肿瘤

Pembrolizumab联合铂基化疗治疗复发性EGFR/ alk阳性非小细胞肺癌

作者:zt 来源:医学论坛网 日期:2021-08-30
导读

         Pembrolizumab in Combination With Platinum-Based Chemotherapy in Recurrent EGFR/ALK-Positive Non-Small Cell Lung Cancer (NSCLC) Pembrolizumab联合铂基化疗治疗复发性EGFR/ alk阳性非小细胞肺癌 Introduction 介绍 Efficacy of s

 Pembrolizumab in Combination With Platinum-Based Chemotherapy in Recurrent EGFR/ALK-Positive Non-Small Cell Lung Cancer (NSCLC)

Pembrolizumab联合铂基化疗治疗复发性EGFR// alk阳性非小细胞肺癌

Introduction
介绍

Efficacy of single-agent immune checkpoint inhibitors is limited in patients with EGFR/ALK-altered NSCLC. We conducted a phase II study to assess the efficacy of pembrolizumab in combination with carboplatin and pemetrexed in these patients.

单药免疫检查点抑制剂在EGFR/ alk改变的NSCLC患者中的疗效有限。我们进行了一项II期研究,以评估派姆单抗联合卡铂和培美曲塞在这些患者中的疗效。

Methods
研究方法

Patients with recurrent EGFR-mutated or ALK-rearranged NSCLC, previously treated with targeted therapy, were eligible. Patients were treated with carboplatin AUC5, pemetrexed 500 mg/m2 and pembrolizumab 200 mg I.V. every 3 weeks. After 4 cycles patients were maintained on pemetrexed and pembrolizumab for up to 2 years. Disease was assessed every 2 cycles for the first 6 cycles, then per investigator discretion. The primary end-point was RECIST 1.1 defined response rate. Secondary endpoints included PFS and OS. Tumor PD-L1 expression was assessed locally. Blood for circulating tumor cells (CTCs) was collected prior to the 1st and 3rd cycles. The plan was to enroll 28 evaluable patients in each of two separate cohorts of EGFR-mutated and ALK-rearranged NSCLC. Slow enrollment led to early termination of the trial.

复发性egfr突变或alk重排的NSCLC患者,之前接受过靶向治疗,符合条件。卡铂AUC5,培美曲塞500mg / m2,派姆单抗200mg,每3周静脉注射一次。4个周期后,患者继续使用培美曲塞和派姆单抗长达2年。在前6个周期中每2个周期评估一次疾病,然后由研究人员自行决定。主要终点为RECIST 1.1定义的应答率。次要终点包括PFS和OS。局部检测肿瘤PD-L1表达。循环肿瘤细胞(ctc)血液在1次循环前采集。该研究计划在egfr突变和alk重排NSCLC的两个独立队列中分别纳入28例可评估患者。缓慢的登记导致试验提前终止。

Results

结果

Of the 33 patients enrolled, 26 had EGFR-mutated NSCLC (13 del19, 9 L858R), 64% were female and median age was 67 years. The median number of prior treatments was 1 (range 1-3). 22 of 26 EGFR+ NSCLC patients had received prior osimertinib. Median number of cycles was 6 (2-24 cycles), with 4 patients, all EGFR+, still on therapy. Response rates (95%CI) were 42% (23%, 63%) and 29% (4%, 71%) among EGFR+ and ALK+ patients, respectively. Median duration of response was 6.1 months in all patients and in EGFR+ patients. Other efficacy results are provided below. Tumor PD-L1 expression was available for 30 patients and was ≥ 1% in 17. There was no difference in survival between patients with tumor PD-L1 <1% vs. ≥ 1%. The median CTC count at baseline in 15 EGFR+ patients in whom samples were available was 4/ml (0-23). Median overall survival among EGFR+ patients with decreased vs. increased CTC count during treatment was not reached vs. 18.5 months, respectively (p=0.52 for OS). The most common adverse events were fatigue, nausea, cytopenias, cough and dyspnea. The most common ≥ grade 3 toxicities were neutropenia, thrombocytopenia, thromboembolism, and AST/ALT elevation. One patient developed pneumonitis.

在纳入的33例患者中,26例为egfr突变的NSCLC (13 del19, 9 L858R), 64%为女性,中位年龄为67岁。既往治疗的中位数为1例(范围1-3例)。26例EGFR+ NSCLC患者中有22例既往接受过奥西替尼治疗。中位周期数为6个(2-24个周期),其中4例患者均为EGFR+,仍在治疗中。EGFR+和ALK+患者的缓解率(95%CI)分别为42%(23%,63%)和29%(4%,71%)。所有患者和EGFR阳性患者的中位缓解持续时间为6.1个月。其他疗效结果如下。肿瘤PD-L1表达有30例,其中17例≥1%。肿瘤PD-L1 <1%与≥1%患者的生存期无差异。在15例样本可用的EGFR+患者中,基线时中位CTC计数为4/ml(0-23)。治疗期间CTC计数减少与增加的EGFR+患者的中位总生存期分别为18.5个月(p=0.52 OS)。最常见的不良事件是疲劳、恶心、细胞减少、咳嗽和呼吸困难。最常见的≥3级毒性是中性粒细胞减少、血小板减少、血栓栓塞和AST/ALT升高。1名患者发展为肺炎。

 

EFGR+ (n=26)

ALK+ (n=7)

All (n=33)

Median PFS (months. 95%CI)

8.3 (7.2, 16.5)

2.9 (1.1, NE)

7.3 (5.3, 14.1)

12-month PFS

(95% CI)

29% (14%, 59%)

14% (2%, 88%)

26% (13%, 50%)

Median OS (months, 95% CI)

22.2 (20.6, NE)

2.9 (1.1, NE)

20.6 (10.1, NE)

12-month OS

(95% CI)

76% (59%, 97%)

14% (2%, 88%)

61% (44%, 83%)

Conclusion
结论

Pembrolizumab in combination with chemotherapy demonstrated a response rate of 42% and median survival of 22 months among patients with recurrent EGFR-mutated NSCLC. These results warrant further study of this combination in this patient population.

在复发性egfr突变NSCLC患者中,Pembrolizumab联合化疗的应答率为42%,中位生存期为22个月。这些结果为进一步研究该联合治疗提供了依据。

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