Clin Cancer Res:中性粒细胞/淋巴细胞比值(NLR)与avelumab联合阿昔替尼或舒尼替尼治疗晚期肾细胞癌(RCC)疗效的关系: 来自JAVELIN Renal 101研究

2021-11-28 yd2015 MedSci原创

研究表明,NLR可作为晚期肾细胞癌(RCC)患者接受avelumab联合阿昔替尼或舒尼替尼治疗的预后标志物。

JAVELIN Renal 101临床研究中,研究PD-L1抑制剂avelumab联合axitinib(阿昔替尼)对比sunitinib(舒尼替尼)治疗既往未治的晚期肾细胞癌(RCC)患者的疗效和安全性。第一次数据分析时,与舒尼替尼相比,avelumab + axitinib显著改善患者的PFS (HR, 0.69;95%CI,0.56-0.84;P<0.001),截止数据时OS数据不成熟(HR, 0.78;95%CI,0.55-1.08;P = 0.14)。联合治疗的客观缓解率(ORR)是舒尼替尼的两倍(51.4% [95% CI, 46.6-56.1] vs 25.7% [95% CI, 21.7-30.0])。近期,研究者基于JAVELIN Renal 101研究评估中性粒细胞/淋巴细胞比值(NLR)与avelumab联合阿昔替尼或舒尼替尼治疗疗效的关系。相关结果发表在CLINICAL CANCER RESEARCH杂志上。

通过对JAVELIN Renal 101临床研究 (NCT02684006)的分析,对avelumab联合阿昔替尼或舒尼替尼组的基线NLR与无进展生存期(PFS)和总生存期(OS)之间的关系进行了回顾性分析。多因素Cox回归分析PFS和OS相关因素。

在avelumab+阿昔替尼组的434例患者和sunitinib组的439例患者中,NLR是可评估的。Avelumab+阿昔替尼组组的中位NLR为2.8(范围,0.5-24.3),sunitinib组的中位NLR为2.8(范围,0.4-41.0)。总体人群中NLR的中位数为2.8(范围0.4-41.0)。

在两治疗组中, 均观察到低-中位NLR患者的PFS较中位-高NLR患者的明显延长。Avelumab+阿昔替尼组的HR=0.85 (95% CI,0.634-1.153),而舒尼替尼组的HR=0.56 (95% CI, 0.415-0.745)。Avelumab+阿昔替尼组低-中位NLR和中位-高NLR患者的中位PFS为13.8个月 (95% CI, 11.1 to NE) 和13.3个月(95% CI, 8.4 to NE)。而舒尼替尼组的分别为11.2个月(95% CI, 8.4-18.6)和5.6个月 (95% CI, 4.3-7.2)。Avelumab+阿昔替尼组低-中位NLR和中位-高NLR患者的12个月无事件发生率为56.4% (95% CI, 48.3%-63.7%)和50.6% (95% CI,42.6%-58.1%)。而舒尼替尼组的分别为49.0% (95% CI, 40.4%-57.0%)和33.2% (95% CI, 25.6%-41.1%)。中位-高NLR患者中,avelumab+阿昔替尼组对比舒尼替尼组PFS的HR=0.60 (95% CI, 0.455-0.782)。

             PFS

在两治疗组中, 均观察到低-中位NLR患者的OS较中位-高NLR患者的明显延长。Avelumab+阿昔替尼组的HR= 0.51 (95% CI, 0.300-0.871),而舒尼替尼组的HR= 0.30 (95% CI, 0.174-0.511)。两组的中位OS均未成熟。中位-高NLR患者中,avelumab+阿昔替尼组对比舒尼替尼组OS的HR= 0.69 (95% CI, 0.461-1.037)。

         OS

在两治疗组中, 均观察到低-中位NLR患者的ORR较中位-高NLR患者的明显增高。Avelumab+阿昔替尼组低-中位NLR和中位-高NLR患者的ORR为57.1% (95% CI, 50.3%-63.8%)和47.5% (95% CI, 40.7%-54.3%),完全缓解率分别为5.5%和1.4%。而舒尼替尼组的分别为29.7% (95% CI, 23.7%-36.2%)和22.3% (95% CI,17.0%-28.4%),完全缓解率分别为3.7%和0%。

