在临床试验之外接受一线帕博利珠单抗治疗的PD-L1≥50%的晚期非小细胞肺癌患者5年生存率的决定因素：Pembro-real 5Y全球注册研究结果
Determinants of 5-year survival in patients with advanced NSCLC with PD-L1≥50% treated with first-line pembrolizumab outside of clinical trials: results from the Pembro-real 5Y global registry.
作者信息
Cortellini Alessio, Brunetti Leonardo, Di Fazio Giuseppina Rita, Garbo Edoardo, Pinato David J, Naidoo Jarushka, Katz Artur, Loza Monica, Neal Joel W, Genova Carlo, Gettinger Scott, Kim So Yeon, Jayakrishnan Ritujith, El Zarif Talal, Russano Marco, Pecci Federica, Di Federico Alessandro, Awad Mark, Alessi Joao V, Montrone Michele, Owen Dwight Hall, Signorelli Diego, Fidler Mary Jo, Li Mingjia, Camerini Andrea, De Giglio Andrea, Young Lauren, Vincenzi Bruno, Metro Giulio, Passiglia Francesco, Yendamuri Sai, Guida Annalisa, Ghidini Michele, Awosika Nichola O, Napolitano Andrea, Fulgenzi Claudia A M, Grisanti Salvatore, Grossi Francesco, D'Incecco Armida, Josephides Eleni, Van Hemelrijck Mieke, Russo Alessandro, Gelibter Alain, Spinelli Gianpaolo, Verrico Monica, Tomasik Bartłomiej, Giusti Raffaele, Newsom-Davis Thomas, Bria Emilio, Sebastian Martin, Rost Maximilian, Forster Martin, Mukherjee Uma, Landi Lorenza, Mazzoni Francesca, Aujayeb Avinash, Dupont Manuel, Curioni-Fontecedro Alessandra, Chiari Rita, Pantano Francesco, Morabito Alessandro, Leonetti Alessandro, Friedlaender Alex, Addeo Alfredo, Zoratto Federica, De Tursi Michele, Cantini Luca, Roca Elisa, Mountzios Giannis, Della Gravara Luigi, Kalvapudi Sukumar, Inno Alessandro, Bironzo Paolo, Di Marco Barros Rafael, O'Reilly David, Bell Jack, Karapanagiotou Eleni, Monnet Isabelle, Baena Javier, Macerelli Marianna, Majem Margarita, Agustoni Francesco, Cortinovis Diego Luigi, Tonini Giuseppe, Minuti Gabriele, Bennati Chiara, Mezquita Laura, Gorría Teresa, Servetto Alberto, Beninato Teresa, Lo Russo Giuseppe, Rogado Jacobo, Moliner Laura, Biello Federica, Aboubakar Nana Frank, Dingemans Anne-Marie, Aerts Joachim G J V, Ferrara Roberto, Torri Valter, Hejleh Taher Abu, Takada Kazuki, Naqash Abdul Rafeh, Garassino Marina, Peters Solange, Wakelee Heather, Nassar Amin H, Ricciuti Biagio
机构信息
Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy
Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College London, London, UK.
出版信息
J Immunother Cancer. 2025 Feb 4;13(2):e010674. doi: 10.1136/jitc-2024-010674.
BACKGROUND
Pembrolizumab monotherapy is an established front-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS)≥50%. However, real-world data on its long-term efficacy remains sparse.
METHODS
This study assessed 5-year outcomes of first-line pembrolizumab monotherapy in a large, multicenter, real-world cohort of patients with advanced NSCLC and PD-L1 TPS≥50%, referred to as Pembro-real 5Y. Individual patient-level data (IPD) from the experimental arm of the KEYNOTE-024 trial were extracted (KN024 IPD cohort) to compare the long-term outcomes between the two cohorts. To further assess the reproducibility of clinical trial results, we reconstructed the "KN024 look-alike" cohort by excluding patients with an Eastern Cooperative Oncology Group-performance status (ECOG-PS)≥2, those requiring corticosteroids with doses ≥10 mg of prednisolone/equivalent, patients with positive/unknown epidermal growth factor receptor/anaplastic lymphoma kinase genotype, and those with pre-existing autoimmune disease. We additionally provided a hierarchical organization of determinants of long-term benefit through a conditional inference tree analysis.
