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Abstract：
BACKGROUND: Whether programmed cell death-1/ligand-1 (PD-1/PD-L1) blockade-based neoadjuvant treatment may benefit locally advanced oncogene-mutant non-small cell lung cancer (NSCLC) patients remains controversial. This retrospective study was designed to observe the efficacy and safety of neoadjuvant PD-1/PD-L1 blockade plus chemotherapy versus chemotherapy and corresponding tyrosine kinase inhibitors (TKIs) in patients with resectable oncogene-positive NSCLC.
METHODS: Patients with potential resectable NSCLC harbouring oncogene alterations who had received neoadjuvant treatment were retrospectively recruited, and an oncogene-negative cohort of patients who received neoadjuvant PD-(L)1 blockade-based neoadjuvant treatment was reviewed for comparison during the same period. The primary aim was to observe the treatment efficacy and event-free survival (EFS) of these agents. Safety profile, molecular target, and immunologic factor data, including PD-L1 expression and tumour mutational burden (TMB), were also obtained.
RESULTS: A total of 46 patients were recruited. Thirty-one of them harboured oncogene alterations, including EGFR, KRAS, ERBB2, ROS1, MET, RET, ALK, and FGFR3 alterations. Among the oncogene-positive patients, 18 patients received neoadjuvant PD-(L)1 blockade immunotherapy plus chemotherapy (oncogene-positive IO group), 13 patients were treated with neoadjuvant chemotherapy and/or corresponding TKIs or TKIs alone (oncogene-positive chemo/TKIs group), and the other 15 patients were oncogene negative and received neoadjuvant PD-(L)1 blockade plus chemotherapy (oncogene-negative IO group). The pathological complete response (pCR) and major pathological response (MPR) rates were 22.2% (4 of 18) and 44.4% (8 of 18) in the oncogene-positive IO group, 0% (P = 0.120) and 23.1% (3 of 13) (P = 0.276) in the oncogene-positive chemo/TKIs group, and 46.7% (7 of 15) (P = 0.163) and 80.0% (12 of 15) (P = 0.072) in the oncogene-negative IO group, respectively. By the last follow-up, the median EFS time had not reached in the oncogene-positive IO group, and was 29.5 months in the oncogene-positive chemo/TKIs group and 38.4 months in the oncogene-negative IO group.
CONCLUSIONS: Compared with chemotherapy/TKIs treatment, neoadjuvant treatment with PD-(L)1 blockade plus platinum-based chemotherapy was associated with higher pCR/MPR rates in patients with partially resectable oncogene-mutant NSCLC, while the pCR/MPR rates were lower than their oncogene-negative counterparts treated with PD-(L)1 blockade-based treatment. Specifically, oncogene alteration types and other predictors of response to immunotherapy should be taken into account in clinical practice.
METHODS: Patients with potential resectable NSCLC harbouring oncogene alterations who had received neoadjuvant treatment were retrospectively recruited, and an oncogene-negative cohort of patients who received neoadjuvant PD-(L)1 blockade-based neoadjuvant treatment was reviewed for comparison during the same period. The primary aim was to observe the treatment efficacy and event-free survival (EFS) of these agents. Safety profile, molecular target, and immunologic factor data, including PD-L1 expression and tumour mutational burden (TMB), were also obtained.
RESULTS: A total of 46 patients were recruited. Thirty-one of them harboured oncogene alterations, including EGFR, KRAS, ERBB2, ROS1, MET, RET, ALK, and FGFR3 alterations. Among the oncogene-positive patients, 18 patients received neoadjuvant PD-(L)1 blockade immunotherapy plus chemotherapy (oncogene-positive IO group), 13 patients were treated with neoadjuvant chemotherapy and/or corresponding TKIs or TKIs alone (oncogene-positive chemo/TKIs group), and the other 15 patients were oncogene negative and received neoadjuvant PD-(L)1 blockade plus chemotherapy (oncogene-negative IO group). The pathological complete response (pCR) and major pathological response (MPR) rates were 22.2% (4 of 18) and 44.4% (8 of 18) in the oncogene-positive IO group, 0% (P = 0.120) and 23.1% (3 of 13) (P = 0.276) in the oncogene-positive chemo/TKIs group, and 46.7% (7 of 15) (P = 0.163) and 80.0% (12 of 15) (P = 0.072) in the oncogene-negative IO group, respectively. By the last follow-up, the median EFS time had not reached in the oncogene-positive IO group, and was 29.5 months in the oncogene-positive chemo/TKIs group and 38.4 months in the oncogene-negative IO group.
