Abstract

Background

ICI has revolutionized the treatment of lung cancer, with new approaches in 1L NSCLC. The aim of this study is to compare the efficacy of treatments that combine chemotherapy (CH) plus a PD1/L1 inhibitor in clinical trials (CT) and the benefits in the different subgroups of patients.

Methods

We performed a searching in Pubmed to identify CT. Key words were: NSCLC, PD1/L1 and CH. All phase III trials that combined CH with an antiPD1/L1 were selected. The results were combined in MA with the corresponding forest plots and presented as Hazard Ratios (HR) and Odds Ratio (OR), with 95% CI. DerSimonian-Laird random effects models for main and subgroup analyses has been implemented.

Results

A total of 86 publications were reviewed, 6 of them met the inclusion criteria with 3,807 patients. 6 pair wise MA was performed. Control arm in all studies was platinum doublet CH. Bevacizumab was added in 1 trial in the control and experimental arm. 4 studies tested an antiPD-1, and 2 antiPD-L1. 2 studies included EGFR/ALK mutated patients (EGFR/ALK+). PFS final data was reported in all the studies and overall survival (OS) in 4. The addition of PD-1/L1 inhibitors was associated with significantly prolonged progression-free survival (PFS) (HR: 0.59, 95% CI: 0.55-0.64, p < 0.001) and OS (HR: 0.75, 95CI: 0.64-0.87; p < 0.001). Women, ≤65 years old, PS 0, never smokers, liver metastasis (mx) and PD-L1 ≥50% were the subgroups with better benefit (table). Just one trial showed PFS and OS improvement in EGFR/ALK+. Numerically better ORR was obtained in the IMpower150 (56.4%) trial for non-squamous (sq) NSCLC and KEYNOTE407 for sq NSCLC (57.9%).

Conclusion

The association of immunotherapy plus CH is a better treatment option for all patients in 1L NSCLC. Standard subgroups are the most benefited, except liver mx patients and EGFR/ALK+ especially benefited for the combination of an antiPD-L1 and an antiVEGF. Table:117P OS by subgroupsHR (CI 95%)Women0.51 [0.32-0.84]Men0.75 [0.64-0.87]<650.62 [0.46-0.84]≥650.74 [0.63-0.87]PS 00.65 [0.49-0.88]PS 10.72 [0.60-0.87]Never smoker0.47 [0.26-0.85]Smoker0.71 [0.56-0.91]No liver mx0.61 [0.55-0.67]Liver mx0.69 [0.46-1.0]PD-L1 H0.66 [0.52-0.82]

Legal entity responsible for the study

The authors.

Funding

Roche Farma S.A.

Disclosure

F.J. Afonso-Afonso: Advisory / Consultancy: Roche; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: IPSEN; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer; Advisory / Consultancy: Takeda; Advisory / Consultancy: Sanofi. M. Amenedo Gancedo: Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Tesaro; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: PharmaMar; Speaker Bureau / Expert testimony: Roche. M.C. Areses Manrique: Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Boehringer. B. Campos Balea: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony: Merck; Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: AstraZeneca; Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer. N. Fernández-Núñez: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: AstraZeneca; Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehinrger; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi. J.L. Firvida Perez: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche. J. García González: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer. M. Lázaro Quintela: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy: GSK; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer; Advisory / Consultancy, Travel / Accommodation / Expenses: Takeda; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Tesaro. L. León-Mateos: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer. J. Ruíz-Bañobre: Advisory / Consultancy: Boehringer; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: IPSEN; Travel / Accommodation / Expenses: PharmaMar; Speaker Bureau / Expert testimony: Roche. D. Pérez Parente: Full / Part-time employment: Roche. L. Crama: Full / Part-time employment: Roche. P. Ruiz Gracia: Full / Part-time employment: Roche. L. Santomé Couto: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Boehringer. All other authors have declared no conflicts of interest.