RESULTS
The study included 1050 patients from 61 institutions across 14 countries, with a median follow-up of 70.3 months. The 5-year survival rate was 26.9% (95% CI: 23.8% to 30.2%), and median OS was 21.8 months (95% CI: 19.1 to 25.7), while 32 (3.0%) patients who achieved a complete response remained progression-free at the data cut-off. The KN024 look-alike cohort had a 5-year survival rate of 29.3% (95% CI: 25.5% to 33.6%) and a median OS of 27.5 months (95% CI: 22.8 to 31.3). Neither the overall study population nor the KN024 look-alike cohort exhibited significantly different OS compared with the KN024 IPD cohort. By the data cut-off, 1015 patients (96.7%) had permanently discontinued treatment: 659 (64.9%) due to progressive disease, 156 (15.4%) due to toxicity, 77 (7.6%) due to treatment completion, and 106 (10.4%) due to other reasons. Overall, 222 participants (21.1%) were treated for a minimum period of 24 months, among them the 5-year survival rates were: 31.7%, 72.7%, 78.6%, 84.2% for patients who discontinued treatment due to progressive disease, toxicity, treatment completion, and other reasons, respectively.
CONCLUSION
This study provides valuable real-world evidence that confirms the long-term efficacy of pembrolizumab outside of clinical trials. Hierarchical organization indicates ECOG-PS, age and PD-L1-TPS as the most important predictors of 5-year survival, potentially informing clinical practice.
背景
帕博利珠单抗单药疗法是一种已确立的一线治疗方案，用于治疗程序性死亡配体1（PD-L1）肿瘤比例评分（TPS）≥50%的晚期非小细胞肺癌（NSCLC）。然而，关于其长期疗效的真实世界数据仍然稀少。
方法
本研究评估了一线帕博利珠单抗单药疗法在一个大型、多中心、真实世界队列中的5年结局，该队列纳入了晚期NSCLC且PD-L1 TPS≥50%的患者，称为Pembro-real 5Y。提取了KEYNOTE-024试验实验组的个体患者水平数据（IPD）（KN024 IPD队列），以比较两个队列的长期结局。为进一步评估临床试验结果的可重复性，我们通过排除东部肿瘤协作组体能状态（ECOG-PS）≥2的患者、需要剂量≥10 mg泼尼松龙/等效剂量的皮质类固醇的患者、表皮生长因子受体/间变性淋巴瘤激酶基因型为阳性/未知的患者以及患有自身免疫性疾病的患者，重建了“类KN024”队列。我们还通过条件推断树分析提供了长期获益决定因素的分层组织。
结果
该研究纳入了来自14个国家61家机构的1050例患者，中位随访时间为70.3个月。5年生存率为26.9%（95%CI：23.8%至30.2%），中位总生存期（OS）为21.8个月（95%CI：19.1至25.7），而32例（3.0%）达到完全缓解的患者在数据截止时仍无进展。类KN024队列的5年生存率为29.3%（95%CI：25.5%至33.6%），中位OS为27.5个月（95%CI：22.8至31.3）。总体研究人群和类KN024队列与KN024 IPD队列相比，OS均无显著差异。截至数据截止时，1015例患者（96.7%）已永久停药：659例（64.9%）因疾病进展停药，156例（15.4%）因毒性停药，77例（7.6%）因完成治疗停药，106例（10.4%）因其他原因停药。总体而言，222例参与者（21.1%）接受治疗的最短时间为24个月，其中因疾病进展、毒性、完成治疗和其他原因停药的患者5年生存率分别为：31.7%、72.7%、78.6%、84.2%。
结论
本研究提供了有价值的真实世界证据，证实了帕博利珠单抗在临床试验之外的长期疗效。分层组织表明ECOG-PS、年龄和PD-L1-TPS是5年生存的最重要预测因素，可能为临床实践提供参考。
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