Lung Adjuvant Cisplatin Evaluation (LACE): A pooled analysis of five randomized clinical trials including 4,584 patients

Abstract

7008 Background: Several recent trials have shown a benefit of adjuvant cisplatin-based chemotherapy on overall survival (OS) in patients with non-small cell lung cancer (NSCLC). The aim of the Lung Adjuvant Cisplatin Evaluation (LACE) is to identify treatment options associated with a higher benefit, or groups of patients benefiting more from adjuvant chemotherapy. Methods: Individual patient data were collected and pooled from the five largest trials (ALPI, ANITA, BLT, IALT and JBR10) of cisplatin-based chemotherapy in completely resected patients, conducted after the NSCLC-meta-analysis (BMJ 1995, update ongoing). The interactions between patient subgroups or treatment types and chemotherapy effect on OS were analysed using hazard ratios (HR) and logrank tests stratified by trial. Results: With a median follow-up of 5.1 years, the overall HR of death was 0.89 (95% confidence interval [CI]: 0.82–0.96; p<0.005) corresponding to a 5-year absolute benefit of 4.2% with chemotherapy. There was no heterogeneity of chemotherapy effect among trials. The benefit varied with stage (test for trend, p=0.046) with the HR for stage I-A 1.41 [95% CI: 0.96–2.09], stage I-B 0.93 [0.78–1.10], stage II 0.83 [0.73–0.95] and stage III 0.83 [0.73–0.95]. The effect of chemotherapy did not vary significantly (test for interaction, p=0.10) with the associated drugs: vinorelbine (HR=0.80 [0.70–0.91]) etoposide/vinca-alcaloide (0.93 [0.80–1.07]) or other (0.98 [0.84–1.14]). There was no interaction between chemotherapy and sex, age, planned radiotherapy or planned total dose of cisplatin. Conclusions: Adjuvant cisplatin-based chemotherapy improves survival in patients with NSCLC. This benefit depends on stage and is greatest in patients with stages II and III. Our analysis suggests that platinum-based adjuvant chemotherapy may not benefit stage I-A patients. Results of disease-free survival will be presented at the meeting. Supported by PHRC and LNLCC [Table: see text]

Pack‐years of cigarette smoking as a prognostic factor in patients with stage IIIB/IV nonsmall cell lung cancer

“…Patients with stage IV lung adenocarcinoma whose tumors harbor EGFR mutations in exon 19 or 21 are reported to have response rates >70% and prolonged progression‒free survival after treatment with the EGFR tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib (graded according to the American Joint Committee on Cancer staging system) 18‐22. The presence of EGFR mutations is reported to predict response to EGFR TKI therapy better than smoking status and may be a positive prognostic factor in patients with advanced lung adenocarcinoma irrespective of therapy 18, 23…”

Prognostic factors for survival of stage I nonsmall cell lung cancer patients

“…8 A meta-analysis of recent adjuvant, cisplatin-based chemotherapy trials also did not report any survival benefit from the use of chemotherapy for patients with stage I NSCLC. 9 The Cancer and Leukemia Group B (CALGB) 9633 study reported a 12% reduction in mortality at 4 years with adjuvant carboplatin plus paclitaxel in patients with stage IB NSCLC; however, after a longer follow-up, the improvement in survival no longer was significant. 10 Subgroup analysis showed that patients with stage IB NSCLC who had tumors that measured 4 cm did derive a survival benefit from the use of adjuvant chemotherapy.…”

Optimal Adjuvant Therapy for Non-Small Cell Lung Cancer—How to Handle Stage I Disease

“…In an attempt to understand the overall results of the large adjuvant trials that have occurred since the 1995 metaanalysis, an individual patient meta-analysis of the five largest, cisplatin-based studies was conducted (ALPI, BLT, IALT, JBR.10, and ANITA)-the Lung Adjuvant Cisplatin Evaluation (LACE). That study found a 5.3% absolute survival advantage at 5 years (HR, 0.89; 95% CI, 0.82-0.96; p ϭ .004) for adjuvant cisplatin therapy overall [10], thus reinforcing the need to adequately power adjuvant trials for this range of benefit. The stage IB subset analysis trended toward benefit (HR, 0.92), but failed to reach statistical significance (95% CI, 0.78 -1.10), while a detriment for chemotherapy was suggested in stage IA patients (HR, 1.41; 95% CI, 0.96 -2.09).…”