                  ORR

Avelumab+阿昔替尼组伴有中位-高NLR患者中,低-中位TMB患者和中位-高TMB患者的PFS或OS没有差异。在Avelumab+阿昔替尼组伴有低-中位NLR患者中,低-中位TMB患者和中位-高TMB患者的PFS和OS有差异(PFS:HR=0.63 95% CI,0.369-1.063; P=0.0406;OS:HR=0.35 95% CI, 0.112-1.122; P=0.0333)。在舒尼替尼组中没有观察到差异性。同时,两治疗组中NLR/TMB分类跟ORR无关。

综上,研究表明,NLR可作为晚期肾细胞癌(RCC)患者接受avelumab联合阿昔替尼或舒尼替尼治疗的预后标志物。

原始出处:

Bilen MA, Rini BI, Voss MH, et al. Association of Neutrophil-to-Lymphocyte Ratio With Efficacy of First-Line Avelumab Plus Axitinib vs Sunitinib in Patients with Advanced Renal Cell Carcinoma Enrolled in the Phase 3 JAVELIN Renal 101 Trial. Clin Cancer Res. 2021 Nov 17:clincanres.1688.2021. doi: 10.1158/1078-0432.CCR-21-1688. Epub ahead of print. PMID: 34789480.

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objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1329927, encodeId=edff132992e28, content=<a href='/topic/show?id=e6c99e836f0' target=_blank style='color:#2F92EE;'>#阿昔替尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97836, encryptionId=e6c99e836f0, topicName=阿昔替尼)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/DC48AC6B5FFD609EED5594C15A97B420/100, createdBy=57dc2500034, createdName=ms1692212821629096, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1348515, encodeId=9ac9134851544, content=<a href='/topic/show?id=3c1630303e' target=_blank style='color:#2F92EE;'>#avelumab#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3030, encryptionId=3c1630303e, topicName=avelumab)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=fangcong, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407770, encodeId=7d04140e770c2, content=<a href='/topic/show?id=a22412862b3' target=_blank style='color:#2F92EE;'>#NLR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12862, encryptionId=a22412862b3, topicName=NLR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8cd32710930, createdName=yuandd, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441770, encodeId=0d951441e70db, content=<a href='/topic/show?id=09a6598e57a' target=_blank style='color:#2F92EE;'>#晚期肾细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59875, encryptionId=09a6598e57a, topicName=晚期肾细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=87304889998, createdName=12498c24m70暂无昵称, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=)]
    2022-01-05 isabellayj
  4. 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createdBy=28bc32453681, createdName=jml2020, createdTime=Thu Dec 23 06:19:03 CST 2021, time=2021-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2036742, encodeId=3ee82036e426f, content=<a href='/topic/show?id=3bde1518863' target=_blank style='color:#2F92EE;'>#RCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15188, encryptionId=3bde1518863, topicName=RCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d784426, createdName=isabellayj, createdTime=Wed Jan 05 12:19:03 CST 2022, time=2022-01-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1979249, encodeId=b46819e92496a, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, 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objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65990, encryptionId=82a6659902c, topicName=淋巴细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1e34303, createdName=wetgdt, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1329927, encodeId=edff132992e28, content=<a href='/topic/show?id=e6c99e836f0' target=_blank style='color:#2F92EE;'>#阿昔替尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97836, encryptionId=e6c99e836f0, topicName=阿昔替尼)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/DC48AC6B5FFD609EED5594C15A97B420/100, createdBy=57dc2500034, createdName=ms1692212821629096, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, 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createdBy=8cd32710930, createdName=yuandd, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441770, encodeId=0d951441e70db, content=<a href='/topic/show?id=09a6598e57a' target=_blank style='color:#2F92EE;'>#晚期肾细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59875, encryptionId=09a6598e57a, topicName=晚期肾细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=87304889998, createdName=12498c24m70暂无昵称, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=)]
  5. 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  6. [GetPortalCommentsPageByObjectIdResponse(id=1912727, encodeId=f3ec1912e272b, content=<a href='/topic/show?id=4de7112046c' target=_blank style='color:#2F92EE;'>#mAb#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11204, encryptionId=4de7112046c, topicName=mAb)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=25e7304, createdName=snf701207, createdTime=Mon May 16 12:19:03 CST 2022, time=2022-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1717685, encodeId=4df41e176851b, content=<a href='/topic/show?id=a7ab15318fc' target=_blank style='color:#2F92EE;'>#renal#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15318, encryptionId=a7ab15318fc, topicName=renal)], attachment=null, authenticateStatus=null, createdAvatar=null, 