Weekly paclitaxel combined with monthly carboplatin versus single-agent therapy in patients age 70 to 89: IFCT-0501 randomized phase III study in advanced non-small cell lung cancer (NSCLC).

Abstract

2 Background: Incidence of advanced NSCLC in the elderly is increasing. Specific trials for elderly are seldom and those patients are not optimally treated. Current recommendations are monotherapies with gemcitabine or vinorelbine. Methods: French multicentric randomized phase III study in pts aged 70 to 89, PS 0-2 with advanced NSCLC not irradiable, comparing a 3-weekly single agent therapy (gemcitabine 1,150 mg/m2 or vinorelbine 30 mg/m2, d1, d8: arm A) with carboplatin AUC 6 every 4 weeks + paclitaxel 90 mg/m2 (d1,8,15) doublet (arm B). Five cycles of single agent and 4 cycles of the doublet were to be given. Second-line in case of toxicity or progressive disease was fixed with erlotinib 150 mg/d. The main endpoint was overall survival. Results: 451 pts were included from 04/2005 to 12/2009 by 60 centers. Males were 73.8%, median age was 77.2 years (range 70-89). PS was 0-1 in 73.6%. The 2 arms were well-balanced for pts characteristics. At time of second planned intermediate analysis (after two-third of expected deaths, i.e. 224), 451 pts were randomized, out of the 522 initially planned. The steering committee advice was to stop the inclusions. Overall survival of the 313 pts analysed at this time was significantly longer in arm B (median: 10.4 months, 95%CI: [8.2; 15.0] vs. 6.2 months, 95%CI: [5.3; 7.5] for arm A, (HR = 0.60, 95%CI : [0.46; 0.78], p = 0.0001). Median PFS was 6.3 months, 95%CI: [5.5; 6.9] in arm B vs. 3.2 months, 95%CI: [0.44; 0.70] (HR = 0.55, 95%CI: [0.44; 0.70], p < 0.0001). Grade 3-4 haematological toxicities were significantly more frequent in arm B (17.9% vs. 54.1%). No significant difference was observed in early deaths (arm A: 23.7%, arm B: 16.6%). Survival, response and toxicity data for the whole series of 451 pts will be updated at time of the meeting. Conclusions: Paclitaxel and carboplatin doublet provides a significantly longer survival in elderly pts with advanced NSCLC than current standard single agent therapy, with acceptable toxicity, making it a new treatment paradigm for PS 0-2 pts ≥ 70 years. [Table: see text]

Geriatric Oncology: An Overview of Progresses and Challenges

“…In NSCLC, four randomized studies have explored the use of chemotherapy in the elderly (53)(54)(55)(56). The ELVIS trial demonstrated that single agent vinorelbine increased survival and quality of life over best supportive care (53).…”

Elderly Patients with Advanced Non-Small Cell Lung Cancer: What Treatment?

“…Response rate was 29% versus 10.9%, respectively. However, grade 3-4 hematologic toxicities and treatment-related deaths were significantly more frequent in patients treated with carboplatin and paclitaxel as compared to single-agent gemcitabine or vinorelbine [14]. Another phase III randomized trial enrolled 181 patients, aged > 70 years and with PS < 2, to receive two doublets, carboplatin (AUC 5 on day 1) plus gemcitabine (1250 mg/m on day 1 and 8) or paclitaxel (175 mg/m on day 1), every 3 weeks for a maximum of 4 cycles.…”

Update on nonsmall cell lung cancer

“…Finally, the first phase 3 randomised trial of platinum-based doublet therapy in an elderly population, presented in the plenary session of the 2010 ASCO meeting by the French Intergroup, addressed many issues raised by previous phase 2 trials [117]. This trial included 451 patients .70 yrs, and was closed at the second interim analysis since results greatly favoured weekly paclitaxel-monthly carboplatin doublet over the monotherapy arm (either vinorelbin or gemcitabine, depending on the choice of the centre).…”