Lung Adjuvant Cisplatin Evaluation (LACE) Study Results

[CaroleHammett]

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August 19, 2008

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Use of Cisplatin-Based Chemotherapy in NSCLC

Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group

J Clin Oncol. 2008 Jul 20;26(21):3552-3559, JP Pignon, H Tribodet, GV Scagliotti, JY Douillard, FA Shepherd, RJ Stephens, A Dunant, V Torri, R Rosell, L Seymour, SG Spiro, E Rolland, R Fossati, D Aubert, K Ding, D Waller, T Le Chevalier, LACE Collaborative Group

Evidence regarding the benefit of postoperative adjuvant chemotherapy in patients with non–small cell lung cancer (NSCLC) is conflicting. While some studies show improved overall survival (OS), others do not. Therefore, the Lung Adjuvant Cisplatin Evaluation (LACE) study was undertaken to identify the most beneficial therapeutic approaches in these patients and to determine whether subsets of patients may receive improved benefit from adjuvant chemotherapy.

The LACE study was a pooled analysis of data from 5 randomized controlled trials, each enrolling >300 patients with resectable NSCLC. All of the studies included patients who received cisplatin-containing regimens. Variables examined included baseline patient and tumor characteristics, treatment toxicity, and outcomes. The primary end point was OS. Secondary end points were disease-free survival (DFS), number of deaths attributable and not attributable to lung cancer, OS and DFS as related to type of treatment, and toxicity.

The study analyses were based on data from 4584 patients. Median follow-up duration was 5.2 years (range per trial, 4.7-5.9 years).

Chemotherapy vs no chemotherapy resulted in a significant benefit to patients in terms of OS (hazard ratio

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= 0.89; 95% confidence interval [CI], 0.82-0.96; P = .005); chemotherapy reduced the risk of death by 11%, with absolute benefits of 3.9% and 5.4% at 3 and 5 years, respectively. DFS was also greater with chemotherapy (HR = 0.84; 95% CI, 0.78-0.91; P < .001), with absolute benefits of 5.8% at both 3 and 5 years. No heterogeneity of these results was noted among the trials (P = .37).

Data were collected only for the maximum levels of toxicity, and not all trials reported all levels. Toxicity rates varied greatly among the trials. The overall rates of grade 3 and 4 toxicity were 66% and 32%, respectively. Neutropenia was the most commonly reported toxicity (9% and 28% for grades 3 and 4, respectively). Chemotherapy-related deaths occurred in 19 patients (0.9%).

The number of deaths attributable to lung cancer was lower in the chemotherapy group than in the no-chemotherapy group (5-year absolute benefit, 6.9%; HR = 0.83; 95% CI, 0.76-0.90; P <001> .02 for OS and DFS, respectively). However, the total dose of cisplatin was significantly higher in patients treated with vinorelbine (ie, >300 mg/m2 in 86% of patients vs 54% of those treated with other cisplatin doublets and 0% of those treated with a cisplatin triplet). This may have skewed interpretation of the results; therefore, they should be regarded with caution. In the cisplatin-treated patients, both tumor stage (IA) and performance status (PS = 2) were associated with significantly longer OS and DFS (for tumor stage, P = 0.4 for both OS and DFS; for performance status, P = .009 for OS and P = .01 for DFS).

The results indicate that cisplatin-based chemotherapy prolongs OS and DFS in patients with fully resected NSCLC. However, neither an optimal therapeutic approach nor factors predicting improved benefit emerged from this analysis, except for tumor stage and performance status. Future investigations should explore whether combining cisplatin with specific chemotherapeutic agents provides improved outcomes and whether combining radiotherapy with chemotherapy is beneficial.

This summary was written by the OncologySTAT editorial team.

Elsevier Copyright © 2008