Abstract

Background

We often experience long-lasting response of PD-1 inhibitor in advanced NSCLC patients. However, the characteristics associated with long-lasting response to PD-1 inhibitor is still unknown. In this study, we investigated the characteristics of patients who showed long-lasting (≥2 years) response to anti-PD-1 antibodies.

Methods

We reviewed consecutive advanced NSCLC patients who received a PD-1 inhibitor monotherapy (nivolumab, or pembrolizumab) between December 22, 2015 and May 31, 2017 at National Cancer Center Hospital in Japan. The cut-off date was June 1, 2019. We defined patients who obtained clinical benefit for more than 6 months as “Responders”. Among them, those who had a durable response for more than 2 years were defined as “Long-term responders” (LTR), and those who responded or shorter than 2 years as “Non-LTR”. We investigated the patient baseline characteristics and clinical outcomes of anti-PD-1 monotherapy including objective response rate (ORR) and maximal tumor shrinkage. Tumor response was assessed by RECIST version 1.1. The PD-L1 expression on tumor cells was assessed by using 22C3 antibody.

Results

A total of 232 patients were included in this analysis. Responders accounted for 37.9 % (88 out of 232). Of these patients, 31 (35.2%) were LTR group and 57 (64.8 %) were non-LTR group. At the time of data cut off, 22 (71.0%) of 31 patients in LTR group showed lasting response of PD-1 inhibitor. There were no significant differences in the baseline characteristics such as age, sex, performance status, driver mutation, clinical stage, and smoking status. Regarding histological distribution, non-squamous cell histology was more common in the LTR group (68% vs. 90%, P = 0.021). The ORR in the LTR group was significantly higher than non-LTR group (80.6% vs. 32.0%, P <0.0001). The median tumor shrinkage (range) in the LTR group was also significantly higher than that in the non-LTR group [72.8 (range: 6.8-100)% vs 48.7(range: 3.9-100)% (P=0.0002)]. In contrast, no difference was found in the PD-L1 expression between two groups (P = 0.213).

Conclusion

Long-lasting response of PD-1 inhibitor was particularly characterized by high tumor shrinkage in patients who had response to PD-1 inhibitors.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

Y. Okuma: Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Chugai. Y. Goto: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony, Research grant / Funding (institution): ONO; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Shionogi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Glaxo Smith Kline; Advisory / Consultancy: Guardant Hearlth; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Dai-ichi Sankyo; Research grant / Funding (institution): Kyorin. H. Horinouchi: Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZaneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho; Speaker Bureau / Expert testimony, Research grant / Funding (institution): ONO; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol Myers Squibb; Speaker Bureau / Expert testimony: Kyowa-kirin; Research grant / Funding (institution): Abbvie; Speaker Bureau / Expert testimony: Dai-ichi Sankyo; Research grant / Funding (institution): Kyorin; Research grant / Funding (institution): Genomic Health. N. Yamamoto: Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy: Otsuka; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy: Cimic; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Eli Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (institution): ONO; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Chugai; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Daiichi-Sankyo; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Kyowa-Hakko Kirin; Research grant / Funding (institution): JansenPharma; Research grant / Funding (institution): MSD. Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): ONO; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristrol-Myers Squibb; Honoraria (self): Boehringer lngelheim; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): Taiho; Advisory / Consultancy, Research grant / Funding (institution): Kyorin; Advisory / Consultancy: Celltrion; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Dainippon Sumitomo; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ignyta; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Kissei; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Daiichi-Sankyo. All other authors have declared no conflicts of interest.

中文翻译：

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77P晚期非小细胞肺癌患者对PD-1抑制剂的长期应答特性

抽象的

背景

我们经常在晚期NSCLC患者中经历PD-1抑制剂的长期应答。然而，与对PD-1抑制剂的持久应答有关的特性仍是未知的。在这项研究中，我们调查了对抗PD-1抗体表现出长期（≥2年）反应的患者的特征。

方法

我们回顾了2015年12月22日至2017年5月31日之间在日本国家癌症中心医院接受PD-1抑制剂单药治疗（nivolumab或pembrolizumab）的连续晚期NSCLC患者。截止日期为2019年6月1日。我们将获得临床获益6个月以上的患者定义为“响应者”。其中，将持续响应时间超过2年的人定义为“长期响应者”（LTR），将响应时间小于或等于2年的人定义为“非响应者”。我们调查了抗PD-1单药治疗的患者基线特征和临床结局，包括客观缓解率（ORR）和最大肿瘤缩小。RECIST 1.1版评估了肿瘤反应。通过使用22C3抗体评估肿瘤细胞上PD-L1的表达。

结果

该分析总共包括232名患者。回应者占37.9％（232人中占88位）。在这些患者中，LTR组31例（35.2％），非LTR组57例（64.8％）。在数据截止时，LTR组的31例患者中有22例（71.0％）表现出PD-1抑制剂的持久应答。基线特征（例如年龄，性别，工作状态，驾驶员突变，临床阶段和吸烟状态）没有显着差异。就组织学分布而言，LTR组中非鳞状细胞组织学更为常见（68％比90％，P = 0.021）。LTR组的ORR显着高于非LTR组（80.6％对32.0％，P <0.0001）。LTR组的中位肿瘤缩小率（范围）也显着高于非LTR组[72.8（范围：6.8-100）％对48.7（范围：3.9-100）％（P = 0.0002）]。

