Abstract

Background

The use of steroids at baseline before ICI initiation has been associated with poor outcomes, particularly when their indication is related to cancer symptoms. It is poorly known if the initiation of steroids during the course of ICI impacts the outcomes.

Methods

Retrospective analysis of advanced NSCLC patients treated with ICI at Institute Gustave Roussy. Eligible: steroids-naïve at baseline, initiating steroids therapy (≥10 mg of prednisone-equivalent) within the first 8 weeks of ICI. We correlated steroid use with outcomes, including progression-free survival (PFS) and overall survival (OS).

Results

In an overall population of 424 patients treated with ICI, 250 were steroids-naïve at baseline. The median age was 63 years (range 30–92), most of them were male (65.5%), current or former smoker (90.6%), with non-squamous histology (76.1%) and ECOG PS 0/1 (76.8%). A total of 49 patients received early steroids: 39 patients for cancer-related indications [dyspnea (50%), brain metastasis (15.8%), pain (7.9%), superior vena cava syndrome (7.9%), fatigue (5.3%) and others (13.1%)]. For the 10 others indications were: immune-related adverse events (54.6%), COPD exacerbation (27.1%) and others (18.2%). Median (m) PFS and OS were 1.9 months (mo.) [95% CI, (1.77-2.40)] and 10 mo. [95% CI, (8.11-12.91)], respectively. Early introduction of steroids under ICI was associated with a shorter median (m) PFS (1.3 mo., P < 0.0001), and mOS (2.3 mo., P < 0.0001). Patients receiving steroids for cancer-related symptoms had significantly poorer outcomes with mPFS of 1.1 mo. [95% CI, 0.85-1.51] and mOS of 1.9 mo. [95% CI, (1.54-2.4)]. No differences were observed between the group of patients that started steroids for other indications [mPFS 2.7 mo. (1.21-NR); mOS 13.4 mo., (4.30-NR)] and the group without steroids [mPFS 2.6 mo. (2.20-3.94); mOS 13.8 mo. (11.4-18)]. Early steroids introduction for cancer-related symptoms was an independent prognostic factor for both poor PFS [HR 3.04; 95% CI, (1.38-6.66); P = 0.006] and OS [HR 1.21; 95%CI, (0.53-2.8); P < 0.0001].

Conclusion

Introduction of steroids within the first 8 weeks of ICI has no detrimental impact on prognosis if the indication is not related to cancer symptoms.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L. Mezquita: Advisory / Consultancy: Roche Diagnostics; Speaker Bureau / Expert testimony: Bristol-Myers; Speaker Bureau / Expert testimony: Squibb; Speaker Bureau / Expert testimony: Tecnofarma; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: AstraZeneca; Travel / Accommodation / Expenses: Bristol-Myers; Travel / Accommodation / Expenses: Squibb; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Chugai; Research grant / Funding (institution), Mentorship Program: AstraZeneca. E. Auclin: Travel / Accommodation / Expenses: Mundipharma. C. Caramella: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Amgen. L. Hendriks: Research grant / Funding (institution): Roche; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Non-remunerated activity/ies, Mentorship Program: AstraZeneca; Non-remunerated activity/ies, Webinars: Quadia. R. Ferrara: Advisory / Consultancy: MSD; Travel / Accommodation / Expenses: Pfizer. P. Lavaud: Travel / Accommodation / Expenses: Astellas-Pharma; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Janssen Oncology; Travel / Accommodation / Expenses: Mundi Pharma. A. Gazzah: Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Aduro Biotech; Research grant / Funding (institution): Agios Pharmaceuticals; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Argen-X Bvba; Research grant / Funding (institution): Arno Therapeutics; Research grant / Funding (institution): Astex Pharmaceuticals; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Aveo; Research grant / Funding (institution): Bayer Healthcare Ag; Research grant / Funding (institution): Bbb Technologies Bv; Research grant / Funding (institution): Beigene; Research grant / Funding (institution): Bioalliance Pharma; Research grant / Funding (institution): Biontech Ag; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Bristol Myers Squibb; Research grant / Funding (institution): Celgene Corporation; Research grant / Funding (institution): Chugai Pharmaceutical Co.; Research grant / Funding (institution): Clovis Oncology, Daiichi Sankyo, Debiopharm S.A., Eisai, Exelixis, Forma, Gamamabs, Genentech, Inc., Gilead Sciences, Inc, Glaxosmithkline, Glenmark Pharmaceuticals, H3 Biomedicine, Inc, Hoffmann La Roche Ag, Incyte Corporation, Innate Pharma, Iris Servie; Research grant / Funding (self): Janssen Cilag; Non-remunerated activity/ies, Drug Supplied: AstraZeneca, Bayer, Bristol-Myers Squibb, Boringher Ingelheim, Johnson & Johnson, Lilly, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche. J. Adam: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Honoraria (self): MSD; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Takeda; Honoraria (self): Chugai. D. Planchard: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: prIME Oncology; Advisory / Consultancy: Peer CME; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Medimmun; Research grant / Funding (institution): Sanofi-Aventis; Research grant / Funding (institution): Taiho Pharma; Research grant / Funding (institution): Novocure. N. Chaput: Research grant / Funding (institution): Cytune Pharma, GSK, Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Sanofi. B. Besse: Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Biogen; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): IPSEN; Research grant / Funding (institution): Merck KGaA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Onxeo; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Pharma Mar; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Spectrum Pharmaceuticals; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Tiziana Pharma. All other authors have declared no conflicts of interest.