中文翻译：

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117P免疫检查点抑制剂（ICI）联合化学疗法作为非小细胞肺癌（NSCLC）的一线治疗（1L）：成对荟萃分析（MA）

抽象的

背景

ICI用1L NSCLC的新方法彻底改变了肺癌的治疗方法。这项研究的目的是比较在临床试验（CT）中将化学疗法（CH）与PD1 / L1抑制剂联合使用的治疗效果以及不同亚组患者的获益。

方法

我们在Pubmed中进行了搜索以识别CT。关键词为：NSCLC，PD1 / L1和CH。选择了将CH与抗PD1 / L1联合使用的所有III期试验。结果在MA中与相应的林地结合在一起，以95％CI的危险比（HR）和几率（OR）表示。已实施用于主要和次组分析的DerSimonian-Laird随机效应模型。

结果

共审查了86篇出版物，其中6篇符合入选标准，共有3,807例患者。进行6对MA。在所有研究中，对照组均为铂双峰CH。在一项试验中，在对照组和实验组中添加了贝伐单抗。4项研究测试了抗PD-1和2项抗PD-L1。2项研究包括EGFR / ALK突变患者（EGFR / ALK +）。在所有研究中均报告了PFS最终数据，其中4个报告了总生存期（OS）。PD-1/ L1抑制剂的加入与无进展生存期（PFS）显着延长有关（HR：0.59，95％CI：0.55- 0.64，p <0.001）和OS（HR：0.75，95CI：0.64-0.87; p <0.001）。≤65岁，PS 0，永不吸烟者，肝转移（mx）和PD-L1≥50％的女性是获益更大的亚组（表）。只有一项试验显示EGFR / ALK +的PFS和OS改善。

结论

对于1L NSCLC的所有患者，免疫疗法加CH的联合治疗是更好的治疗选择。除了肝mx患者和EGFR / ALK +尤其受益于抗PD-L1和抗VEGF的组合，标准亚组是受益最大的人群。表：按子组分类的117P OS HR（CI 95％）妇女0.51 [0.32-0.84]男性0.75 [0.64-0.87] <650.62 [0.46-0.84]≥650.74[0.63-0.87] PS 00.65 [0.49-0.88] PS 10.72 [0.60-0.87]从不吸烟者0.47 [0.26-0.85]吸烟者0.71 [0.56-0.91]无肝脏mx0.61 [0.55-0.67]肝脏mx0.69 [0.46-1.0] PD-L1 H0.66 [0.52- 0.82]

