surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy, provided that they randomised NSCLC patients using a method which precluded prior knowledge of treatment assignment.DATA COLLECTION AND ANALYSIS: We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. Data from all patients were sought from those responsible for the trial. We obtained updated individual participant data (IPD) on survival, and date of last follow-up, as well as details of treatment allocated, date of randomisation, age, sex, histological cell type, stage, and performance status. To avoid potential bias, we requested information for all randomised patients, including those excluded from the investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. For trials using cisplatin-based regimens, we carried out subgroup analyses by age, sex, histological cell type, tumour stage, and performance status.MAIN RESULTS: We identified 35 trials evaluating surgery plus adjuvant chemotherapy versus surgery alone. IPD were available for 26 of these trials and our analyses are based on 8447 participants (3323 deaths) in 34 trial comparisons. There was clear evidence of a benefit of adding chemotherapy after surgery (hazard ratio (HR)= 0.86, 95% confidence interval (CI)= 0.81 to 0.92, p<0.0001), with an absolute increase in survival of 4% at five years.We identified 15 trials evaluating surgery plus radiotherapy plus chemotherapy versus surgery plus radiotherapy alone. IPD were available for 12 of these trials and our analyses are based on 2660 participants (1909 deaths) in 13 trial comparisons. There was also evidence of a benefit of adding chemotherapy to surgery plus radiotherapy (HR= 0.88, 95% CI= 0.81 to 0.97, p= 0.009). This represents an absolute improvement in survival of 4% at five years.For both meta-analyses, we found similar benefits for recurrence outcomes and there was little variation in effect according to the type of chemotherapy, other trial characteristics or patient subgroup.We did not undertake analysis of the effects of adjuvant chemotherapy on quality of life and adverse events. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable. We considered the risk of bias in the included trials to be low.AUTHORS' CONCLUSIONS: Results from 47 trial comparisons and 11,107 patients demonstrate the clear benefit of adjuvant chemotherapy for these patients, irrespective of whether chemotherapy was given in addition to surgery or surgery plus radiotherapy. This is the most up-to-date and complete systematic review and individual participant data (IPD) meta-analysis that has been carried out.

AB - BACKGROUND: To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC),we performed two systematic reviews and meta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010.OBJECTIVES: To compare, in terms of overall survival, time to locoregional recurrence, time to distant recurrence and recurrence-free survival:A. Surgery versus surgery plus adjuvant chemotherapyB. Surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapyin patients with histologically diagnosed early stage NSCLC.(2)To investigate whether or not predefined patient subgroups benefit more or less from cisplatin-based chemotherapy in terms of survival.SEARCH METHODS: We supplemented MEDLINE and CANCERLIT searches (1995 to December 2013) with information from trial registers, handsearching relevant meeting proceedings and by discussion with trialists and organisations.SELECTION CRITERIA: We included trials of a) surgery versus surgery plus adjuvant chemotherapy; and b) surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy, provided that they randomised NSCLC patients using a method which precluded prior knowledge of treatment assignment.DATA COLLECTION AND ANALYSIS: We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. Data from all patients were sought from those responsible for the trial. We obtained updated individual participant data (IPD) on survival, and date of last follow-up, as well as details of treatment allocated, date of randomisation, age, sex, histological cell type, stage, and performance status. To avoid potential bias, we requested information for all randomised patients, including those excluded from the investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. For trials using cisplatin-based regimens, we carried out subgroup analyses by age, sex, histological cell type, tumour stage, and performance status.MAIN RESULTS: We identified 35 trials evaluating surgery plus adjuvant chemotherapy versus surgery alone. IPD were available for 26 of these trials and our analyses are based on 8447 participants (3323 deaths) in 34 trial comparisons. There was clear evidence of a benefit of adding chemotherapy after surgery (hazard ratio (HR)= 0.86, 95% confidence interval (CI)= 0.81 to 0.92, p<0.0001), with an absolute increase in survival of 4% at five years.We identified 15 trials evaluating surgery plus radiotherapy plus chemotherapy versus surgery plus radiotherapy alone. IPD were available for 12 of these trials and our analyses are based on 2660 participants (1909 deaths) in 13 trial comparisons. There was also evidence of a benefit of adding chemotherapy to surgery plus radiotherapy (HR= 0.88, 95% CI= 0.81 to 0.97, p= 0.009). This represents an absolute improvement in survival of 4% at five years.For both meta-analyses, we found similar benefits for recurrence outcomes and there was little variation in effect according to the type of chemotherapy, other trial characteristics or patient subgroup.We did not undertake analysis of the effects of adjuvant chemotherapy on quality of life and adverse events. Quality of life information was not routinely collected during the trials, but where toxicity was assessed and mentioned in the publications, it was thought to be manageable. We considered the risk of bias in the included trials to be low.AUTHORS' CONCLUSIONS: Results from 47 trial comparisons and 11,107 patients demonstrate the clear benefit of adjuvant chemotherapy for these patients, irrespective of whether chemotherapy was given in addition to surgery or surgery plus radiotherapy. This is the most up-to-date and complete systematic review and individual participant data (IPD) meta-analysis that has been carried out.

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U2 - 10.1002/14651858.CD011430

DO - 10.1002/14651858.CD011430

M3 - Article

VL - 3

SP - CD011430

JO - Cochrane database of systematic reviews (Online)

JF - Cochrane database of systematic reviews (Online)

SN - 1361-6137

ER -