CONCLUSIONS: Compared with chemotherapy/TKIs treatment, neoadjuvant treatment with PD-(L)1 blockade plus platinum-based chemotherapy was associated with higher pCR/MPR rates in patients with partially resectable oncogene-mutant NSCLC, while the pCR/MPR rates were lower than their oncogene-negative counterparts treated with PD-(L)1 blockade-based treatment. Specifically, oncogene alteration types and other predictors of response to immunotherapy should be taken into account in clinical practice.
摘要：
背景：基于程序性细胞死亡-1/配体-1（PD-1/PD-L1）阻断的新辅助治疗是否可以使局部晚期癌基因突变的非小细胞肺癌（NSCLC）患者受益仍存在争议。这项回顾性研究旨在观察新辅助PD-1/PD-L1阻断联合化疗与化疗和相应的酪氨酸激酶抑制剂（TKIs）对可切除癌基因阳性NSCLC患者的疗效和安全性。
方法：回顾性招募接受新辅助治疗的有癌基因改变的潜在可切除NSCLC患者，在同一时期内,我们对接受新辅助PD-(L)1阻断型新辅助治疗的癌基因阴性患者队列进行了回顾比较.主要目的是观察这些药物的疗效和无事件生存期（EFS）。安全概况,分子靶标,和免疫因素数据，包括PD-L1表达和肿瘤突变负担（TMB），也得到了。
结果：共纳入46例患者。其中31个有癌基因改变，包括EGFR,KRAS,ERBB2,ROS1,MET,RET,ALK,和FGFR3改变。在癌基因阳性的患者中，18例患者接受新辅助PD-（L）1阻断免疫疗法加化疗（癌基因阳性IO组），13例患者接受新辅助化疗和/或相应的TKIs或TKIs单独治疗（癌基因阳性化疗/TKIs组），其他15例患者为癌基因阴性，接受新辅助PD-（L）1阻断加化疗（癌基因阴性IO组）。癌基因阳性IO组病理完全缓解(pCR)和主要病理缓解(MPR)率分别为22.2%(18个中的4个)和44.4%(18个中的8个),0％（P=0.120）和23.1％（13个中的3个）（P=0.276）在癌基因阳性化疗/TKIs组，癌基因阴性IO组的46.7%(15个中的7个)(P=0.163)和80.0%(15个中的12个)(P=0.072)，分别。在最后的后续行动中，癌基因阳性IO组的中位EFS时间未达到，癌基因阳性化疗/TKIs组为29.5个月，癌基因阴性IO组为38.4个月。
结论：与化疗/TKIs治疗相比，PD-(L)1阻断联合铂类化疗的新辅助治疗在部分可切除癌基因突变NSCLC患者中与较高的pCR/MPR率相关。而pCR/MPR率低于以PD-（L）1阻断为基础的治疗方案的癌基因阴性者。具体来说,在临床实践中,应考虑癌基因改变类型和免疫治疗反应的其他预测因子.
方法：回顾性招募接受新辅助治疗的有癌基因改变的潜在可切除NSCLC患者，在同一时期内,我们对接受新辅助PD-(L)1阻断型新辅助治疗的癌基因阴性患者队列进行了回顾比较.主要目的是观察这些药物的疗效和无事件生存期（EFS）。安全概况,分子靶标,和免疫因素数据，包括PD-L1表达和肿瘤突变负担（TMB），也得到了。
结果：共纳入46例患者。其中31个有癌基因改变，包括EGFR,KRAS,ERBB2,ROS1,MET,RET,ALK,和FGFR3改变。在癌基因阳性的患者中，18例患者接受新辅助PD-（L）1阻断免疫疗法加化疗（癌基因阳性IO组），13例患者接受新辅助化疗和/或相应的TKIs或TKIs单独治疗（癌基因阳性化疗/TKIs组），其他15例患者为癌基因阴性，接受新辅助PD-（L）1阻断加化疗（癌基因阴性IO组）。癌基因阳性IO组病理完全缓解(pCR)和主要病理缓解(MPR)率分别为22.2%(18个中的4个)和44.4%(18个中的8个),0％（P=0.120）和23.1％（13个中的3个）（P=0.276）在癌基因阳性化疗/TKIs组，癌基因阴性IO组的46.7%(15个中的7个)(P=0.163)和80.0%(15个中的12个)(P=0.072)，分别。在最后的后续行动中，癌基因阳性IO组的中位EFS时间未达到，癌基因阳性化疗/TKIs组为29.5个月，癌基因阴性IO组为38.4个月。
结论：与化疗/TKIs治疗相比，PD-(L)1阻断联合铂类化疗的新辅助治疗在部分可切除癌基因突变NSCLC患者中与较高的pCR/MPR率相关。而pCR/MPR率低于以PD-（L）1阻断为基础的治疗方案的癌基因阴性者。具体来说,在临床实践中,应考虑癌基因改变类型和免疫治疗反应的其他预测因子.
