2025年12月26日肺癌大事件将在井冈山拉开帷幕，广东省人民医院吴一龙教授将对2025年肺癌治疗领域的重要研究进展进行了深入的盘点和解读。由此吴一龙教授提问，你心目中2025年中国肺癌的10篇文章是哪些？并邀请所有同道医生参与调研，希望从13项重要候选研究中，由您投票选出心目中最具影响力的10项，并从“改变实践”、“推动获批”、“概念创新”几个维度进行评价。您的意见非常重要，诚邀您用5分钟时间，点击问卷调研开始投票。
研究一
芦康沙妥珠单抗用于EGFR-TKI耐药、EGFR突变的晚期非小细胞肺癌
Overall, 376 patients underwent randomization, with 188 assigned to each group. After a median follow-up of 18.9 months, the median progression-free survival was 8.3 months in the sac-TMT group and 4.3 months in the chemotherapy group (hazard ratio for disease progression or death, 0.49; 95% confidence interval [CI], 0.39 to 0.62).
Overall survival was significantly longer with sac-TMT than with chemotherapy (hazard ratio for death, 0.60; 95% CI, 0.44 to 0.82; two-sided P = 0.001); 18-month overall survival was 65.8% and 48.0%, respectively.
Treatment-related adverse events of grade 3 or higher occurred in 58.0% of patients receiving sac-TMT and in 53.8% of those receiving chemotherapy, with the most common being a decreased neutrophil count (39.9% vs. 33.0%); treatment-related serious adverse events occurred in 9.0% and 17.6%, respectively.
研究二
依沃西单抗联合化疗对比替雷利珠单抗联合化疗作为晚期鳞状非小细胞肺癌的一线治疗（HARMONi-6）：一项随机、双盲、III期试验
From Aug 17, 2023, to Jan 21, 2025, 761 patients were screened for eligibility, among whom 532 (70%) patients were enrolled and randomly assigned to receive ivonescimab plus chemotherapy (266 [50%] patients) or tislelizumab plus chemotherapy (266 [50%] patients).
As of Feb 28, 2025, median follow-up time was 10·3 months (95% CI 9.5–11.0). Median progression-free survival was 11·1 months (95% CI 9.9–not evaluable) in the ivonescimab group and 6.9 months (5.8–8.6) in the tislelizumab group (hazard ratio 0·60 [95% CI 0·46–0·78]; one-sided p<0·0001). The progression-free survival benefit with ivonescimab plus chemotherapy was consistent regardless of PD-L1 status.
170 (64%) patients in the ivonescimab group and 144 (54%) patients in the tislelizumab group had grade 3 or higher treatment-related adverse events, with grade 3 or higher immune-related adverse events occurring in 24 (9%) patients in the ivonescimab group and in 27 (10%) patients in the tislelizumab group. Grade 3 or higher treatment-related haemorrhage occurred in five (2%) patients in the ivonescimab group and in two (1%) patients in the tislelizumab group.
研究三
依沃西单抗对比帕博利珠单抗用于PD-L1阳性非小细胞肺癌（HARMONi-2）：一项在中国开展的随机、双盲、III期研究
Between Nov 9, 2022, and Aug 26, 2023, 398 (45%) of 879 screened patients were randomly assigned to receive ivonescimab (n=198) or pembrolizumab (n=200).
At the preplanned interim analysis, median PFS was significantly longer with ivonescimab than with pembrolizumab (11·1 vs 5·8 months; stratified hazard ratio [HR] 0·51 [95% CI 0·38–0·69]; one-sided p<0·0001). The PFS benefit of ivonescimab over pembrolizumab was broadly consistent within prespecified subgroups, including patients with PD-L1 tumour proportion score (TPS) 1–49% (HR 0·54 [95% CI 0·37–0·78]) and PD-L1 TPS of 50% of higher (HR 0·48 [0·29–0·79]).
Grade 3 or higher treatment-related adverse events occurred in 58 (29%) patients with ivonescimab and 31 (16%) patients with pembrolizumab. Immune-related adverse events of grade 3 or higher were observed in 14 (7%) of 197 patients on ivonescimab and 16 (8%) of 199 patients on pembrolizumab. Ivonescimab demonstrated a manageable safety profile in patients with both squamous and non-squamous non-small cell lung cancer. In patients with squamous cell carcinoma, grade 3 or higher treatment-related adverse events were comparable between the two groups.
研究四
伯瑞替尼用于MET扩增驱动的晚期非小细胞肺癌（KUNPENG）：一项单臂、多队列、II期研究
Between Jan 17, 2020, and Nov 14, 2023, 145 patients were enrolled; of these, 86 patients (30 chemotherapy-treated and 56 untreated) from cohorts 2 and 3 were included in the current analysis. The median age was 65 years (range 48–82; IQR 59–71), 77 (90%) patients were male, and nine (10%) were female. All patients were Chinese.
