The effect on QOL of adding platinum to first line treatment of elderly patients (pts) with advanced NSCLC is unknown. In this setting, MILES-3 and MILES-4 trials prospectively showed that adding cisplatin (Cis) to single-agent gemcitabine (Gem) or pemetrexed (Pem) does not significantly prolong overall survival.
Advanced NSCLC pts, >70 years old, ECOG performance status 0-1, were eligible. In MILES-3, pts with any tumor histology were randomly assigned to CisGem or Gem. In MILES-4, pts with non-squamous histology were randomly assigned to CisGem, Gem, CisPem or Pem. The trials were joined together because of slow accrual. Overall survival was the primary endpoint. QOL (EORTC QLQ C30 and LC13) was a secondary endpoint. Five questionnaires were planned in MILES-3 and 7 in MILES-4; QOL was measured in both the trials at 3 time points (baseline, end cycle 1, end cycle 2) used for joint analysis. Intention-to-treat strategy was applied; analyses were adjusted for baseline QOL, stage, PS, gender, age, size of centre, trial, histotype and companion drug.
Overall, 458/531 pts (86.3%) answered baseline questionnaire. Rate of missing questionnaires at end cycle 1 and 2 was slightly higher among pts receiving Cis. Mean change in fatigue after cycle 1 (P = 0.01) and in sore mouth after cycle 2 (P = 0.02) were worse with Cis. Using a 10% change from baseline as clinically relevant threshold to categorize response, alopecia was significantly worse with Cis (P = 0.05). In time to deterioration analysis with progression/death as competitive risk, sore mouth and alopecia deteriorated more with Cis (HR 1.72 95%CI 1.02-2.89 P = 0.04 and HR 1.84 95%CI 1.09-3.10, P = 0.02, respectively). Response analysis in MILES-3 confirmed findings of the joint analysis while time to deterioration analysis in MILES-4 did not find any significant difference. Cis did not significantly improve any QOL item, in any type of analysis.
The addition of Cisplatin did not improve QOL of elderly patients with advanced NSCLC. Partially supported by AIFA (grant FARM8KAJZK) and Eli Lilly.
Clinical trial identification
MILES 3 EudraCT number: 2009 − 013540−36 MILES 4 EudraCT number: 2012-000164-25
Legal entity responsible for the study
Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale
M.C. Piccirillo: Received honoraria by Bayer for consulting and travel payment by Roche and Bayer for congresses. A. Morabito: Consulting or Advisory Role for Bristol-Myers Squibb and that received Honoraria by Roche, Boehringer Ingelheim, AstraZeneca, Lilly, Bayer, Italfarmaco and Pfizer. P. Maione: Honoraria by Lilly, Boehringer Ingelheim, AsaraZeneca and Roche, and that had Consulting or Advisory Role for Lilly, Boehringer Ingelheim, AsaraZeneca, Roche. F. Perrone: Received Travel, Accommodations, Expenses by Roche, Lilly, Bayer, Daiichi Sankyo, and received Honoraria by Amgen, Novartis, Lilly, Roche, Bayer, Daiichi Sankyo, and that his Institution had Research Funding from Roche, Bayer. C. Gridelli: Consulting Role for MSD, BMS, Celgene, Novartis, Roche, had Speakers\' Bureau from BMS, MSD, Celgene, Novartis, Roche, had Research Funding from Lilly, received Travel Expenses by MSD, BMS, Celgene, Novartis All other authors have declared no conflicts of interest.