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
Last Modified: June 2, 2003
Presenter: T. LeChevalier
Presenter's Affiliation: Institut Gustave Roussy
Type of Session: Plenary
- 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.
- 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.
- 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.
- 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.
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