42 patients had partial response, resulting in an objective response rate of 48·8% (42 of 86; 95% CI 38·3–59·4) per masked independent review committee. The median follow-up was 18·6 months (IQR 15·7–37·3).
The incidence of grade 3 or worse treatment-related adverse events was 31% (27 of 86), predominantly abnormal liver function terms reported by the investigators (eight [9%]). Serious adverse events related to treatment were reported by 16 (19%) patients. 11 treatment-emergent adverse events leading to death occurred, of which one patient died of abnormal liver function, which was possibly related to vebreltinib treatment.
研究五
芦康沙妥珠单抗对比多西他赛用于既往经治的EGFR突变晚期非小细胞肺癌：多中心、开放标签、随机对照试验
137 patients were randomised to receive sac-TMT (n=91) or docetaxel (n=46). Median follow-up was 12.2 months at the data cut-off for efficacy (31 December 2024).
BIRC assessed objective response rate was significantly higher in the sac-TMT group (45% (41/91)) v docetaxel (16% (7/45)), with a difference of 29% (95% confidence interval (CI) 15% to 43%; one sided P<0.001). Median progression-free survival was longer with sac-TMT than with docetaxel assessed by BIRC (6.9 v 2.8 months; hazard ratio 0.30, 95% CI 0.20 to 0.46; one sided P<0.001) and the investigator (7.9 v 2.8 months; hazard ratio 0.23, 0.15 to 0.36; one sided P<0.001). The 12 month overall survival rate was 73% with sac-TMT and 54% with docetaxel (hazard ratio 0.49, 0.27 to 0.88; one sided P=0.007). After adjustment for crossover using the rank-preserving structural failure time model, sac-TMT also showed improved overall survival (hazard ratio 0.36, 0.20 to 0.66).
Grade ≥3 treatment related adverse events were less frequent with sac-TMT than with docetaxel (56% v 72%), with no new safety signals identified.
研究六
替雷利珠单抗联合新辅助化疗用于可切除非小细胞肺癌患者围手术期的治疗（RATIONALE-315）：一项随机临床试验的中期分析
Between June 8, 2020, and Aug 31, 2022, 453 patients were assigned to tislelizumab (n=226) or placebo (n=227). The median age of patients was 62·0 years (IQR 56·0–67·0). 410 (91%) of 453 patients were male and 43 (9%) were female. As of Aug 21, 2023 (data cutoff for the interim analysis of event-free survival), median duration of follow-up was 22·0 months (IQR 15·5–28·0).
Tislelizumab significantly improved event-free survival versus placebo (stratified hazard ratio 0·56 [95% CI 0·40–0·79]; one-sided p=0·0003). The major pathological response rate was significantly higher in the tislelizumab group (56% [95% CI 50–63]) than in the placebo group (15% [11–20]; difference 41% [33–49]; one-sided p<0·0001).
Grade 3 or worse adverse events and serious treatment-related adverse events occurred in 163 (72%) of 226 patients and 35 (15%) of 226 patients, respectively, in the tislelizumab group, and in 150 (66%) and 18 (8%) patients, respectively, in the placebo group. The most common grade 3 or worse treatment-related adverse event was decreased neutrophil count (138 [61%] of 226 in the tislelizumab group vs 134 [59%] of 226 in the placebo group). 31 (14%) of 226 patients in the tislelizumab group and 45 (20%) of 227 patients in the placebo group died during the study.
研究七
戈来雷塞用于KRAS G12C突变非小细胞肺癌：一项IIb期试验
Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRAS G12C-mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC).
Between 15 September 2022 and 28 September 2023, 119 patients with a median age of 62 years were enrolled. As of the data cut-off date on 28 March 2024, the ORR assessed by IRC was 47.9% (56/117; 95% confidence interval: 38.5–57.3%).
The incidence of treatment-related adverse events (TRAEs) of any grade was 97.5% (116/119). The incidence of grades 3 and 4 TRAEs was 38.7% (46/119). A total of 5.0% (6/119) of patients discontinued the treatment due to TRAEs. No treatment-related deaths occurred. Glecirasib exhibited promising clinical efficacy and manageable safety profiles in these patient populations.
研究八
芦康沙妥珠单抗联合Tagitanlimab作为晚期非小细胞肺癌的一线治疗：一项II期试验
Sacituzumab tirumotecan (sac-TMT, also known as MK-2870 or SKB264) is an antibody–drug conjugate targeting trophoblast cell surface antigen 2. We report the initial findings from the ongoing phase 2 OptiTROP-Lung01 study, evaluating the combination of sac-TMT and tagitanlimab (KL-A167), an anti-PD-L1 antibody, as first-line therapy in patients with advanced or metastatic non-small-cell lung cancer who lack actionable genomic alterations (cohorts 1A and 1B).
