Results of a randomized International Adjuvant Lung Cancer Trial (IALT): cisplatin-based chemotherapy (CT) vs no CT in 1867 patients (pts) with resected non-small cell lung cancer (NSCLC)

Reviewer: Walter Sall, MD
OncoLink
Last Modified: June 2, 2003

Presenter: T. LeChevalier
Presenter's Affiliation: Institut Gustave Roussy
Type of Session: Plenary

Background

1.2 million cases of NSCLC are diagnosed yearly worldwide. 30% of these are resectable but local therapy is not consistently curative. Distant metastases are common.
The 1995 MRC lung cancer trial suggested a 5% 5 year OS benefit, but patient numbers were too low to reach statistical significance.
This prompted the IALT to conduct a large randomized trial powered to detect benefit of post-operative CT.

Materials and Methods

Prospective randomized international study which accrued 1897 patients from 1995-2000.
Eligible patients had completely resected Stage I-III NSCLC. Chemo must start within 60 days of surgery.
Each center set their own policy regarding chemotherapy and radiation (RT; doses up to 60 Gy). Chemotherapy had to be cisplatin based. The target cumulative cisplatin dose was 300-400 mg/m2.
Primary end point was OS. Secondary end points included DFS, secondary malignancy and toxicity.

Results

The two arms were well balanced with regard to prognostic factors and patient characteristics. 80% of patients were male; 2/3 underwent lobectomy, 1/3 pneumonectomy. 36% were stage I, 25% stage II and 39% stage III.
With a median follow up of 56 months, 5 year OS was 44.5% with CT and 40.4% without (p=0.03). 5 year DFS was 39.4% with CT and 34.3% without (p<0.003).
CT toxicity included a 0.8% risk of treatment related death and a 23% risk of grade IV toxicity, primarily neutropenia.

Author's Conclusions

This trial shows a statistically significant OS and DFS benefit to post-operative cisplatin based chemotherapy for completely resected NSCLC.
No subgroup was found to benefit more than others.
The rather high toxicity of this chemotherapy regimen indicates that new agents with better activity and toxicity profiles warrant further investigation.

Clinical/Scientific Implications

Adjuvant chemotherapy in the setting of completely resected NSCLC has long been the subject of controversy. This large, well designed trial indicates the existence of a small but statistically significant survival benefit to such chemotherapy. However, the toxicity is high and calls into question whether such a small clinical benefit warrants the risk. In addition, this trial contradicts several admittedly smaller recent trials which show no benefit to post-operative CT. Further study is clearly warranted. Perhaps the pooled analysis planned by the IALT will shed more light on this controversial issue.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.