结论

PD-1抑制剂的持久应答特别以对PD-1抑制剂有应答的患者的高肿瘤缩小为特征。

负责研究的法人实体

作者。

资金

尚未收到任何资金。

揭露

Y. Okuma：研究资助/资助（机构）：武田；研究补助金/经费（机构）：中外。Y. Goto：咨询/顾问，发言人局/专家证词：AstraZeneca；咨询/顾问，发言人局/专家证词，研究资助/资助（机构）：礼来公司；咨询/顾问，发言人局/专家证词：中外；咨询/顾问，发言人局/专家证词，研究资助/资助（机构）：Taiho；咨询/顾问，发言人办公室/专家证词：勃林格殷格翰公司；发言人局/专家证词，研究资助/资助（机构）：ONO；发言人局/专家证词，研究资助/资助（机构）：Bristol Myers Squibb；咨询/顾问，发言人局/专家证词，研究资助/资助（机构）：辉瑞；咨询/顾问，发言人局/专家证词：MSD；发言人局/专家证词：盐野木；咨询/顾问，发言人局/专家证词，研究资助/资助（机构）：诺华；咨询/顾问：葛兰素史克（Glaxo Smith Kline）；咨询/顾问：Guardant Hearlth；研究资助/资助（机构）：Abbvie；研究资助/经费（机构）：第一三共；研究补助金/经费（机构）：Kyorin。H. Horinouchi：发言人办公室咨询/顾问/专家证词：礼来公司；咨询/顾问，发言人局/专家证词，研究资助/资助（机构）：中外；咨询/顾问：勃林格殷格翰公司；咨询/顾问，发言人局/专家证词，研究资助/资助（机构）：诺华；咨询/顾问，发言人局/专家证词：AstraZaneca；咨询/顾问，发言人局/专家证词，研究资助/资助（机构）：MSD；发言人局/专家证词，研究资助/资助（机构）：Taiho；发言人局/专家证词，研究资助/资助（机构）：ONO；发言人局/专家证词，研究资助/资助（机构）：Bristol Myers Squibb；发言人局/专家证词：协和麒麟；研究补助金/资金（机构）：Abbvie；发言人办公室/专家证词：第一三共；研究经费/资助（机构）：Kyorin；研究资助/资助（机构）：基因组健康。N. Yamamoto：咨询/顾问，研究补助金/经费（机构）：Eisai；咨询/顾问，研究资助/资助（机构）：武田；咨询/顾问：大冢；咨询/顾问，研究资助/资助（机构）：勃林格殷格翰；咨询/顾问：Cimic；发言人局/专家证词，研究资助/资助（机构）：Bristol-Myers Squibb；发言人办公室/专家证词，研究资助/资助（机构）：辉瑞；发言人小组/专家证词：阿斯利康；发言人局/专家证词，研究资助/资助（机构）：礼来公司；发言人局/专家证词，研究资助/资助（机构）：ONO；发言人局/专家证词，研究资助/资助（机构）：中外；研究补助金/经费（机构）：Astellas；研究补助金/资金（机构）：Taiho；研究经费/资助（机构）：诺华；研究补助金/资金（机构）：Abbvie；研究补助金/经费（机构）：第一三共；研究资助/资助（机构）：拜耳；研究补助金/经费（机构）：Kyowa-Hakko Kirin；研究经费/资助（机构）：JansenPharma；研究经费/资助（机构）：MSD。Y. Ohe：Honoraria（个体经营），咨询/顾问，研究补助金/资金（机构）：AstraZeneca；酬金（个体经营），咨询/顾问，研究经费/资助（机构）：中外；酬金（自己），研究资助/资助（机构）：礼来；酬金（个体经营），咨询/顾问，研究经费/资助（机构）：ONO；酬金（个体经营），咨询/顾问，研究经费/资助（机构）：Bristrol-Myers Squibb；Honoraria（个体）：勃林格殷格翰（Boehringer lngelheim）; Honoraria（个体）：拜耳; 酬金（自己），研究资助/资助（机构）：辉瑞；Honoraria（个体）：MSD; Honoraria（个体经营），研究补助金/资金（机构）：Taiho；咨询/顾问，研究资助/资助（机构）：Kyorin；咨询/顾问：Celltrion；研究补助金/资金（机构）：Amgen；研究资助/经费（机构）：Dainippon Sumitomo; 研究经费/资助（机构）：诺华；研究补助金/资金（机构）：Ignyta；研究补助金/经费（机构）：武田；研究经费/资助（机构）：Kissei; 研究补助金/资金（机构）：Janssen；研究补助金/经费（机构）：第一三共。所有其他作者都声明没有利益冲突。研究经费/资助（机构）：诺华；研究补助金/资金（机构）：Ignyta；研究补助金/经费（机构）：武田；研究经费/资助（机构）：Kissei; 研究补助金/资金（机构）：Janssen；研究补助金/经费（机构）：第一三共。所有其他作者都声明没有利益冲突。研究经费/资助（机构）：诺华；研究补助金/资金（机构）：Ignyta；研究补助金/经费（机构）：武田；研究经费/资助（机构）：Kissei; 研究补助金/资金（机构）：Janssen；研究补助金/经费（机构）：第一三共。所有其他作者都声明没有利益冲突。