Saal Jonas, Eckstein Markus, Ritter Manuel, Brossart Peter, Hölzel Michael, Grünwald Viktor, Klümper Niklas
Medical Clinic III for Oncology, Hematology, Immune-Oncology and Rheumatology, University Hospital Bonn (UKB), Germany; Institute of Experimental Oncology, University Hospital Bonn (UKB), Bonn, Germany; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Germany.
Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany; Comprehensive Cancer Center EMN, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Bavarian Center for Cancer Research (Bayerisches Zentrum für Krebsforschung, BZKF), Germany.
Eur J Cancer. 2025 Jan 17;215:115163. doi: 10.1016/j.ejca.2024.115163. Epub 2024 Dec 6.
Treatment beyond progression (TBP) is common in patients treated with immune-checkpoint inhibitors (ICI), however, there is no biomarker to select patients that are more likely to derive benefit from TBP. Here, we investigated the potential of the modified Glasgow Prognostic Score (mGPS) as a predictive biomarker to select patients for TBP.
We performed a post-hoc analysis of the immunotherapy arms in the randomized phase 3 trials IMmotion151 (renal cell carcinoma), OAK (non-small cell lung cancer) and IMvigor211 (urothelial cancer). The main outcome was post-progression overall survival (PPOS) after the first investigator-assessed disease progression (PD), in mGPS risk groups. The mGPS classifies patients into three risk groups based on C-reactive protein (CRP) and albumin.
We found a strong prognostic value for the mGPS when assessed at the time of PD (PD-mGPS) in all three trials. High-risk PD-mGPS was associated with significantly shorter PPOS compared to low-risk PD-mGPS (HR for death 18.3 (95 % CI 6.71-50.0, p < 0.001)) for RCC, UC: HR 4.16 (95 % CI 2.58-6.69, p < 0.001) and NSCLC HR 2.53 (95 % CI 1.70-3.77, p < 0.001). Importantly, patients within all three trials only derived benefit from ICI-TBP compared to switch to further-line treatment in the PD-mGPS low-risk group (RCC: HR 0.18 (95 % CI 0.06-0.55, p = 0.002); UC: HR 0.59 (95 % CI 0.34-1.00, p = 0.052); NSCLC: 0.62 (0.41-0.92, p = 0.018) compared to PD-mGPS intermediate/ high risk).
These findings suggest that the mGPS measured at the time of radiologic PD can identify patients with a better prognosis who may benefit from continued atezolizumab therapy, aiding in the selection for TBP in clinical practice.
在接受免疫检查点抑制剂（ICI）治疗的患者中，疾病进展后治疗（TBP）很常见，然而，目前尚无生物标志物可用于选择更可能从TBP中获益的患者。在此，我们研究了改良格拉斯哥预后评分（mGPS）作为预测生物标志物以选择TBP患者的潜力。
我们对随机3期试验IMmotion151（肾细胞癌）、OAK（非小细胞肺癌）和IMvigor211（尿路上皮癌）的免疫治疗组进行了事后分析。主要结局是在首次研究者评估的疾病进展（PD）后，mGPS风险组中的进展后总生存期（PPOS）。mGPS根据C反应蛋白（CRP）和白蛋白将患者分为三个风险组。
在所有三项试验中，我们发现在PD时评估的mGPS（PD-mGPS）具有很强的预后价值。与低风险PD-mGPS相比（肾细胞癌死亡风险比为18.3（95%CI 6.71-50.0，p<0.001）），高风险PD-mGPS与显著更短的PPOS相关；尿路上皮癌：风险比为4.16（95%CI 2.58-6.69，p<0.001），非小细胞肺癌风险比为2.53（95%CI 1.70-3.77，p<0.001）。重要的是，与在PD-mGPS中/高风险组中转为接受后续治疗相比，所有三项试验中的患者仅在PD-mGPS低风险组中从ICI-TBP中获益（肾细胞癌：风险比为0.18（95%CI 0.06-0.55，p=0.002）；尿路上皮癌：风险比为0.59（95%CI 0.34-1.00，p=0.052）；非小细胞肺癌：0.62（0.41-0.92，p=0.018））。
这些发现表明，在影像学PD时测量的mGPS可以识别出预后较好、可能从持续阿特珠单抗治疗中获益的患者，有助于在临床实践中选择TBP患者。
