Murianni Veronica, Signori Alessio, Buti Sebastiano, Rebuzzi Sara Elena, Bimbatti Davide, De Giorgi Ugo, Chiellino Silvia, Galli Luca, Zucali Paolo Andrea, Masini Cristina, Naglieri Emanuele, Procopio Giuseppe, Milella Michele, Fratino Lucia, Baldessari Cinzia, Ricotta Riccardo, Mollica Veronica, Sorarù Mariella, Tudini Marianna, Prati Veronica, Malgeri Andrea, Atzori Francesco, Di Napoli Marilena, Caffo Orazio, Spada Massimiliano, Morelli Franco, Prati Giuseppe, Nolè Franco, Vignani Francesca, Cavo Alessia, Lipari Helga, Roviello Giandomenico, Catalano Fabio, Damassi Alessandra, Cremante Malvina, Rescigno Pasquale, Fornarini Giuseppe, Banna Giuseppe Luigi
Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genoa, Genoa, Italy.
Front Oncol. 2024 Feb 12;14:1307635. doi: 10.3389/fonc.2024.1307635. eCollection 2024.
BACKGROUND: Immunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy. METHODS: The Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS. RESULTS: Overall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 - 10.1), while mPFS was 7.0 months (95% CI: 5.7 - 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p < 0.001) and overall survival (OS) (34.8 vs 17.9 months; < 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; = 0.075) and disease control rate (61.3% vs 55.5%; = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59). CONCLUSION: We found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS.
背景：与化疗和靶向治疗相比，免疫疗法呈现出独特的癌症反应模式。一些患者在初始病情进展后出现疾病反应，或在治疗中断后出现持久反应。在临床实践中，如果观察到临床获益，免疫检查点抑制剂在影像学进展后可能会继续使用。因此，基于首次疾病进展来估计无进展生存期（PFS）可能无法准确反映免疫疗法的实际获益。 方法：Meet-URO 15研究是一项对571例接受纳武单抗治疗的预处理转移性肾细胞癌（mRCC）患者进行的多中心回顾性分析。策略失败时间（TSF）定义为从免疫治疗开始到明确的疾病进展或死亡的时间间隔。该分析将TSF与PFS进行比较，并评估进展后治疗（TBP）和非TBP患者之间的反应和生存结果。此外，我们基于TSF和PFS评估了Meet-URO评分与国际转移性肾细胞癌数据库联盟（IMDC）评分的预后准确性。 结果：总体而言，571例mRCC患者纳入分析。中位TSF为8.6个月（95%CI：7.0 - 10.1），而中位PFS为7.0个月（95%CI：5.7 - 8.5）。TBP患者（N = 93）的TSF（16.3对5.5个月；p < 0.001）和总生存期（OS）（34.8对17.9个月；< 0.001）显著更长，但与非TBP患者的PFS相似。在TBP患者中，观察到从首次到明确疾病进展的中位延迟为9.6个月（范围：6.7 - 16.3），而非TBP患者的中位TSF和PFS重叠（5.5个月）。此外，TBP患者的总体缓解率（33.3%对24.3%； = 0.075）和疾病控制率（61.3%对55.5%； = 0.31）有更高的趋势。最后，在整个人群中，Meet-URO评分在预测TSF（c指数：0.63对0.59）和PFS（0.62对0.59）方面优于IMDC评分。 结论：我们发现接受纳武单抗治疗的mRCC患者的中位TSF和中位PFS之间存在2个月的差异。然而，TBP患者有更好的结果，包括TSF和OS明显长于非TBP患者。Meet-URO评分是TSF和PFS的可靠预测指标。
JAMA Netw Open. 2023-11-1
Cancer Immunol Immunother. 2022-8
Ther Adv Med Oncol. 2021-9-11
N Engl J Med. 2021-3-4
Zotero 插件