Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data

Abstract

SummaryBackgroundIndividual participant data meta-analyses of postoperative chemotherapy have shown improved survival for patients with non-small-cell lung cancer (NSCLC). We aimed to do a systematic review and individual participant data meta-analysis to establish the effect of preoperative chemotherapy for patients with resectable NSCLC.MethodsWe systematically searched for trials that started after January, 1965. Updated individual participant data were centrally collected, checked, and analysed. Results from individual randomised controlled trials (both published and unpublished) were combined using a two-stage fixed-effect model. Our primary outcome, overall survival, was defined as the time from randomisation until death (any cause), with living patients censored on the date of last follow-up. Secondary outcomes were recurrence-free survival, time to locoregional and distant recurrence, cause-specific survival, complete and overall resection rates, and postoperative mortality. Prespecified analyses explored any variation in effect by trial and patient characteristics. All analyses were by intention to treat.FindingsAnalyses of 15 randomised controlled trials (2385 patients) showed a significant benefit of preoperative chemotherapy on survival (hazard ratio [HR] 0·87, 95% CI 0·78–0·96, p=0·007), a 13% reduction in the relative risk of death (no evidence of a difference between trials; p=0·18, I2=25%). This finding represents an absolute survival improvement of 5% at 5 years, from 40% to 45%. There was no clear evidence of a difference in the effect on survival by chemotherapy regimen or scheduling, number of drugs, platinum agent used, or whether postoperative radiotherapy was given. There was no clear evidence that particular types of patient defined by age, sex, performance status, histology, or clinical stage benefited more or less from preoperative chemotherapy. Recurrence-free survival (HR 0·85, 95% CI 0·76–0·94, p=0·002) and time to distant recurrence (0·69, 0·58–0·82, p<0·0001) results were both significantly in favour of preoperative chemotherapy although most patients included were stage IB–IIIA. Results for time to locoregional recurrence (0·88, 0·73–1·07, p=0·20), although in favour of preoperative chemotherapy, were not statistically significant.InterpretationFindings, 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.FundingMedical Research Council UK.

Adaptive Neoadjuvant Chemotherapy Guided by 18 F-FDG PET in Resectable Non–Small Cell Lung Cancers: The NEOSCAN Trial

“…This accounts for a 5% absolute increase in survival over surgery alone. 3 Second, a neoadjuvant approach provides a discovery platform for in vivo assessment of tumor response. Third, tissue available pre- and post treatment allows for translational studies and the utilization of surrogate endpoints.…”

Trimodal therapy for stage III-N2 non-small-cell lung carcinoma: a single center retrospective analysis

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Neoadjuvant Oncogene-Targeted Therapy in Early Stage Non–Small-Cell Lung Cancer as a Strategy to Improve Clinical Outcome and Identify Early Mechanisms of Resistance

“…A meta-analysis of 15 trials (2385 patients) demonstrated significant but modest improvements in overall survival at 5 years from 40 to 45% (HR 0.87, 95% CI 0.78–0.96, P=0.007), time to distant recurrence at 5 years improved from 60% to 70% (HR 0.69, 95% CI 0.58–0.82; p<0.001) and a recurrence free survival improvement from 30% to 36% at 5 years across all stages (HR 0.85, 95% CI 0.76–0.94, P=0.002). 7 In addition to providing benefit to patients by potentially improving overall survival and reducing the risk of disease recurrence, evaluation of the tumor response to targeted therapy in the neoadjuvant setting provides an excellent opportunity to study residual disease, given that patients undergo definitive surgical resection as a predetermined part of their treatment plan. Tissue-based molecular evaluations of targeted therapy response in neoadjuvant treatment of early stage NSCLC have not been performed.…”