Older persons with advanced non-small cell lung cancer (NSCLC) can gain 4 months in overall survival (OS) when treated with a paclitaxel/carboplatin doublet, vs a single agent, according to French investigators who reported highly significant improvements at the Plenary Session of the 2010 ASCO Annual Meeting.¹

The phase III study was devoted to determining safety and efficacy of relatively aggressive treatment in patients aged 70 to 89. Based on the findings, weekly paclitaxel and monthly carboplatin represents a new treatment paradigm for the elderly, said principal investigator Elisabeth Quoix, MD, Professor of Medicine at University Hospital, Strasbourg, on behalf of The French Intergroup of Thoracic Oncology.

"These results demonstrate that a more intensive regimen typically reserved for younger patients can be effective and tolerable in this group as well," she said.

Impact in Europe vs United States

ASCO guidelines state that first-line chemotherapy should not be selected based exclusively on the patient's age,² but those of the European Organisation for Research and Treatment of Cancer (EORTC) are more conservative, stating that third-generation single-agent treatment is the standard of care for elderly patients.³

Corey Langer, MD, who has led many NSCLC treatment trials in the elderly, called the study one of the most important to be presented at ASCO. "It was a well constructed trial showing a whopping survival benefit," he told The ASCO Post. He said the findings will be particularly relevant in Europe, where doublets are not commonly used in the elderly, but informs U.S. practice as well, since aggressive treatment is often reserved for the fittest patients. Dr. Langer is Director of Thoracic Oncology at Abramson Cancer Center at the University of Pennsylvania, Philadelphia.

Trial Rationale

The Intergroupe Francophone de Cancérologie Thoracique (IFCT)-0501 study enrolled 451 patients aged 70 to 89 from 62 French centers. The investigators aimed to compare single-agent treatment to a platinum-based doublet specifically in elderly patients; no previous study dedicated to this group has been performed. The only indication in favor of a platin-based doublet was a subset analysis in a phase III trial conducted by Lilenbaum and colleagues, in which carboplatin/paclitaxel was more efficacious than the taxane alone.⁴

In the current study, patients' median age was 77, most had stage IV adenocarcinoma but good performance status, and approximately 20% had never smoked. They were randomly assigned to single-agent therapy with either gemcitabine (Gemzar) at 1,150 mg/m² or vinorelbine at 30 mg/m² days 1 and 8 every 3 weeks for five cycles, or to combination therapy with carboplatin (area under the curve [AUC] 6) every 4 weeks plus weekly paclitaxel at 90 mg/m² (days 1, 8, and 15) for four cycles. Upon disease progression, all patients could receive erlotinib (Tarceva) at 150 mg/d. The median number of chemotherapy cycles was four for both arms.

Doublet Adds 4 Months to Survival

The study was stopped early when an interim analysis found that OS and progression-free survival (PFS) were longer in the combination arm. Median follow-up was 21.3 months as of the data cutoff in March 2010.

Overall survival was significantly improved for patients receiving the paclitaxel/carboplatin doublet: 10.3 vs 6.2 months with the single agent (P = .00004). One-year PFS rates were 45.1% and 26.9%, respectively (see Figure 1 on page 2).

An OS benefit was observed for most subgroups, including patients older than 80 years, smokers, and those with poor performance status, lower activities of daily living scores, and greater weight loss.

Similarly, median PFS was improved from 3.0 months with the single agent to 6.1 months with the doublet (P < .000001). One-year progression-free survival was 2.3% vs 15.4%, respectively.

Objective responses were observed in 10.9% of the single-agent arm vs 29% of the doublet arm (P < .00001). Progressive disease was observed in 21.8% of patients on single agents but only 7.1% of those on the doublet (P < .0001).

Hematologic toxicity was significantly greater with the doublet regimen, but neuropathy grade 3 or 4 was limited to < 3% of patients in this arm. There were more toxic deaths (6.6% vs 1.8%) with the doublet arm. However, early deaths (within 3 months) were more common with the single agents (25.6% vs 16.7%). ■

References

1. Quoix EA, Oster J, Westeel V, et al: 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. 2010 ASCO Annual Meeting. Abstract 2. Presented June 6, 2010.

2. Azzoli CG, Baker S, Temin S, et al: American Society of Clinical Oncology Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 27:6251-6256, 2009.

3. Pallis AG, Gridelli C, van Meerbeeck JP, et al: EORTC Elderly Task Force and Lung Cancer Group and International Society for Geriatric Oncology experts' opinion for the treatment of non-small-cell lung cancer in an elderly population. Ann Oncol 21:692-706, 2010.

4. Lilenbaum RC, Herndon JE, List MA, et al: Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: The Cancer and Leukemia Group B (study 9730). J Clin Oncol 23:190-196, 2005.