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 α 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.

<p>MiR-140 Resensitizes Cisplatin-Resistant NSCLC Cells to Cisplatin Treatment Through the SIRT1/ROS/JNK Pathway</p>

“…Cisplatin-based chemotherapy is considered as the first-line treatment for NSCLC. 13 , 14 Despite cisplatin-based chemotherapy is effective, development of drug resistance is a usual incidence during the course of cisplatin treatment. 15 , 16 It is urgent for us to explore useful approaches to reverse the resistance against cisplatin.…”

“… 11 , 12 Nowadays, cisplatin-based chemotherapy is still used as the first-line treatment for NSCLC. 13 , 14 However, virtually all of the NSCLC cells eventually become resistant to cisplatin because of the long-term use of it. 15 , 16 Novel approaches are required to overcome the resistance of cisplatin in NSCLC.…”

Non-small cell lung cancer in elderly – retrospective study comparing single-agent versus doublet chemotherapy

“…Patients treated with cisplatin were more predisposed to both haematologic and non--haematologic toxicity. 8 The Japanese trial JCOG0803/WJOG4307L also demonstrated that the combination ChT with cisplatin was not associated with superior overall survival. This trial compared tri -weekly docetaxel as monotherapy to a combination therapy (weekly cisplatin plus docetaxel) in stage III or IV NSCLC with ≥ 70 years with ECOG performance status 0 -1.…”

Treatment of metastatic non-small cell lung cancer: 2018 guidelines of the Italian Association of Medical Oncology (AIOM)

“…In patients with advanced NSCLC aged >70 years or with PS 2, single-agent chemotherapy with a third-generation agent remains the standard of care, while a platinumbased doublet chemotherapy (usually with carboplatin) is recommended only in selected cases (Table 4). [81][82][83][84][85][86][87][88][89]…”