Preoperative Chemotherapy in Patients With Resectable Non-Small Cell Lung Cancer: Results of the MRC LU22/NVALT 2/EORTC 08012 Multicentre Randomised Trial and Update of Systematic Review

Lancet. 2007 Jun 9;369(9577):1929-37. doi: 10.1016/S0140-6736(07)60714-4.

Abstract

Background: Although surgery offers the best chance of cure for patients with non-small cell lung cancer (NSCLC), the overall 5-year survival rate is modest, and improvements are urgently needed. In the 1990s, much interest was generated from two small trials that reported striking results with neo-adjuvant chemotherapy, and therefore our intergroup randomised trial was designed to investigate whether, in patients with operable non-small cell lung cancer of any stage, outcomes could be improved by giving platinum-based chemotherapy before surgery.

Methods: Patients were randomised to receive either surgery alone (S), or three cycles of platinum-based chemotherapy followed by surgery (CT-S). Before randomisation, clinicians chose the chemotherapy that would be given from a list of six standard regimens. The primary outcome measure was overall survival, which was analysed on an intention-to-treat basis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN25582437.

Results: 519 patients were randomised (S: 261, CT-S: 258) from 70 centres in the UK, Netherlands, Germany, and Belgium. Most (61%) were clinical stage I, with 31% stage II, and 7% stage III. Neo-adjuvant chemotherapy was feasible (75% of patients received all three cycles of chemotherapy), resulted in a good response rate (49% [95% CI 43%-55%]) and down-staging in 31% (25%-37%) of patients, and did not alter the type or completeness of the surgery (lobectomy: S: 56%, CT-S: 60%, complete resection: S: 80%, CT-S: 82%). Post-operative 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). Updating the systematic review by addition of the present result suggests a 12% relative survival benefit with the addition of neoadjuvant chemotherapy (1507 patients, HR 0.88, 95% CI 0.76-1.01, p=0.07), equivalent to an absolute improvement in survival of 5% at 5 years

Interpretation: Although there was no evidence of a difference in overall survival with neo-adjuvant chemotherapy, the result is statistically consistent with previous trials, and therefore adds considerable weight to the current evidence.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Preoperative Care / methods*
  • Quality of Life
  • Surveys and Questionnaires
  • Survival Analysis

Associated data

  • ISRCTN/ISRCTN25582437