负责研究的法人实体

作者。

资金

罗氏法玛公司

揭露

FJ Afonso-Afonso：咨询/顾问：Roche；咨询/顾问：默克；咨询/顾问，旅行/住宿/费用：百时美施贵宝；咨询/顾问，旅行/住宿/费用：阿斯利康；发言人办公室/专家证词：礼来公司；咨询/顾问，差旅/住宿/费用：辉瑞；咨询/顾问：扬森；咨询/顾问，差旅/住宿/费用：IPSEN；咨询/顾问，旅行/住宿/费用：勃林格；咨询/顾问：武田；咨询/顾问：赛诺菲。M. Amenedo Gancedo：咨询/顾问：Clovis肿瘤学；咨询/顾问：Tesaro；发言人小组/专家证词：阿斯利康；发言人局/专家证词：PharmaMar；发言人办公室/专家证词：罗氏（Roche）。MC Areses Manrique：发言人小组/专家证词：罗氏；发言人局/专家证词：默克；咨询/顾问，发言人办公室/专家证词：百时美施贵宝；发言人小组/专家证词：阿斯利康；发言人办公室/专家证词：勃林格勒。B. Campos Balea：发言人局/专家证词，差旅/住宿/费用：Roche；发言人局/专家证词：默克；发言人办公室/专家证词：百时美施贵宝（Bristol-Myers Squibb）；发言人小组/专家证词：阿斯利康；差旅/住宿/费用：礼来公司；咨询/顾问，旅行/住宿/费用：勃林格勒。N.Fernández-Núñez：发言人局/专家证词，差旅/住宿/费用：Roche；咨询/顾问，发言人局/专家证词，差旅/住宿/费用：百时美施贵宝；发言人小组/专家证词：阿斯利康；差旅/住宿/费用：礼来公司；旅行/住宿/费用：辉瑞；咨询/顾问，发言人局/专家证词，差旅/住宿/费用：拜耳；发言人局/专家证词：Janssen；咨询/顾问，发言人局/专家证词：Boehinrger；发言人办公室/专家证词，差旅/住宿/费用：赛诺菲。JL Firvida Perez：发言人办公室咨询/顾问/专家证词：阿斯利康；咨询/顾问，发言人办公室/专家证词：百时美施贵宝；咨询/顾问，发言人局/专家证词：诺华；咨询/顾问，发言人局/专家证词：辉瑞；咨询/顾问，发言人办公室/专家证词：皮埃尔·法布尔（Pierre Fabre）；咨询/顾问，发言人团/专家证词：武田；咨询/顾问，发言人局/专家证词：罗氏。J.GarcíaGonzález：咨询/顾问，发言人办公室/专家证词，差旅/住宿/费用：罗氏；咨询/顾问，旅行/住宿/费用：默克；咨询/顾问，旅行/住宿/费用：百时美施贵宝；咨询/顾问：阿斯利康；咨询/顾问：礼来公司；咨询/顾问：辉瑞；咨询/顾问，旅行/住宿/费用：勃林格勒。M.LázaroQuintela：咨询/顾问，发言人局/专家证词，差旅/住宿/费用：Roche；咨询/顾问，发言人局/专家证词，差旅/住宿/费用：默克；咨询/顾问：百时美施贵宝；发言人局/专家证词：阿斯利康 发言人办公室/专家证词，差旅/住宿/费用：礼来公司；旅行/住宿/费用：辉瑞；发言人局/专家证词：Janssen；咨询/顾问：GSK；咨询/顾问，发言人局/专家证词：Ipsen；咨询/顾问，发言人局/专家证词，差旅/住宿/费用：勃林格；咨询/顾问，差旅/住宿/费用：武田；咨询/顾问：赛诺菲；咨询/顾问：Tesaro。L.León-Mateos：发言人办公室咨询/顾问/专家证词：Roche；咨询/顾问，发言人局/专家证词：默克；咨询/顾问，发言人办公室/专家证词：百时美施贵宝；发言人小组/专家证词：阿斯利康；发言人局/专家证词：辉瑞公司；咨询/顾问，发言人办公室/专家证词：勃林格勒。J.Ruíz-Bañobre：咨询/顾问：勃林格；旅行/住宿/费用：百时美施贵宝；旅行/住宿/费用：默克；差旅/住宿/费用：IPSEN；旅行/住宿/费用：PharmaMar；发言人办公室/专家证词：罗氏（Roche）。D.PérezParente：全职/兼职：Roche。L. Crama：全职/兼职：Roche。P. Ruiz Gracia：全职/兼职：Roche。L.SantoméCouto：发言人办公室/专家证词，差旅/住宿/费用：Roche；咨询/顾问：百时美施贵宝；旅行/住宿/费用：辉瑞；咨询/顾问：勃林格勒。所有其他作者都声明没有利益冲突。旅行/住宿/费用：百时美施贵宝；旅行/住宿/费用：默克；差旅/住宿/费用：IPSEN；旅行/住宿/费用：PharmaMar；发言人办公室/专家证词：罗氏。D.PérezParente：全职/兼职：Roche。L. Crama：全职/兼职：Roche。P. Ruiz Gracia：全职/兼职：Roche。L.SantoméCouto：发言人办公室/专家证词，差旅/住宿/费用：Roche；咨询/顾问：百时美施贵宝；旅行/住宿/费用：辉瑞；咨询/顾问：勃林格勒。所有其他作者都声明没有利益冲突。旅行/住宿/费用：百时美施贵宝；旅行/住宿/费用：默克；差旅/住宿/费用：IPSEN；旅行/住宿/费用：PharmaMar；发言人办公室/专家证词：罗氏（Roche）。D.PérezParente：全职/兼职：Roche。L. Crama：全职/兼职：Roche。P. Ruiz Gracia：全职/兼职：Roche。L.SantoméCouto：发言人办公室/专家证词，差旅/住宿/费用：Roche；咨询/顾问：百时美施贵宝；旅行/住宿/费用：辉瑞；咨询/顾问：勃林格勒。所有其他作者都声明没有利益冲突。发言人办公室/专家证词：罗氏。D.PérezParente：全职/兼职：Roche。L. Crama：全职/兼职：Roche。P. Ruiz Gracia：全职/兼职：Roche。L.SantoméCouto：发言人办公室/专家证词，差旅/住宿/费用：Roche；咨询/顾问：百时美施贵宝；旅行/住宿/费用：辉瑞；咨询/顾问：勃林格勒。所有其他作者都声明没有利益冲突。发言人办公室/专家证词：罗氏（Roche）。D.PérezParente：全职/兼职：Roche。L. Crama：全职/兼职：Roche。P. Ruiz Gracia：全职/兼职：Roche。L.SantoméCouto：发言人办公室/专家证词，差旅/住宿/费用：Roche；咨询/顾问：百时美施贵宝；旅行/住宿/费用：辉瑞；咨询/顾问：勃林格勒。所有其他作者都声明没有利益冲突。布林格。所有其他作者都声明没有利益冲突。布林格。所有其他作者都声明没有利益冲突。