Phase II trial combining atezolizumab concurrently with chemoradiation therapy in locally advanced non-small cell lung cancer.
Phase II trial combining atezolizumab concurrently with chemoradiation therapy in locally advanced non-small cell lung cancer.
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结合 atezolizumab 与放化疗同时治疗局部晚期非小细胞肺癌的 II 期试验。
DOI：
10.1200/jco.2019.37.15_suppl.8512
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发表时间：
2019
影响因子：
45.3
通讯作者：
A. Tsao
中科院分区：
文献类型：
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作者：
Steven H. Lin;Y. Lin;Isabel Mok;J. Young;S. Phan;A. Sandler;V. Papadimitrakopoulou;J. Heymach;A. Tsao
8512背景：化疗后巩固的杜伐单抗(CRT)是局部晚期非小细胞肺癌(LA-NSCLC)治疗的新标准。我们假设，在CRT(CCRT)的同时增加免疫治疗将提高疗效，而不会有明显的相加毒性。为了验证这一概念，我们进行了名为威慑的II期试验，将阿替唑单抗(ATEZO)与CCRT相结合，然后将全剂量卡铂/紫杉醇(CP)与阿泰佐(CP-ATEZO)合并2个周期，然后维持阿泰佐1年。主要终点是安全性/毒性和可行性。方法：本研究从2016年2月至2018年4月，分两部分进行：第一部分(N=10)：常规分割CRT(60-66Gy30-33次联合每周低剂量CP)，然后进行CP-atezo和维持性治疗。第2组为CCRT(N=30)，先给药，然后是CP-药，然后是维持剂。阿特佐静脉滴注1200 mg，q3周。严重不良事件(SAE)≥3级由CTCAEV5.0定义。可评估的受试者接受了至少一剂泰索。PD-L1染色采用DAKO 22C3平台。Kaplan Meier对无进展生存期(PFS)和总生存期(OS)进行分析，并对复发的PD-L1水平进行卡方检验，差异有统计学意义(P<0.05)。结果：在第一部分中，4例(40%)患者出现膝关节相关SAE，其中3级关节痛2例，3级呼吸困难1例，5级TE瘘1例。放射性肺炎(RP)2级1分。在第二部分中，7例(23%)患者出现了与肠易激相关的SAE(腹泻、肾炎、呼吸困难、疲劳和心力衰竭)。RP3例，2例2级，1例3级，导致特佐停用。在第一部分，总体中位随访期(f/u)为22.5个月，幸存者为27.4个月，1年PFS为50%，OS为79%。在第二部分中，生存者的中位F/U时间为11.8个月和13.7个月，1年PFS为57%，OS为79%。34例患者可评估基线肿瘤活检PD-L1状态。PD-L1+Lt；1%(7/16=44%)与≥1%(6/18=33%)、PD-L1切断值50%(11/26=42%)与≥50%(2/8=25%)的肿瘤复发率无显著差异。结论：与单纯CRT、CP-ATEZO和维持性ATEZO相比，同时使用ATEZO和CRT、CP-ATEZO和维持性ATEZO是安全的，且不增加毒性。来自威慑的最新疗效结果将被公布。最终，需要在更大的随机试验中将CCRT免疫疗法和巩固化疗免疫疗法的临床益处与Pacific方案进行比较。临床试验信息：NCT02525757。
8512 Background: Consolidation durvalumab after chemoradiation (CRT) is the new standard of care in locally advanced NSCLC (LA-NSCLC). We hypothesized that adding immunotherapy concurrently with CRT (cCRT) would increase efficacy without significant additive toxicity. To test this concept, we conducted a phase II trial called DETERRED combining atezolizumab (atezo) with cCRT followed by consolidation full dose carboplatin/paclitaxel (CP) with atezo (CP-atezo) for 2 cycles and then maintenance atezo for 1 year. The primary endpoint was safety/toxicity and feasibility. Methods: This study enrolled patients (pts) between February 2016 - April 2018 and was done in two parts: In part 1 (N=10), conventionally fractionated CRT (60-66 Gy in 30-33 fractions combined with weekly low dose CP) was followed by CP-atezo then maintenance atezo. Part 2 was cCRT (N=30) with atezo followed by CP-atezo then maintenance atezo. Atezo was given at 1200 mg IV Q3 weeks. Severe adverse events (SAEs) ≥ grade 3 were defined by CTCAE v5.0. Evaluable pts received at least one dose of atezo. PD-L1 staining utilizes the DAKO 22C3 platform. Kaplan Meier were analyzed for progression free survival (PFS) and overall survival (OS), and chi-square test for PD-L1 levels on any recurrence, with significance set at <0.05. Results: In Part 1, atezo related SAEs were seen in 4 pts (40%) (2 grade 3 arthralgia, 1 grade 3 dyspnea and 1 grade 5 TE fistula). Grade 2 radiation pneumonitis (RP) was seen in 1 pt. In Part 2, seven (23%) pts had atezo related SAEs (diarrhea, nephritis, dyspnea, fatigue and heart failure). RP was seen in 3 pts, 2 grade 2 and 1 grade 3, which led to atezo discontinuation. In Part 1, with an overall median follow up (f/u) time of 22.5 months and 27.4 months for survivors, the 1-year PFS is 50%, and OS is 79%. In part 2, with a median f/u time of 11.8 months and 13.7 months for survivors, the 1-year PFS was 57%, and OS is 79%. Baseline tumor biopsy PD-L1 status was evaluable for 34 pts. There were no significant differences in cancer recurrence for PD-L1 <1% (7/16=44%) vs ≥1% (6/18=33%), or for the PD-L1 cutoff of <50% (11/26=42%) vs ≥50% (2/8=25%). Conclusions: Concurrent atezo with CRT followed by CP-atezo and maintenance atezo is safe without increased toxicities compared to CRT alone followed by CP-atezo and maintenance atezo. Updated efficacy results from DETERRED will be presented. Ultimately, the clinical benefit of immunotherapy with cCRT followed by consolidation chemo-immunotherapy will need to be compared to the PACIFIC regimen in a larger randomized trial. Clinical trial information: NCT02525757.