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1348515, encodeId=9ac9134851544, content=<a href='/topic/show?id=3c1630303e' target=_blank style='color:#2F92EE;'>#avelumab#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3030, encryptionId=3c1630303e, topicName=avelumab)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=fangcong, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407770, encodeId=7d04140e770c2, content=<a href='/topic/show?id=a22412862b3' target=_blank style='color:#2F92EE;'>#NLR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12862, encryptionId=a22412862b3, topicName=NLR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8cd32710930, createdName=yuandd, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441770, encodeId=0d951441e70db, content=<a href='/topic/show?id=09a6598e57a' target=_blank style='color:#2F92EE;'>#晚期肾细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59875, encryptionId=09a6598e57a, topicName=晚期肾细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=87304889998, createdName=12498c24m70暂无昵称, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1912727, encodeId=f3ec1912e272b, content=<a href='/topic/show?id=4de7112046c' target=_blank style='color:#2F92EE;'>#mAb#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11204, encryptionId=4de7112046c, topicName=mAb)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=25e7304, createdName=snf701207, createdTime=Mon May 16 12:19:03 CST 2022, time=2022-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1717685, encodeId=4df41e176851b, content=<a href='/topic/show?id=a7ab15318fc' target=_blank style='color:#2F92EE;'>#renal#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15318, encryptionId=a7ab15318fc, topicName=renal)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=28bc32453681, createdName=jml2020, createdTime=Thu Dec 23 06:19:03 CST 2021, time=2021-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2036742, encodeId=3ee82036e426f, content=<a href='/topic/show?id=3bde1518863' target=_blank style='color:#2F92EE;'>#RCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15188, encryptionId=3bde1518863, topicName=RCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d784426, createdName=isabellayj, createdTime=Wed Jan 05 12:19:03 CST 2022, time=2022-01-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1979249, encodeId=b46819e92496a, content=<a href='/topic/show?id=3b90e79787f' target=_blank style='color:#2F92EE;'>#细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, 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  8. [GetPortalCommentsPageByObjectIdResponse(id=1912727, encodeId=f3ec1912e272b, content=<a href='/topic/show?id=4de7112046c' target=_blank style='color:#2F92EE;'>#mAb#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11204, encryptionId=4de7112046c, topicName=mAb)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=25e7304, createdName=snf701207, createdTime=Mon May 16 12:19:03 CST 2022, time=2022-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1717685, encodeId=4df41e176851b, content=<a href='/topic/show?id=a7ab15318fc' target=_blank style='color:#2F92EE;'>#renal#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15318, encryptionId=a7ab15318fc, topicName=renal)], attachment=null, authenticateStatus=null, createdAvatar=null, 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1348515, encodeId=9ac9134851544, content=<a href='/topic/show?id=3c1630303e' target=_blank style='color:#2F92EE;'>#avelumab#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3030, encryptionId=3c1630303e, topicName=avelumab)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b79433, createdName=fangcong, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407770, encodeId=7d04140e770c2, content=<a href='/topic/show?id=a22412862b3' target=_blank style='color:#2F92EE;'>#NLR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12862, encryptionId=a22412862b3, topicName=NLR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8cd32710930, createdName=yuandd, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441770, encodeId=0d951441e70db, content=<a href='/topic/show?id=09a6598e57a' target=_blank style='color:#2F92EE;'>#晚期肾细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59875, encryptionId=09a6598e57a, topicName=晚期肾细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=87304889998, createdName=12498c24m70暂无昵称, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=)]
    2021-11-30 fangcong
  9. 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createdBy=8cd32710930, createdName=yuandd, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441770, encodeId=0d951441e70db, content=<a href='/topic/show?id=09a6598e57a' target=_blank style='color:#2F92EE;'>#晚期肾细胞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59875, encryptionId=09a6598e57a, topicName=晚期肾细胞癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=87304889998, createdName=12498c24m70暂无昵称, createdTime=Tue Nov 30 08:19:03 CST 2021, time=2021-11-30, status=1, ipAttribution=)]
    2021-11-30 yuandd
  10. 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