中文翻译：

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46O早期引入类固醇对晚期非小细胞肺癌患者免疫检查点抑制剂（ICI）的影响

抽象的

背景

在开始ICI之前在基线使用类固醇与不良预后相关，尤其是当它们的适应症与癌症症状有关时。尚不清楚在ICI过程中类固醇​​的启动是否会影响预后。

方法

回顾性分析古斯塔夫·鲁西研究所接受ICI治疗的晚期NSCLC患者。合格：在基线时未接受过类固醇治疗，在ICI的前8周内开始类固醇治疗（≥10 mg泼尼松当量）。我们将类固醇的使用与结局相关联，包括无进展生存期（PFS）和总体生存期（OS）。

结果

在424位接受ICI治疗的患者中，有250位在基线时未接受过类固醇治疗。中位年龄为63岁（范围为30-92），其中大多数为男性（65.5％），现在或以前的吸烟者（90.6％），非鳞状组织学（76.1％）和ECOG PS 0/1（76.8％）。 ）。共有49例患者接受了早期激素治疗：39例因癌症相关的适应症[呼吸困难（50％），脑转移瘤（15.8％），疼痛（7.9％），上腔静脉综合征（7.9％），疲劳（5.3％）和其他（13.1％）]。其他10个适应症包括：免疫相关不良事件（54.6％），COPD恶化（27.1％）和其他（18.2％）。PFS和OS的中位数（m）为1.9个月（mo。）[95％CI，（1.77-2.40）]和10 mo。分别为[95％CI（8.11-12.91）]。在ICI下早期引入类固醇与较短的中位（m）PFS（1.3 mo。，P <0.0001）和mOS（2.3 mo。，P <0）有关。0001）。接受类固醇激素治疗癌症相关症状的患者预后较差，mPFS为1.1 mo。[95％CI，0.85-1.51]和1.9 mo的mOS。[95％CI，（1.54-2.4）]。在开始使用类固醇用于其他适应症的患者组之间没有观察到差异[mPFS 2.7 mo。（1.21-NR）；mOS 13.4 mo。，（4.30-NR）]和不含类固醇的组[mPFS 2.6 mo。（2.20-3.94）；mOS 13.8个月 （11.4-18）]。早期引入类固醇以治疗与癌症相关的症状是不良PFS的独立预后因素[HR 3.04; 95％CI（1.38-6.66）; P = 0.006]和OS [HR 1.21; 95％CI（0.53-2.8）; P <0.0001]。在开始使用类固醇用于其他适应症的患者组之间没有观察到差异[mPFS 2.7 mo。（1.21-NR）；mOS 13.4 mo。，（4.30-NR）]和不含类固醇的组[mPFS 2.6 mo。（2.20-3.94）；mOS 13.8个月 （11.4-18）]。早期引入类固醇以治疗与癌症相关的症状是不良PFS的独立预后因素[HR 3.04; 95％CI（1.38-6.66）; P = 0.006]和OS [HR 1.21; 95％CI（0.53-2.8）; P <0.0001]。在开始使用类固醇用于其他适应症的患者组之间没有观察到差异[mPFS 2.7 mo。（1.21-NR）；mOS 13.4 mo。，（4.30-NR）]和不含类固醇的组[mPFS 2.6 mo。（2.20-3.94）；mOS 13.8个月 （11.4-18）]。早期引入类固醇以治疗与癌症相关的症状是不良PFS的独立预后因素[HR 3.04; 95％CI（1.38-6.66）; P = 0.006]和OS [HR 1.21; 95％CI，（0.53-2.8）；P <0.0001]。