Cohort 1A received sac-TMT (5 mg kg−1,every 3 weeks) plus tagitanlimab (1,200 mg, every 3 weeks) in each 3-week cycle, whereas cohort 1B was treated with sac-TMT (5 mg kg−1,every 2 weeks) plus tagitanlimab (900 mg, every 2 weeks) in each 4-week cycle, in a nonrandomized manner until disease progression or unacceptable toxicity. The primary endpoints included safety and objective response rate. This study was not powered for formal hypothesis testing.A total of 40 and 63 patients were enrolled in cohorts 1A and 1B, respectively. The median age was 63 years in both cohorts. An Eastern Cooperative Oncology Group performance status of 1 was observed in 97.5% and 85.7% of patients in cohorts 1A and 1B, respectively.
In cohorts 1A and 1B, the most common grade ≥3 treatment-related adverse events were decreased neutrophil count (30.0% and 34.9%), decreased white blood cell count (5.0% and 19.0%) and anemia (5.0% and 19.0%). No treatment-related deaths were observed.
After median follow-ups of 19.3 months for cohort 1A and 13.0 months for cohort 1B, the confirmed objective response rate in the full analysis set was 40.0% (16 of 40) and 66.7% (42 of 63), the disease control rate was 85.0% and 92.1% and median progression-free survival was 15.4 months (95% confidence interval 6.7–17.9) and not reached for cohorts 1A and 1B, respectively. sac-TMT plus tagitanlimab showed promising efficacy as a first-line treatment for advanced or metastatic non-small-cell lung cancer, with a manageable safety profile.
研究九
瑞康曲妥珠单抗，一种靶向HER2的抗体偶联药物，用于晚期HER2突变非小细胞肺癌患者（HORIZON-Lung）：一项多中心、单臂II期研究结果
Between April 14, 2023, and Dec 14, 2023, 94 patients were enrolled and treated. 42 (45%) patients were male, 52 (55%) female, 92 (98%) were Han Chinese, and two (2%) were other ethnicity Chinese.
At data cutoff (June 14, 2024), the median duration of follow-up was 8·7 months (IQR 7·0–10·4). 69 (73%; 95% CI 63·3–82·0) of 94 patients had a confirmed objective response, as assessed by independent review committee.
The most common grade 3–4 treatment-related adverse events were decreased neutrophil count (38 [40%] patients), decreased white blood cell count (25 [27%]), anaemia (22 [23%]), decreased platelet count (10 [11%]), and decreased lymphocyte count (seven [7%]).Treatment-related serious adverse events occurred in 22 (23%) patients, which were decreased platelet count (six [6%]), decreased neutrophil count (six [6%]), interstitial lung disease (five [5%]), decreased white blood cell count (four [4%]), anaemia (four [4%]), vomiting (three [3%]), pneumonia (three [3%]), hyponatraemia (two [2%]), and pyrexia (one [1%]), small intestinal obstruction (one [1%]), nausea (one [1%]), and chronic obstructive pulmonary disease (one [1%]). There were no treatment-related deaths.
研究十
特瑞普利单抗联合化疗作为广泛期小细胞肺癌的一线治疗：III期EXTENTORCH随机临床试验
Between June 8, 2020, and Aug 31, 2022, 453 patients were assigned to tislelizumab (n=226) or placebo (n=227). The median age of patients was 62·0 years (IQR 56·0–67·0). 410 (91%) of 453 patients were male and 43 (9%) were female.
As of Aug 21, 2023 (data cutoff for the interim analysis of event-free survival), median duration of follow-up was 22·0 months (IQR 15·5–28·0). Tislelizumab significantly improved event-free survival versus placebo (stratified hazard ratio 0·56 [95% CI 0·40–0·79]; one-sided p=0·0003). The major pathological response rate was significantly higher in the tislelizumab group (56% [95% CI 50–63]) than in the placebo group (15% [11–20]; difference 41% [33–49]; one-sided p<0·0001).
Grade 3 or worse adverse events and serious treatment-related adverse events occurred in 163 (72%) of 226 patients and 35 (15%) of 226 patients, respectively, in the tislelizumab group, and in 150 (66%) and 18 (8%) patients, respectively, in the placebo group. The most common grade 3 or worse treatment-related adverse event was decreased neutrophil count (138 [61%] of 226 in the tislelizumab group vs 134 [59%] of 226 in the placebo group). 31 (14%) of 226 patients in the tislelizumab group and 45 (20%) of 227 patients in the placebo group died during the study.
