Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: Joint analysis of MILES-3 and MILES-4 phase III trials

C. Gridelli, A. Morabito, L. Cavanna, A. Luciani, P. Maione, L. Bonanno, V. Filipazzi, S. Leo, S. Cinieri, F. Ciardiello, M.A. Burgio, D. Bilancia, D. Cortinovis, F. Rosetti, R. Bianco, V. Gebbia, F. Artioli, R. Bordonaro, V. Fregoni, M. Mencoboni & 10 others F. Nelli, F. Riccardi, G. Di Isernia, R. Costanzo, G. Rocco, G. Daniele, S. Signoriello, M.C. Piccirillo, C. Gallo, F. Perrone

Research output: Contribution to journalArticle

Abstract

Purpose: To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods: Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed a of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results: From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion: The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC. © 2018 by American Society of Clinical Oncology
Original languageEnglish
Pages (from-to)2585-2592
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number25
DOIs
Publication statusPublished - Sep 1 2018

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Non-Small Cell Lung Carcinoma
Cisplatin
gemcitabine
Pemetrexed
Therapeutics
Health Status
Disease-Free Survival
Quality of Life
Survival
Anorexia
Fatigue
Histology
Joints
Databases
Drug Therapy
Pharmaceutical Preparations

Keywords

  • cisplatin
  • cyanocobalamin
  • dexamethasone
  • folic acid
  • gemcitabine
  • pemetrexed, advanced cancer
  • adverse drug reaction
  • age
  • aged
  • anemia
  • anorexia
  • Article
  • blood toxicity
  • cancer combination chemotherapy
  • cancer staging
  • clinical practice
  • constipation
  • controlled study
  • coughing
  • daily life activity
  • diarrhea
  • drug efficacy
  • dyspnea
  • fatigue
  • febrile neutropenia
  • female
  • fever
  • follow up
  • heart disease
  • human
  • hyperglycemia
  • leukopenia
  • major clinical study
  • male
  • mucosa inflammation
  • multicenter study
  • multiple cycle treatment
  • nausea
  • neutropenia
  • non small cell lung cancer
  • open study
  • overall survival
  • paresthesia
  • patient compliance
  • phase 3 clinical trial
  • priority journal
  • progression free survival
  • quality of life
  • randomized controlled trial
  • response evaluation criteria in solid tumors
  • senescence
  • sex
  • skin disease
  • stomach pain
  • survival rate
  • very elderly
  • vomiting

Cite this

Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: Joint analysis of MILES-3 and MILES-4 phase III trials. / Gridelli, C.; Morabito, A.; Cavanna, L.; Luciani, A.; Maione, P.; Bonanno, L.; Filipazzi, V.; Leo, S.; Cinieri, S.; Ciardiello, F.; Burgio, M.A.; Bilancia, D.; Cortinovis, D.; Rosetti, F.; Bianco, R.; Gebbia, V.; Artioli, F.; Bordonaro, R.; Fregoni, V.; Mencoboni, M.; Nelli, F.; Riccardi, F.; Di Isernia, G.; Costanzo, R.; Rocco, G.; Daniele, G.; Signoriello, S.; Piccirillo, M.C.; Gallo, C.; Perrone, F.

In: Journal of Clinical Oncology, Vol. 36, No. 25, 01.09.2018, p. 2585-2592.

