Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma

 

Abstract

Background

Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed.

Objectives

To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma.

Search methods

We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials.

Selection criteria

All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma.

Data collection and analysis

Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials.

Main results

Eighteen studies met our criteria and were included in the meta-analysis, with a total of 2625 participants. We found evidence of an increase of objective response rates in people treated with chemoimmunotherapy, in comparison with people treated with chemotherapy. Nevertheless, the impact of these increased response rates was not translated into a survival benefit. We found no difference in survival to support the addition of immunotherapy to chemotherapy in the systemic treatment of metastatic melanoma, with a hazard ratio of 0.89 (95% CI 0.72 to 1.11, P = 0.31). Additionally, we found increased hematological and non-hematological toxicities in people treated with chemoimmunotherapy.

Authors' conclusions

We failed to find any clear evidence that the addition of immunotherapy to chemotherapy increases survival of people with metastatic melanoma. Further use of combined immunotherapy and chemotherapy should only be done in the context of clinical trials.

 

Plain language summary

Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma

Malignant melanoma is one of the most aggressive of all skin cancers. If it is confined to the skin, it can often be cured by surgery. However if it has spread, melanoma is usually incurable because it does not respond to most treatments. Recently clinicians have been trying a combination of chemotherapy and immunotherapy in the hope of improving the outcome. The review of trials showed an increased response to treatment when immunotherapy was added to chemotherapy, but no difference was seen in survival rate and toxic effects were increased.

There is not enough evidence to support the use of a combination of combined immunotherapy and chemotherapy in treatment of metastatic malignant melanoma.

 

摘要

背景

針對轉移性惡性黑色素細胞瘤的化學免疫療法與化學療法的比較

惡性黑色素細胞瘤是最常見之具侵略性皮膚腫瘤之一，全世界的發生率正在增加當中。手術是早期惡性黑色素細胞瘤治療方式的基石。但是轉移性惡性黑色素細胞瘤通常無法治癒因為他對於系統性治療通常反應不佳。有一些新奇且具有一定療效的治療方式正在評估當中，但它們通常也伴隨著較高的毒性與花費。有報告指出，與單獨使用化學治療相比，合併化學治療與免疫療法能改善療效，但是是否有足夠之證據來支持這項說法仍未明確。沒有語言限制規定。

目標

比較合併化學治療與免疫療法與單獨使用化學治療，對於治療轉移性惡性黑色素細胞瘤之效果。

搜尋策略

我們搜尋以下資料庫： the Cochrane Skin Group Specialised Register (2006年2月14日), the Cochrane Central Register of Controlled Trials (Cochrane 圖書館第3期，2005年), MEDLINE (2003年至2006年1月30號), EMBASE (2003年至2005年7月20日) and LILACS (1982年至2006年2月20日) 。 參考文獻，會議記錄和正進行中研究的數據庫也被用來定位試驗。

選擇標準

所有隨機對照試驗，比較單獨使用化學治療與合併化學治療及免疫療法在任何年齡層的人，對於治療轉移性惡性黑色素細胞瘤之效果。

資料收集與分析

兩名作者獨立地分析各項研究以評估是否符合之前定義的挑選條件，並藉由與回顧團隊討論以解決差異。兩名作者獨立地利用資料擷取表取得各研究資料。品質分析包括評估多種與療效偏見評估有關的層面。若可能的話，針對所取得的資料做統合分析以計算加權療效。

主要結論

一共有八項研究符合我們的條件並且納入統合分析，共包含了２６２５位病人。我們發現與單獨化學治療相比，在化學免疫療法這一組的客觀治療反應有增加。然而，治療反應增加率的影響力並不足以轉換成較佳的存活率。由於存活率方面並無顯著差異，所以對於轉移性的惡性黑色素瘤而言，免疫療法對於化學療法並無加成作用，hazard ratio 為0.89(95％CI為0.72至1.11，P = 0.31)。此外，化學免疫療法會增加血液與非血液方面的毒性。

作者結論

我們無法找出任何明確的證據來證明合併免疫療法與化學治療能增加轉移性黑色素瘤病人的存活率。之後使用合併化學與免疫療法應納入臨床試驗範疇。

翻譯人

本摘要由馬偕醫院黃景昱翻譯。

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

總結

針對轉移性惡性黑色素細胞瘤的化學免疫療法與化學療法的比較惡性黑色素細胞瘤是所有皮膚癌症中最具侵犯性的癌症之一。若只侷限在皮膚，手術通常可以治癒。然而，一旦黑色素細胞瘤擴散，因為它對大部分治療反應不佳而變得不易治癒。近來臨床醫師試著結合免疫與化療以期待能改善預後。本篇回顧發現加入免疫療法會增加治療的反應，但不能增加存活率，並且毒性反而增加。沒有足夠的證據支持合併使用免疫與化學療法對於轉移性惡性黑色素瘤有幫助。