Chemotherapy and surgery versus surgery alone in non-small cell lung cancer

 

Abstract

Background

The role of pre-operative chemotherapy in the treatment of patients with non-small cell lung cancer (NSCLC) was not clear. A systematic review and quantitative meta-analysis were therefore undertaken to evaluate the available evidence from randomised trials.

Objectives

To evaluate the effect of pre-operative chemotherapy on survival in patients with non-small cell lung cancer. If adequate data are available, to investigate whether or not pre-defined patient subgroups benefit more or less from pre-operative chemotherapy.

Search methods

MEDLINE and CANCERLIT searches for randomised controlled trials (RCTs) were supplemented by information from trial registers and by handsearching relevant meeting proceedings and by discussion with relevant trialists and organisations.

Selection criteria

RCTs were eligible for inclusion provided the patients had been randomised between chemotherapy followed by surgery versus surgery alone and that the method of randomisation precluded prior knowledge of the treatment to be assigned.

Data collection and analysis

A systematic review and meta-analysis based on aggregate data extracted from trial publications was carried out to assess the effectiveness of pre-operative chemotherapy in NSCLC. This involved identifying eligible RCTs and extracting aggregate data from the abstracts or reports of these RCTs. Hazard ratios were calculated from published summary statistics and then combined to give pooled estimates of treatment efficacy.

Main results

Twelve eligible RCTs were identified. Data were available from seven RCTs including 988 patients (75% of eligible patients). Pre-operative chemotherapy increased survival with a hazard ratio of 0.82 (95%CI 0.69-0.97) P = 0.022. This is equivalent to an absolute benefit of 6%, increasing overall survival across all stages of disease from 14% to 20% at 5 years. There was no evidence of statistical heterogeneity (P = 0.980, I² = 0).

Authors' conclusions

This analysis shows a significant increase in survival attributable to pre-operative chemotherapy. This is currently the best estimate of the effectiveness of this therapy, but is based on a small number of trials and patients. This analysis was unable to address important questions such as whether particular types of patients may benefit more or less from pre-operative chemotherapy or whether the early stopping of a number of included RCTs impacted on the results. These issues may be addressed by an ongoing individual patient data (IPD) meta-analysis.

 

Plain language summary

The pre-operative chemotherapy might increase survival in patients with non-small cell lung cancer when compared to surgery alone

The results of this systematic review suggest that pre-operative chemotherapy might increase survival in patients with non-small cell lung cancer when compared to surgery alone. However, an individual patient data systematic review and meta-analysis is needed to give us a more reliable assessment of the size of benefits and to explore whether pre-operative chemotherapy may be more or less effective for particular types of patients.

 

摘要

背景

非小細胞肺癌病人使用化學治療合併手術治療與單獨手術治療之比較

手術前化學治療在治療非小細胞肺癌的角色未明，故使用系統性的回顧和定量的統合分析來評估從隨機試驗所得到的證據

目標

評估手術前化學治療在非小細胞肺癌病人存活的效力。如果有足夠的數據，再探討預先定義的病人群是否從手術前化學治療受益更多或更少。

搜尋策略

以MEDLINE和CANCERLIT搜尋隨機對照試驗的資料，並輔以臨床試驗登錄和人工搜尋有關會議記錄和與有關人士及組織的討論。

選擇標準

隨機對照試驗須符合病人接受隨機分配至化學治療接著手術治療和只接受手術治療。隨機分配的方法是排除已知被分配的治療。

資料收集與分析

根據已發表的試驗所擷取的總計資料作系統性的回顧和統合分析，藉以評估非小細胞肺癌手術前化學治療的效益。這牽涉到確認符合資格的隨機對照試驗和從隨機對照試驗的摘要和報告擷取的總計資料。從已發表的概要統計然後加上匯集估計治療效果，來計算危險率(Hazard ratios)。

主要結論

確認了12個符合資格的隨機對照試驗。其中可得到資料的隨機對照試驗共7個，包含了988個病人（佔符合資格病人的75%）。手術前化學治療增加了存活，危險率是0.82 (95%CI 0.69–0.97) P值是 0.022。這相當於6%的絕對益處，疾病所有期別的5年整體存活，從14%增加到20%。沒有統計異質性的證據(P = 0.980, I2 = 0)。

作者結論

這個分析顯示手術前化學治療有顯著意義的增加存活。這是目前治療效益的最佳評估，但這分析是根據少數的試驗和病人數所得到的結果。這個分析無法回答重要的問題如是否有特定類型的病人可能從手術前化學治療得到更多或更少的效益；或者是否早期停止了一批隨機對照試驗對結果有影響。一個正在進行的個別病人數據的統合分析也許可以解決這些議題。

翻譯人

本摘要由臺北榮民總醫院黃筑筠翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

這個系統回顧的結果建議手術前化學治療比起單獨手術治療可能增加非小細胞肺癌病人的存活。不過，需要個別病人資料的系統性回顧和統合分析給我們更可靠的效益規模評估和探索是否特定類型的病人能從手術前化學治療得到更多或更少的效益。