Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases.
Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases.
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DOI：
10.1038/s41598-021-97566-z
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发表时间：
2021-09-13
影响因子：
4.6
通讯作者：
Ahluwalia MS
中科院分区：
文献类型：
--
作者：
Lauko A;Kotecha R;Barnett A;Li H;Tatineni V;Ali A;Patil P;Mohammadi AM;Chao ST;Murphy ES;Angelov L;Suh JH;Barnett GH;Pennell NA;Ahluwalia MS
Immune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p < 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials.
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DOI：
10.1097/jto.0000000000000007
发表时间：
2013-12
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Guin S;Ru Y;Wynes MW;Mishra R;Lu X;Owens C;Barn AE;Vasu VT;Hirsch FR;Kern JA;Theodorescu D
通讯作者：
Theodorescu D
影响因子：
45.3
作者：
Sperduto, Paul W.;Mesko, Shane;Mehta, Minesh P.
通讯作者：
Mehta, Minesh P.
影响因子：
51.1
作者：
Yamamoto, Masaaki;Serizawa, Toru;Tsuchiya, Kazuhiro
通讯作者：
Tsuchiya, Kazuhiro
影响因子：
3.7
作者：
Kim H;Kwon HJ;Park SY;Park Y;Park E;Chung JH
通讯作者：
Chung JH
影响因子：
15.9
作者：
Kotecha, Rupesh;Kim, Joseph M.;Ahluwalia, Manmeet S.
通讯作者：
Ahluwalia, Manmeet S.