Several recent trials have shown a significant overall survival (OS) benefit from postoperative cisplatin-based chemotherapy in patients with non-small-cell lung cancer (NSCLC). The aim of the Lung ...Adjuvant Cisplatin Evaluation was to identify treatment options associated with a higher benefit or groups of patients who particularly benefit from postoperative chemotherapy.
Individual patient data were collected and pooled from the five largest trials (4,584 patients) of cisplatin-based chemotherapy in completely resected patients that were conducted after the 1995 NSCLC meta-analysis. The interactions between patient subgroups or treatment types and chemotherapy effect on OS were analyzed using hazard ratios (HRs) and log-rank tests stratified by trial.
With a median follow-up time of 5.2 years, the overall HR of death was 0.89 (95% CI, 0.82 to 0.96; P = .005), corresponding to a 5-year absolute benefit of 5.4% from chemotherapy. There was no heterogeneity of chemotherapy effect among trials. The benefit varied with stage (test for trend, P = .04; HR for stage IA = 1.40; 95% CI, 0.95 to 2.06; HR for stage IB = 0.93; 95% CI, 0.78 to 1.10; HR for stage II = 0.83; 95% CI, 0.73 to 0.95; and HR for stage III = 0.83; 95% CI, 0.72 to 0.94). The effect of chemotherapy did not vary significantly (test for interaction, P = .11) with the associated drugs, including vinorelbine (HR = 0.80; 95% CI, 0.70 to 0.91), etoposide or vinca alkaloid (HR = 0.92; 95% CI, 0.80 to 1.07), or other (HR = 0.97; 95% CI, 0.84 to 1.13). Chemotherapy effect was higher in patients with better performance status. There was no interaction between chemotherapy effect and sex, age, histology, type of surgery, planned radiotherapy, or planned total dose of cisplatin.
Postoperative cisplatin-based chemotherapy significantly improves survival in patients with NSCLC.
To evaluate the impact of adjuvant cisplatin-vinorelbine in completely resected non-small cell lung cancer and identify patients likely to benefit from this regimen in the Lung Adjuvant Cisplatin ...Evaluation (LACE) database. The overall LACE meta-analysis showed survival benefit with cisplatin-based adjuvant chemotherapy (5-year survival benefit of 5.4%, hazard ratio HR 0.89, p = 0.004). Subgroup analysis for the cisplatin-vinorelbine regimen was prespecified in the LACE statistical analysis plan. Patients randomized to cisplatin-vinorelbine or observation were the largest subgroup (41%) and the most homogeneous in terms of drug doses and eligibility.
The LACE-vinorelbine cohort included trials evaluating cisplatin-vinorelbine versus observation. Overall survival was the primary end point. Other studies randomizing patients to other chemotherapy or observation (LACE-other) were also evaluated.
The LACE-vinorelbine cohort included 1888 patients from four studies (Adjuvant Navelbine International Trialist Association, Big Lung Trial, International Adjuvant Lung Cancer Trial, and National Cancer Institute of Canada Clinical Trials Group JBR.10). Baseline characteristics were similar to the LACE-other but had fewer patients with stage IA (2% versus 11%). Survival improvement at 5 years was 8.9% with cisplatin-vinorelbine versus observation (HR 0.80, 95% confidence interval: 0.70–0.91, p <0.001). Stage was a significant predictor for survival (test for trend, p = 0.02; benefit at 5 years: 14.7% stage III, 11.6% stage II, and 1.8% stage I). Similar benefits were seen for disease-free survival (HR 0.75 0.67–0.85, p <0.001, stage III HR 0.62, 0.50–0.76, stage II HR 0.69, 0.57–0.83, and stage I HR 0.95, 0.767ndash;1.19). The overall result was statistically superior to LACE-other (LACE other HR 0.95, 0.86–1.05, interaction p = 0.04).
In subgroup analyses, adjuvant cisplatin-vinorelbine provides a superior survival benefit and can be recommended in completely resected stages II and III non-small cell lung cancer.
This pooled analysis was undertaken to assess the efficacy and toxicity of adjuvant cisplatin-based chemotherapy in elderly patients with non-small-cell lung cancer (NSCLC).
We used individual ...patient data from 4,584 patients enrolled onto five trials of cisplatin-based chemotherapy who form the basis for the Lung Adjuvant Cisplatin Analysis (LACE) pooled analysis. Patient and treatment characteristics, overall and event-free survival, cause-specific mortality, chemotherapy toxicity and delivery were compared among three age groups: 3,269 young (71%; < 65), 901 midcategory (20%; 65 to 69), and 414 elderly patients (9%; >or= 70). Log-rank tests stratified by trials were used with a test for trend to study the effect of chemotherapy on survival according to age.
The hazard ratio (HR) of death for the young patients was 0.86 (95% CI, 0.78 to 0.94), 1.01 for the midcategory (95% CI, 0.85 to 1.21), and 0.90 for elderly patients (95% CI, 0.70 to 1.16; test for trend: P = .29). The HR for event-free survival was 0.82 for young (95% CI, 0.75 to 0.90), 0.90 for the midcategory (95% CI, 0.76 to 1.06), and 0.87 for elderly patients (95% CI, 0.68 to 1.11; test for trend: P = .42). More elderly patients died from non-lung cancer-related causes (12% young, 19% midcategory, 22% elderly; P < .0001). No differences in severe toxicity rates were observed. Elderly patients received significantly lower first and total cisplatin doses, and fewer chemotherapy cycles (chi(2) P < .0001).
Adjuvant cisplatin-based chemotherapy should not be withheld from elderly patients with NSCLC purely on the basis of age.
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