研究十一
NSCLC软脑膜转移的演变格局：一项国际、当代、多中心队列研究
A total of 2052 patients with NSCLC and LMD were included and analyzed by molecular subtypes: epidermal growth factor receptor (EGFR) (n =1610), ALK (n =141), other actionable genomic alterations (other AGA; n =137), and non-AGA (n =164). The cumulative prevalence of LMD by molecular subgroups was EGFR, 11.1%; ALK, 11.2%; ROS1, 16%; ERBB2, 12.3%, non-AGA, 3.6%. A higher proportion of LMD was diagnosed >3 years after initial metastatic diagnosis. By the European Association of Neuro-Oncology (EANO)—European Society for Medical Oncology (ESMO) diagnostic criteria, type I (cerebrospinal fluid cytology positive) had significantly shorter LMOS than type II (magnetic resonance imaging and/or symptom positive).
Median LMOS was 10.9 months [95% confidence interval (CI) 10.0-11.8 months] in all patients. Compared with historical cohorts, patients demonstrated improved LMOS in contemporary cohorts (7.3 versus 11.5 months, P <0.0001), across all molecular subtypes. In AGA NSCLC, tyrosine kinase inhibitors (TKIs) were associated with improved LMOS [hazard ratio (HR) 0.39, 95% CI 0.31-0.48, P <0.0001]. Immune checkpoint inhibitors (ICIs) conferred survival benefit in non-AGA patients (HR 0.45, 95% CI 0.25-0.84, P =0.012). For the EGFR-mutated cohort, central nervous system (CNS)-penetrant TKI usage delayed LMD onset (P <0.0001). Continued CNS-penetrant TKIs after LMD diagnosis were associated with longer LMOS (12.4 versus 6.0 months, P <0.0001).
研究十二
脑放疗联合卡瑞利珠单抗和铂类双药化疗用于初治的、伴脑转移晚期非小细胞肺癌（C-Brain）：一项多中心、单臂、II期试验
Between May 6, 2020, and Jan 30, 2023, 67 patients were assessed for eligibility. Two patients were excluded (brain lesions less than 5 mm) and 65 patients were enrolled and treated. Median age was 66 years (IQR 62-70). 60 (92%) of 65 patients were male and five (8%) were female. All 65 patients were Han Chinese. 50 (77%) of 65 patients had non-squamous NSCLC and 46 (71%) were symptomatic.
The 6-month progression-free survival rate was 71·7% (95% CI 58·9-81·1) during the median follow-up of 14·1 months (IQR 9·0-20·3; data cutoff Dec 13, 2023).
The most common grade 3-4 treatment-related adverse events were decreased neutrophil count (14 [22%] of 65 patients), decreased white blood cell count (ten [15%]), decreased platelet count (ten [15%]), and decreased lymphocyte count (nine [14%]). Neurological toxic effects of grade 3 occurred in three (5%) of 65 patients. Radiation necrosis occurred in three (5%) of 65 patients; all were grade 1 or 2. There were no treatment-related deaths.
研究十三
阿替利珠单抗联合贝伐珠单抗和化疗治疗转移性非鳞状NSCLC：随机双盲III期IMpower151试验
Chemotherapy-naïve patients with metastatic nsqNSCLC (N = 305) were randomized 1:1 to receive either atezolizumab, bevacizumab, carboplatin and paclitaxel or pemetrexed (ABCPem/Pac; n = 152) or placebo plus bevacizumab, carboplatin and pemetrexed or paclitaxel (BCPem/Pac; n = 153). Most patients (97%) received pemetrexed, and 53% had EGFR+ tumors.
Median INV-PFS for ABCPem/Pac versus BCPem/Pac was 9.5 versus 7.1 months (stratified hazard ratio: 0.84; 95% confidence interval: 0.65, 1.09; P = 0.184).INV-PFS across subgroups and independent review facility-assessed PFS were consistent with INV-PFS in the intention-to-treat population. Median overall survival was 20.7 versus 18.7 months in the ABCPem/Pac versus BCPem/Pac arms, respectively (stratified hazard ratio: 0.93; 95% confidence interval: 0.67, 1.28). Confirmed objective response rate with ABCPem/Pac versus BCPem/Pac was 48% versus 50%, respectively; median duration of response was 11.3 versus 8.3 months.
Adverse events of special interest for atezolizumab were observed in 68% (grades 3 and 4: 11%) and 71% (grades 3 and 4: 7%) of patients receiving ABCPem/Pac and BCPem/Pac, respectively. The most common adverse events of special interest for atezolizumab in the ABCPem/Pac and BCPem/Pac arms were hepatitis (driven by laboratory abnormalities; mostly low grade), hypothyroidism and rash. Overall,IMpower151 did not meet its primary endpoint (INV-PFS) in metastatic nsqNSCLC. ABCPem/Pac was generally well tolerated, with no new safety signals.
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