Research output: Contribution to journalArticle

Gridelli, C, Morabito, A, Cavanna, L, Luciani, A, Maione, P, Bonanno, L, Filipazzi, V, Leo, S, Cinieri, S, Ciardiello, F, Burgio, MA, Bilancia, D, Cortinovis, D, Rosetti, F, Bianco, R, Gebbia, V, Artioli, F, Bordonaro, R, Fregoni, V, Mencoboni, M, Nelli, F, Riccardi, F, Di Isernia, G, Costanzo, R, Rocco, G, Daniele, G, Signoriello, S, Piccirillo, MC, Gallo, C & Perrone, F 2018, 'Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: Joint analysis of MILES-3 and MILES-4 phase III trials', Journal of Clinical Oncology, vol. 36, no. 25, pp. 2585-2592. https://doi.org/10.1200/JCO.2017.76.8390
Gridelli, C. ; Morabito, A. ; Cavanna, L. ; Luciani, A. ; Maione, P. ; Bonanno, L. ; Filipazzi, V. ; Leo, S. ; Cinieri, S. ; Ciardiello, F. ; Burgio, M.A. ; Bilancia, D. ; Cortinovis, D. ; Rosetti, F. ; Bianco, R. ; Gebbia, V. ; Artioli, F. ; Bordonaro, R. ; Fregoni, V. ; Mencoboni, M. ; Nelli, F. ; Riccardi, F. ; Di Isernia, G. ; Costanzo, R. ; Rocco, G. ; Daniele, G. ; Signoriello, S. ; Piccirillo, M.C. ; Gallo, C. ; Perrone, F. / Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: Joint analysis of MILES-3 and MILES-4 phase III trials. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 25. pp. 2585-2592.
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title = "Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: Joint analysis of MILES-3 and MILES-4 phase III trials",
abstract = "Purpose: To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods: Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80{\%} power and two-tailed a of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results: From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79{\%} were male, and 70{\%} had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95{\%} CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95{\%} CI, 0.63 to 0.92; P = .005) and objective response rate (15.5{\%} v 8.5{\%}; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion: The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC. {\circledC} 2018 by American Society of Clinical Oncology",
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TY - JOUR

T1 - Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: Joint analysis of MILES-3 and MILES-4 phase III trials

AU - Gridelli, C.

AU - Morabito, A.

AU - Cavanna, L.

AU - Luciani, A.

AU - Maione, P.

AU - Bonanno, L.

AU - Filipazzi, V.

AU - Leo, S.

AU - Cinieri, S.

AU - Ciardiello, F.

AU - Burgio, M.A.

AU - Bilancia, D.

AU - Cortinovis, D.

AU - Rosetti, F.

AU - Bianco, R.

AU - Gebbia, V.

AU - Artioli, F.

AU - Bordonaro, R.

AU - Fregoni, V.

AU - Mencoboni, M.

AU - Nelli, F.

AU - Riccardi, F.

AU - Di Isernia, G.

AU - Costanzo, R.

AU - Rocco, G.

AU - Daniele, G.

AU - Signoriello, S.

AU - Piccirillo, M.C.

AU - Gallo, C.

AU - Perrone, F.

N1 - cited By 3

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Purpose: To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods: Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed a of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results: From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion: The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC. © 2018 by American Society of Clinical Oncology

AB - Purpose: To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and Methods: Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed a of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results: From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion: The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC. © 2018 by American Society of Clinical Oncology

KW - cisplatin

KW - cyanocobalamin

KW - dexamethasone

KW - folic acid

KW - gemcitabine

KW - pemetrexed, advanced cancer

KW - adverse drug reaction

KW - age

KW - aged

KW - anemia

KW - anorexia

KW - Article

KW - blood toxicity

KW - cancer combination chemotherapy

KW - cancer staging

KW - clinical practice

KW - constipation

KW - controlled study

KW - coughing

KW - daily life activity

KW - diarrhea

KW - drug efficacy

KW - dyspnea

KW - fatigue

KW - febrile neutropenia

KW - female

KW - fever

KW - follow up

KW - heart disease

KW - human

KW - hyperglycemia

KW - leukopenia

KW - major clinical study

KW - male

KW - mucosa inflammation

KW - multicenter study

KW - multiple cycle treatment

KW - nausea

KW - neutropenia

KW - non small cell lung cancer

KW - open study

KW - overall survival

KW - paresthesia

KW - patient compliance

KW - phase 3 clinical trial

KW - priority journal

KW - progression free survival

KW - quality of life

KW - randomized controlled trial

KW - response evaluation criteria in solid tumors

KW - senescence

KW - sex

KW - skin disease

KW - stomach pain

KW - survival rate

KW - very elderly

KW - vomiting

U2 - 10.1200/JCO.2017.76.8390

DO - 10.1200/JCO.2017.76.8390

M3 - Article

VL - 36

SP - 2585

EP - 2592

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 25

ER -