Revisiting the association between skin toxicity and better response in advanced cancer patients treated with immune checkpoint inhibitors.
Revisiting the association between skin toxicity and better response in advanced cancer patients treated with immune checkpoint inhibitors.
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DOI：
10.1186/s12967-020-02612-5
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发表时间：
2020-11-11
影响因子：
7.4
通讯作者：
Osman I
中科院分区：
文献类型：
--
作者：
Gulati N;Donnelly D;Qian Y;Moran U;Johannet P;Zhong J;Osman I
Immune checkpoint inhibition (ICI) improves survival outcomes for patients with several types of cancer including metastatic melanoma (MM), but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations. To examine the potential confounding impact of such variables, we analyzed advanced cancer patients enrolled prospectively in a clinicopathological database with protocol-driven follow up and treated with ICI. We tested the associations between developing ST, stratified as no (n = 617), mild (n = 191), and severe (n = 63), and progression-free survival (PFS) and overall survival (OS) in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival associating with adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model. Both mild and severe ST were significantly associated with improved PFS and OS (all P < 0.001). However, when adjusting for the time from treatment initiation to time of skin event, severe ST was not associated with PFS benefit both in univariable and multivariable analyses (P = 0.729 and P = 0.711, respectively). Receiving systemic steroids for ST did not lead to significant differences in PFS or OS compared to patients who did not receive systemic steroids. Our data reveal the influence of time to event and its severity as covariates in analyzing the relationship between ST and ICI outcomes. These differences in outcomes cannot be solely explained by the use of immunosuppressive medications, and thus highlight the importance of host- and disease-intrinsic factors in determining ICI response and toxicity. Trial registration: The patient data used in this manuscript come from patients who were prospectively enrolled in two institutional review board-approved databases at NYU Langone Health (institutional review board #10362 and #S16-00122).
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影响因子：
158.5
作者：
Larkin, J.;Chiarion-Sileni, V.;Wolchok, J. D.
通讯作者：
Wolchok, J. D.
影响因子：
28.4
作者：
Eggermont, Alexander M. M.;Kicinski, Michal;Suciu, Stefan
通讯作者：
Suciu, Stefan
影响因子：
28.5
作者：
Marin-Acevedo JA;Dholaria B;Soyano AE;Knutson KL;Chumsri S;Lou Y
通讯作者：
Lou Y
DOI：
10.1158/1078-0432.ccr-15-1136
发表时间：
2016-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Freeman-Keller M;Kim Y;Cronin H;Richards A;Gibney G;Weber JS
通讯作者：
Weber JS
影响因子：
10.9
作者：
Sanlorenzo, Martina;Vujic, Igor;Daud, Adil;Algazi, Alain;Gubens, Matthew;Luna, Sara Alcantara;Lin, Kevin;Quaglino, Pietro;Rappersberger, Klemens;Ortiz-Urda, Susana
通讯作者：
Ortiz-Urda, Susana