编者按：2022年ASCO年会已经圆满落下帷幕，作为世界上规模最大、学术水平最高、最具权威的临床肿瘤学会议，多项研究结果在会上进行了公布。在会上，《肿瘤瞭望》记者采访到了MAINTAIN研究的PI——美国埃默里大学Winship癌症研究所Kevin Kalinsky教授，请他为我们就该项研究背景、研究方法及相关启示进行介绍。

 

肿瘤瞭望：请您为我们介绍一下，MAINTAIN研究开展的背景？

 

Could you please introduce the background of the MAINTAIN trial?

 

Kevin Kalinsky教授：MAINTAIN研究是一项随机对照试验，研究入组对象为HR+/HER2-晚期乳腺癌患者，这些患者至少都经过一种CDK 4/6抑制剂治疗和任何一种内分泌治疗后出现疾病进展。该研究共入组了120例患者，并将患者按照1:1比例进行分配，给予内分泌联合瑞博西利（ribociclib）治疗或内分泌联合安慰剂治疗。

 

 

The MAINTAIN trial was a randomized trial that looked at patients with hormone receptor positive，HER2-negative metastatic breast cancer，who have had tumors that have had progressed on，at least any CDK4/6 inhibitor and any endocrine therapy.Then randomized patients in a 1 to 1 fashion to switching endocrine therapy plus ribociclib versus switching endocrine therapy plus placebo.This total sample size was 120 patients.

 

肿瘤瞭望：该研究将入组患者分为了几部分，分别给予了哪些治疗方案？请您为我们介绍其研究方法。

 

How many groups of patients were enrolled in the trial，and what treatment regimens were they given?Please introduce the research method for us.

 

Kevin Kalinsky教授：在MAINTAIN研究中随机纳入该试验的患者分为两组。一组给予瑞博西利联合内分泌治疗，瑞博西利的剂量为600 mg/m2，每用药三周停一周，另一组则给予安慰剂加内分泌治疗。

 

 

For the patients who were randomized into the trial.There were two cohorts.There was a cohort of patients who received ribociclib at 600 mg/m2，3 weeks on，1 week off，plus endocrine therapy versus placebo plus endocrine therapy.

 

肿瘤瞭望：该项研究中哪组患者的治疗效果更好？在临床实践中，您更推荐哪种治疗方案？

 

Which group of patients had better outcomes in this study?Which treatment regimen do you recommend more in clinical practice?

 

Kevin Kalinsky教授：该研究的主要临床终点是无病进展生存期（PFS），定义为从随机分组到疾病进展或死亡的时间。本次大会上MAINTAIN研究公布的结果显示，与接受安慰剂联合内分泌治疗的患者相比，瑞博西利联合内分泌治疗患者的PFS显示出了具有统计学意义的改善（5.29个月vs.2.76个月），HR=0.57（95CI：0.39～0.95），P=0.006。这些数据也证实了对于CDK4/6抑制剂治疗失败后的患者，再次使用CKD4/6抑制剂（瑞博西利）仍能使患者获益。

 

 

 

该项研究结果目前有两个临床要点需要说明。一是CDK4/6抑制剂联合内分泌治疗后患者获益十分有限，这一点在其他研究中亦有迹可循，如EMERALD和VERONICA研究。另外，这些首次获得的随机数据也证实了CDK4/6抑制剂治疗失败后再次使用CKD4/6抑制剂确有获益。当然，目前也还有其他的随机试验结果等待我们去了解。

 

In the study，the primary endpoint was progression free survival.We saw that MAINTAIN was a positive study for the patients who were randomized ribociclib plus endocrine therapy.They had a statistically significant improvement in progression free survival compared to those who received placebo plus endocrine therapy.The hazard ratio was less than 0.6 and the P value of 0.006.I think these data confirm the hypothesis that there is benefit for CDK4/6 inhibitor after CDK4/6 inhibitor.

 

I think there are two clinical points to make.One is just how limited the response was for patients who got single agent hormone therapy after CDK 4/6 inhibitor，which has been similar to what we’ve seen with other studies，like EMERALD and VERONICA.And these are the first randomized data demonstrating the principle that there’s a benefit for CDK 4/6 inhibitor after CDK 4/6 inhibitor.Understanding that there are other randomized trials that we are waiting to read out.

 

肿瘤瞭望：MAINTAIN研究为HR+晚期乳腺癌患者的治疗带来了哪些启示？

 

What implications does the MAINTAIN study bring to the treatment of HR-positive advanced breast cancer patients?

 

Kevin Kalinsky教授：我认为其意义在于，CDK 4/6抑制剂（的跨线挑战）对于转移性激素受体阳性、HER2阴性乳腺癌患者的治疗是一次巨大变革。我们在多项研究中看到患者总生存率的改善，也看到CDK4/6抑制剂治疗后仅给予内分泌治疗的效果不尽人意。我认为MAINTAIN试验的结果说明我们仍需考虑新药物，如新的内分泌治疗，新的靶向治疗，以及这些疗法的最佳排序，如此，患者可在接受化疗等治疗方式前尽可能长时间地接受内分泌治疗。

 

Now，I think the implications are that we have seen that CDK 4/6 inhibitors have been a real game changer for patients，with metastatic hormone receptor positive，HER2 negative disease.We’ve seen overall survival in a number of studies.We also see that giving just hormonal therapy afterwards has really limited activity.I think this really speaks to the fact that big picture wise that post CDK4/6 inhibition that it’s still important for us to think about newer agents，newer，hormonal therapies，newer，targeted therapies，and then how we’re gonna best sequence those.So that patients can remain on hormone based therapy for as long as possible before they need something like chemotherapy.

 

Kevin Kalinsky

美国埃默里大学Winship癌症研究所乳腺肿瘤医学研究所主任

埃默里大学医学院血液学与肿瘤内科副教授