结论

如果适应症与癌症症状无关，则在ICI的前8周内引入类固醇对预后没有不利影响。

负责研究的法人实体

作者。

资金

尚未收到任何资金。

揭露

L. Mezquita：咨询/顾问：Roche Diagnostics；发言人办公室/专家证词：百时美施贵宝；发言人办公室/专家证词：Squibb；发言人局/专家证词：Tecnofarma；发言人小组/专家证词：罗氏；发言人小组/专家证词：阿斯利康；旅行/住宿/费用：百时美施贵宝；旅行/住宿/费用：Squibb；旅行/住宿/费用：罗氏；差旅/住宿/费用：中外；研究资助/资助（机构），指导计划：阿斯利康。E. Auclin：差旅/住宿/费用：Mundipharma。C. Caramella：咨询/顾问：Bristol-Myers Squibb；咨询/顾问：MSD；咨询/顾问：罗氏；咨询/顾问：阿斯利康；咨询/顾问：安进。亨德里克斯（L. Hendriks）：研究资助/资助（机构）：罗氏（Roche）；研究资助/资助（机构）：勃林格殷格翰；研究资助/资助（机构）：阿斯利康；咨询/顾问：勃林格殷格翰公司；咨询/顾问：百时美施贵宝；旅行/住宿/费用：罗氏；旅行/住宿/费用：百时美施贵宝；无偿活动，指导计划：阿斯利康；无偿活动，网络研讨会：Quadia。R. Ferrara：咨询/顾问：MSD；旅行/住宿/费用：辉瑞。P. Lavaud：旅行/住宿/费用：Astellas-Pharma；旅行/住宿/费用：阿斯利康；差旅/住宿/费用：伊普森；旅行/住宿/费用：詹森肿瘤学；旅行/住宿/费用：Mundi Pharma。A. Gazzah：研究补助金/资金（机构），差旅/住宿/费用：勃林格殷格翰 咨询/顾问，研究补助金/资金（自己），研究补助金/资金（机构），差旅/住宿/费用：诺华；研究补助金/资金（自己），研究补助金/资金（机构），差旅/住宿/费用：辉瑞公司；研究补助金/资金（自己），研究补助金/资金（机构），差旅/住宿/费用：罗氏；研究经费/资助（机构）：Aduro Biotech；研究经费/资助（机构）：Agios Pharmaceuticals；研究补助金/资金（机构）：Amgen；研究经费/资助（机构）：Argen-X Bvba；研究资助/资助（机构）：Arno Therapeutics; 研究经费/资助（机构）：Astex Pharmaceuticals；研究补助金/资金（自己），研究补助金/资金（机构）：阿斯利康；研究资助/资助（机构）：Aveo；研究资助/资助（机构）：Bayer Healthcare Ag；研究资助/资助（机构）：Bbb Technologies Bv; 研究经费/资助（机构）：Beigene；研究资助/资助（机构）：Bioalliance Pharma; 研究资助/资助（机构）：Biontech Ag；研究经费/资助（机构）：蓝图医学；研究资助/资助（机构）：Bristol Myers Squibb；研究补助金/经费（机构）：Celgene Corporation；研究补助金/经费（机构）：中外制药株式会社；研究资助/资助机构（机构）：Clovis肿瘤学，第一三共制药，Debiopharm SA，卫材，Exelixis，Forma，Gamamabs，Genentech，Inc.，Gilead Sciences，Inc. Incyte Corporation，天赋药业，Iris Servie；研究资助/资助（自己）：Janssen Cilag；无偿活动，提供的药物：阿斯利康，拜耳，百时美施贵宝，博林格·英格海姆，强生，礼来，Medimmune，默克，NH TherAGuiX，辉瑞，罗氏。