Thursday, December 31, 2009

Adjuvant Chemotherapy for NSCLC, updates on two influential trials

JCO this week: Two of the more influencial trials on adjuvant chemotherapy for resected NSCLC are updated, the JBR-10 and the IALT studies. The JBR-10 study continues to show a survival benefit out to almost 10 years, though the stage IBs seemed not to benefit. The IALT study continued to demonstrate a DFS benefit, but the OS figures had slipped to non-significance.

Links and abstracts:

Randomized Phase III Trial of Vinorelbine Plus Cisplatin Compared With Observation in Completely Resected Stage IB and II Non-Small-Cell Lung Cancer: Updated Survival Analysis of JBR-10 [Thoracic Oncology]: "Purpose

Adjuvant cisplatin-based chemotherapy (ACT) is now an accepted standard for completely resected stage II and III A non–small-cell lung cancer (NSCLC). Long-term follow-up is important to document persistent benefit and late toxicity. We report here updated overall survival (OS) and disease-specific survival (DSS) data.

Patients and Methods

Patients with completely resected stage IB (T2N0, n = 219) or II (T1-2N1, n = 263) NSCLC were randomly assigned to receive 4 cycles of vinorelbine/cisplatin or observation. All efficacy analyses were performed on an intention-to-treat basis.


Median follow-up was 9.3 years (range, 5.8 to 13.8; 33 lost to follow-up); there were 271 deaths in 482 randomly assigned patients. ACT continues to show a benefit (hazard ratio [HR], 0.78; 95% CI, 0.61 to 0.99; P = .04). There was a trend for interaction with disease stage (P = .09; HR for stage II, 0.68; 95% CI, 0.5 to 0.92; P = .01; stage IB, HR, 1.03; 95% CI, 0.7 to 1.52; P = .87). ACT resulted in significantly prolonged DSS (HR, 0.73; 95% CI, 0.55 to 0.97; P = .03). Observation was associated with significantly higher risk of death from lung cancer (P = .02), with no difference in rates of death from other causes or second primary malignancies between the arms.


Prolonged follow-up of patients from the JBR.10 trial continues to show a benefit in survival for adjuvant chemotherapy. This benefit appears to be confined to N1 patients. There was no increase in death from other causes in the chemotherapy arm."

Long-Term Results of the International Adjuvant Lung Cancer Trial Evaluating Adjuvant Cisplatin-Based Chemotherapy in Resected Lung Cancer [Thoracic Oncology]


Based on 5-year or shorter-term follow-up data in recent randomized trials, adjuvant cisplatin-based chemotherapy is now generally recommended after complete surgical resection for patients with non–small-cell lung cancer (NSCLC). We evaluated the results of the International Adjuvant Lung Cancer Trial study with three additional years of follow-up.

Patients and Methods

Patients with completely resected NSCLC were randomly assigned to three or four cycles of cisplatin-based chemotherapy or to observation. Cox models were used to evaluate treatment effect according to follow-up duration.


The trial included 1,867 patients with a median follow-up of 7.5 years. Results showed a beneficial effect of adjuvant chemotherapy on overall survival (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.02; P = .10) and on disease-free survival (HR, 0.88; 95% CI, 0.78 to 0.98; P = .02). However, there was a significant difference between the results of overall survival before and after 5 years of follow-up (HR, 0.86; 95% CI, 0.76 to 0.97; P = .01 v HR, 1.45; 95% CI, 1.02 to 2.07; P = .04) with P = .006 for interaction. Similar results were observed for disease-free survival. The analysis of non-lung cancer deaths for the whole period showed an HR of 1.34 (95% CI, 0.99 to 1.81; P = .06).


These results confirm the significant efficacy of adjuvant chemotherapy at 5 years. The difference in results beyond 5 years of follow-up underscores the need for the long-term follow-up of other adjuvant lung cancer trials and for a better identification of patients deriving long-term benefit from adjuvant chemotherapy.

No comments: