Outcomes for Elderly, Advanced-Stage Non–Small-Cell Lung Cancer Patients Treated With Bevacizumab in Combination With Carboplatin and Paclitaxel: Analysis of Eastern Cooperative Oncology Group Trial 4599

TLDR

Elderly patients with advanced non‑small‑cell lung cancer benefit from platinum‑based two‑drug chemotherapy, and adding bevacizumab to carboplatin and paclitaxel improves survival for advanced nonsquamous disease as shown in ECOG 4599. The study performed a subset analysis of ECOG 4599 to evaluate outcomes in patients aged 70 or older with advanced nonsquamous NSCLC. The analysis compared outcomes, patient characteristics, efficacy, and toxicity between carboplatin/paclitaxel (PC) and carboplatin/paclitaxel/bevacizumab (PCB) regimens in elderly patients, also contrasting them with younger patients. In elderly patients, PCB produced a non‑significant trend toward higher response rate and progression‑free survival but similar overall survival, while markedly increasing grade 3‑5 toxicities and adverse events, indicating no clear survival benefit and warranting prospective evaluation of its therapeutic index.

Abstract

Fit elderly patients with advanced non-small-cell lung cancer (NSCLC) benefit from platinum-based, two-drug chemotherapy. Bevacizumab (B) in combination with carboplatin (C) and paclitaxel (P) improves survival for advanced, nonsquamous NSCLC, as evidenced in Eastern Cooperative Oncology Group (ECOG) 4599. We conducted a subset analysis of ECOG 4599 to determine the outcome for elderly patients.ECOG 4599 randomly assigned patients with advanced nonsquamous NSCLC to PC or to PCB. We analyzed outcome in patients who were at least 70 years of age at the time of study entry. Patient characteristics, efficacy, and toxicity data were compared between PC and PCB for the elderly. Outcomes for elderly and younger patients (< 70 years) treated with PCB were also compared.Among elderly patients (n = 224; 26%), there was a trend towards higher response rate (29% v 17%; P = .067) and progression-free survival (5.9 v 4.9 months; P = .063) with PCB compared with PC, although overall survival (PCB = 11.3 months; PC = 12.1 months; P = .4) was similar. Grade 3 to 5 toxicities occurred in 87% of elderly patients with PCB versus 61% with PC (P < .001), with seven treatment-related deaths in the PCB arm compared with two with PC. Elderly patients had higher incidence of grade 3 to 5 neutropenia, bleeding, and proteinuria with PCB compared with younger patients.In elderly NSCLC patients, PCB was associated with a higher degree of toxicity, but no obvious improvement in survival compared with PC. Data from this unplanned, retrospective analysis justify prospective evaluation of the therapeutic index of PCB regimen in elderly patients.