An early online publication in the Lancet reports the results of the LU22 trial of preoperative chemotherapy in patients with resectable nonsmall-cell lung cancer (NSCLC).
The authors note that although surgery offers the best chance of cure for patients with NSCLC, the overall five-year survival rate is modest. Their study investigated whether outcomes could be improved in patients with operable NSCLC at any stage, by giving platinum-based chemotherapy before surgery.
The study involved 519 patients, most (61%) of whom were clinical stage I, with 31% stage II and 7% stage III. They were randomised to receive either surgery alone (S, n=261), or three cycles of platinum-based chemotherapy followed by surgery (CT-S, n= 258). Before randomisation, clinicians chose the chemotherapy that would be given from a list of six standard regimens. The primary outcome was overall survival on an intention-to-treat basis.
A total of 75% of patients received all three cycles of chemotherapy, which resulted in a good response rate (49% [95% CI 43%–55%]), downstaging in 31% (25–37%), and no change to the type or completeness of the surgery. Postoperative complications were not increased in the CT-S group, and no impairment of quality of life was observed. However, there was no evidence of a benefit in terms of overall survival (hazard ratio [HR] 1.02, 95% CI 0.80–1.31, p=0.86).
These data were added to an existing systematic review which suggested a 12% relative survival benefit with the addition of neoadjuvant chemotherapy (1,507 patients, HR 0.88, 95% CI 0.76–1.01, p=0.07), equivalent to an absolute improvement in survival of 5% at five years.
The researchers conclude: “Although there was no evidence of a difference in overall survival with neoadjuvant chemotherapy, the result is statistically consistent with previous trials, and therefore adds considerable weight to the current evidence.”
An accompanying commentary notes that these results were unexpected, given that more than 80% of patients received modern regimens (taxanes, vinorelbine, or gemcitabine) and compliance was high. It adds that the recruitment of a high percentage of patients with stage I disease, and early closure, led to an inconclusive result.
However a similar North American study evaluating preoperative paclitaxel/carboplatin was also negative (0.88, 0.63–1.23). Although the systematic review indicates a potential benefit from preoperative chemotherapy, the authors believe that the body of evidence to date favours postoperative chemotherapy.
They conclude: “Surgery, the most important component of combined modality treatment for early-stage NSCLC, should not be delayed, and systemic treatments should be administered postoperatively.”
Lancet early online publication, 4 June 2007