Dr. Peters: I had the opportunity to discuss two trials. The first one is the analysis of patients who continue atezolizumab beyond progression in the OAK trial. This large phase III trial compared atezolizumab to docetaxel in the second-line. Basically, 40% of these patients on atezolizumab continued therapy beyond progression. It was a decision of the investigators that if the patient was well and the investigators thought it was OK, the patient would continue therapy. In other trials, like POPLAR, continuation beyond progression provides a real benefit in some patients. It is a small number, maybe 5-10% of those who continue beyond progression, which represents 1-3% of patients given immunotherapy. But these patients do amazingly well, showing benefit for years. The problem is that these patients cannot be identified, as benefit dies but seem to be related to PD-L1 expression or any other marker, other than by using your clinical skills. The patient will tell you they are feeling better even if there is progression. Looking at the other patients, maybe half of the other patients in the clinical trials can continue beyond progression with stable disease. This is OK, because you want to gain more time, but it is not long lasting, maybe 2-3 months. So the majority of patients can continue beyond progression on atezolizumab or another drug maybe for two months. The second trial is KEYNOTE-024. We saw an update of overall survival and a somewhat strange analysis of what they call PFS2, meaning they really want to see the impact of the next line of treatment. The message is that overall survival is still very significant and that the strategy of starting with immunotherapy is the good one. This is also proven by the PFS2 because PFS2 is strongly impacted by PFS1 with the addition of second line treatment activity. This is strikingly better for pembrolizumab compared to chemo. We have seen this in other small trials that chemo probably works better after immunotherapy than before it. So when hesitating as to whether to use docetaxel first or immunotherapy first, we now know that immunotherapy should be first in all circumstances.
瑞士洛桑大学Solange Peters, MD, PhD在6月6日的肺癌口头报告专场上点评了KEYNOTE-024和OAK研究结果(摘要编号9000和9001)。以下分享了她对这两项研究最新报道的见解。
Solange Peters:我在ASCO会议上点评了两项研究。OAK研究是采用Atezolizumab对比多西他赛用于非小细胞肺癌(NSCLC)2-3线治疗的规模最大的研究(n=850)。ASCO报告了晚期NSCLC接受Atezolizumab治疗疾病进展(PD)后继续用药的疗效分析。在332例Atezolizumab治疗PD患者中,51%(168例)在进展后继续接受Atezolizumab治疗。研究者根据患者情况决定其是否适合继续治疗。PD后继续使用Atezolizumab治疗患者的中位OS为12.7个月。在POPLAR等试验中,RECIST进展后继续Atezolizumab治疗给患者带来获益,但比例很小,只有5%~10%,占所有免疫治疗患者的1%~3% 。但是患者的生存获益时间惊人的好。问题是我们无法确认PD后能从继续免疫治疗获益的患者人群,似乎与PD-L1表达或其他标志物相关,而不是靠临床技能辨认。有时尽管疾病进展,患者却感觉良好。在其他临床试验中,半数患者PD后可以继续免疫治疗且疾病稳定,但是获益并不长久,约为2~3个月。因此大部分患者PD可以继续Atezo(或其他免疫抗体)治疗2个月。
ASCO报道了Keynote-024研究中PD-L1肿瘤比例评分(TPS)≥50%的晚期NSCLC在Pembrolizumab进展后接受后线治疗的PFS(PFS2)和OS更新(摘要9000)。Pembrolizumab组的更新OS仍显著优于化疗组,说明一线使用免疫治疗是很好的治疗策略,这也被PFS2数据证实,因为PFS2严重受到PFS1的影响。Pembrolizumab组的PFS2显著优于化疗组。其他小型的临床试验也证实,化疗用于免疫治疗之后比之前的效果好。所以对于符合条件的患者,不用犹豫是先用Pembrolizumab还是先用多西他赛,在任何情况下都应该先给予患者免疫治疗。