J. Adam：咨询/顾问：阿斯利康；咨询/顾问：拜耳；Honoraria（个体）：MSD; Honoraria（个体）：百时美施贵宝（Bristol-Myers Squibb）; Honoraria（个体）：百时美施贵宝（Bristol-Myers Squibb）; Honoraria（个体）：武田; Honoraria（个体经营）：Chugai。D. Planchard：酬金（自己），咨询/顾问，研究补助金/资金（机构），差旅/住宿/费用：阿斯利康；酬金（个体经营），咨询/顾问，研究经费/资助（机构）：Bristol-Myers Squibb；酬金（个体经营），咨询/顾问，研究经费/资助（机构）：勃林格殷格翰公司；酬金（个体经营），咨询/顾问：Celgene；咨询/顾问，研究资助/资助（机构）：第一三共；酬金（个体经营），咨询/顾问，研究经费/资助（机构）：礼来；酬金（个体经营），咨询/顾问，研究经费/资助（机构）：默克；酬金（个体经营），咨询/顾问，研究补助金/资金（机构），差旅/住宿/费用：诺华；酬金（个体经营），咨询/顾问，研究经费/资助（机构）：Pfizer；酬金（个体经营），咨询/顾问，差旅/住宿/费用：prIME肿瘤学；咨询/顾问：同级CME；酬金（个体经营），咨询/顾问，研究经费/资助（机构），差旅/住宿/费用：Roche；研究补助金/经费（机构）：Medimmun；研究资助/资助（机构）：Sanofi-Aventis；研究补助金/资金（机构）：Taiho Pharma；研究补助金/经费（机构）：无书。N. Chaput：研究资助/资助（机构）：Cytune Pharma，GSK，赛诺菲；咨询/顾问，发言人局/专家证词：阿斯利康；发言人办公室/专家证词：赛诺菲。B.贝斯：研究资助/资助（机构）：AbbVie；研究补助金/资金（机构）：Amgen；研究资助/资助（机构）：阿斯利康；研究补助金/资金（机构）：Biogen；研究资助/资助（机构）：蓝图药物；研究资助/资助（机构）：Bristol-Myers Squibb；研究补助金/资金（机构）：Celgene；研究经费/资助（机构）：礼来公司；研究资助/资助（机构）：GSK；研究补助金/资金（机构）：Ignyta；研究资助/资助（机构）：IPSEN；研究补助金/资金（机构）：默克（Merck KGaA）；研究经费/资助（机构）：MSD；研究补助金/资金（机构）：Nektar；研究资助/资助（机构）：Onxeo；研究补助金/资金（机构）：辉瑞公司；研究资助/资助（机构）：Pharma Mar；研究经费/资助（机构）：赛诺菲；研究经费/资助（机构）：Spectrum Pharmaceuticals；研究补助金/经费（机构）：武田；研究资助/资助（机构）：Tiziana Pharma。所有其他作者都声明没有利益冲突。研究补助金/资金（机构）：Nektar；研究经费/资助（机构）：Onxeo；研究补助金/资金（机构）：辉瑞公司；研究资助/资助（机构）：Pharma Mar；研究经费/资助（机构）：赛诺菲；研究经费/资助（机构）：Spectrum Pharmaceuticals；研究补助金/经费（机构）：武田；研究资助/资助（机构）：Tiziana Pharma。所有其他作者都声明没有利益冲突。研究补助金/资金（机构）：Nektar；研究经费/资助（机构）：Onxeo；研究补助金/资金（机构）：辉瑞公司；研究资助/资助（机构）：Pharma Mar；研究经费/资助（机构）：赛诺菲；研究经费/资助（机构）：Spectrum Pharmaceuticals；研究补助金/经费（机构）：武田；研究资助/资助（机构）：Tiziana Pharma。所有其他作者都声明没有利益冲突。