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. MencoboniF. Nelli, F. Riccardi, G. Di Isernia, R. Costanzo, G. Rocco, G. Daniele, S. Signoriello, M.C. Piccirillo, C. Gallo, F. Perrone

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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
Issue number25
Publication statusPublished - Sep 1 2018


  • 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


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