在转移性乳腺癌试验中，总生存期（OS）一直被认为是最重要的临床终点。然而，在后续治疗非常有效的时代，生存期还会受到疾病进展后治疗的影响。2014年美国临床肿瘤学学会主办的乳腺癌研讨会上，由Jacques Raphael等人汇报了一项名为“转移性乳腺癌总生存期：我们是否以正确的方式使用了正确的评估终点？”的一项研究。
研究方法：
研究人员应用PubMed搜索了近20年来（1994～2014）发表的III期随机试验，这些试验评估转移性乳腺癌生存期结果。研究人员们调查了试验中进展后的临床结果和进展后患者对治疗的反应/抵抗的报道。
研究结果：
一共有110项试验符合标准：其中69项试验（63%）评估了化疗方案的疗效（A组），27项试验（25%）评估了靶向治疗的疗效（B组），14项试验（13%）评估了内分泌治疗的疗效（C组）。
绝大多数试验将总生存期作为主要或次要评价终点，其中A组97%（66/69），B组100%（27/27），C组86%（12/14）。每组中大约有22%的试验显示总生存期延长。A组1%（1/69）、B组4%（1/27）和C组7%（1/14）的试验报道并讨论了进展后生存期及其对总生存期的影响。
A组和B组中少于10%的试验报道了疾病进展后再次缓解的数据以及缓解的持续时间。此外，只有A组中3%（2/69）的试验报道了进展后治疗的抵抗。此外，A组中14%（10/69）的试验、B组中11%（3/27）的试验和C组中14%（2/14）的试验报道了进展后治疗的次数。
研究结论：
绝大多数转移性乳腺癌的III期试验中明显缺少进展后的治疗信息。我们都知道总生存期直接受进展后治疗的影响。为了评价一种新药的真正的临床疗效并彻底评估总生存期的结果，我们需要详细收集进展后的治疗信息，并在转移性乳腺癌的临床试验中强制执行。
阅读研究原文：
Overall survival (OS) in metastatic breast cancer (MBC): Are we using the right endpoint in the right way?
Background: OS has been historically considered the most important clinical endpoint in MBC trials; however survival could be influenced by treatment after progression in an era of effective subsequent-line agents.
Methods: We conducted a search strategy using PubMed for randomized phase 3 trials published in the last 2 decades (1994-2014) evaluating survival outcome in MBC. We investigated the frequency of trials reporting post progression outcome and response/resistance to treatment beyond progression.
Results: 110 trials met our eligibility criteria: 69 (63%) evaluated chemotherapy regimens (group A), 27 (25%) evaluated targeted therapy (group B) and 14 (13%) focused on endocrine treatment (group C). The majority of the trials had OS as a primary or secondary endpoint (97% (66/69), 100% (27/27) and 86% (12/14) of the trials in group A, B and C respectively). An OS benefit was demonstrated in approximately 22% of the trials in each group. Post progression survival (PPS) and its effect on OS was reported and discussed in only 1% (1/69), 4% (1/27) and 7% (1/14) of the trials for group A, B and C respectively. Less than 10% of the trials in group A and B reported response data and duration of response after progression on trial therapy. In addition, post progression treatment resistance was only reported in group A in 3% (2/69) of the trials. Furthermore, the number of lines of treatment used post progression was reported in only 14% (10/69), 11% (3/27) and 14% (2/14) of the trials in group A, B and C respectively.
Conclusions: A clear paucity of post progression treatment information is noted in the majority of the phase 3 trials for MBC. We do know that OS is directly affected by treatments used after progression. In order to assess the true clinical benefit of a new drug and a complete evaluation of overall survival outcome, a detailed collection of post progression treatment information is required and should be mandated in MBC clinical studies.
