Meta-Analysis Shows Survival Benefit of Preoperative Chemotherapy in NSCLC

Key Points

  • Preoperative chemotherapy was associated with a 13% improvement in overall survival.
  • Preoperative chemotherapy was associated with a 15% improvement in recurrence-free survival and a 31% improvement in time to distant recurrence.

In a systematic review and individual patient meta-analysis reported in The Lancet, the NSCLC Meta-analysis Collaborative Group found that neoadjuvant therapy for non–small cell lung cancer (NSCLC) was associated with a significant 13% reduction in risk of death. Significant benefits in recurrence-free survival and time to distant recurrence were also observed.

Study Details

The study involved a systematic search for trials of preoperative chemotherapy in resectable NSCLC that began after January 1965. Updated individual participant data were centrally collected and analyzed. Results from individual randomized controlled trials (both published and unpublished) were combined using a two-stage fixed-effect model. The primary outcome measure was overall survival.

The search yielded 19 eligible trials, including 17 published and 2 unpublished trials. Data could not be supplied for three trials, and one trial recruited only two patients. The analysis thus included 15 eligible randomized controlled trials involving a total of 2,385 patients, which represented 92% of all randomized patients in the eligible trials.

For patients receiving chemotherapy plus surgery vs those receiving surgery alone with available data, 42% vs 38% were aged < 60 years and 19% vs 20% were aged ≥ 70 years, 79% vs 81% were male; 28% vs 29% had adenocarcinoma and 49% vs 52% had squamous histology; disease stage was IB in 43% vs 46%, IIB in 24% vs 26%, and IIIA in 24% and 21%; and performance status was 0 in 43% vs 43% and 1 in 45% vs 46%. 

Improved Overall Survival

The meta-analysis showed a significant improvement in overall survival with neoadjuvant therapy (hazard ratio [HR] = 0.87, P = .007), with no evidence of a difference in risk among trials (P = .18 for heterogeneity, I² = 25%). The finding represents a 5-year overall survival advantage of 45% vs 40%.

There was no clear evidence that the effect of preoperative chemotherapy differed according to whether chemotherapy was given preoperatively or both preoperatively and postoperatively (P = .23 for interaction) or the number of preoperative chemotherapy cycles (P = .68 for interaction). For all trials and in analysis including only trials using platinum-based regimens, there was no evidence that the effect of chemotherapy differed according to type of chemotherapy regimen (P = .94 for interaction in full analysis, P = .91 for interaction in platinum-based therapy analysis), number of chemotherapy agents per regimen (P = .84 and P = .60 for interaction), or both type of chemotherapy regimen and number of agents (P = .79 and P = .62 for interaction).

No difference in effect was observed according to whether cisplatin- or carboplatin-based regimens were used (P = .48 for interaction) or whether patients received postoperative radiotherapy (P = .87 for interaction). There was also no clear evidence of difference in effect according to age (P = .83 for interaction), sex (P = .62 for interaction), performance status (P = .14 for interaction), histology (P = .16 for interaction), or clinical stage (P = .64 for interaction).  

Improved Recurrence-Free Survival, Time to Distant Recurrence

Both recurrence-free survival (HR = 0.85,  P = .002; P = .41 for heterogeneity) and time to distant recurrence (HR = 0.69, P < .0001; P = .40 for heterogeneity) were significantly improved with preoperative chemotherapy, and a nonsignificant improvement in time to locoregional recurrence was observed (HR = .88, P = .20; P = .89 for heterogeneity). The data represent an improvement in 5-year recurrence-free survival of 36% vs 30%.  

The investigators concluded, “Findings, which are based on 92% of all patients who were randomised, and mainly stage IB–IIIA, show preoperative chemotherapy significantly improves overall survival, time to distant recurrence, and recurrence-free survival in resectable NSCLC. The findings suggest this is a valid treatment option for most of these patients. Toxic effects could not be assessed.”

Sarah Burdett, of the MRC Clinical Trials Unit at University College London, is the corresponding author for the Lancet article.

The study was funded by the Medical Research Council UK. For full disclosures of the study authors, visit

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