Pembrolizumab与ipilimumab治疗晚期黑色素瘤：KEYNOTE-006研究III期10年随访。

IF 56.7 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2024-12-01 Epub Date: 2024-09-15 DOI:10.1016/j.annonc.2024.08.2330

G V Long, M S Carlino, C McNeil, A Ribas, C Gaudy-Marqueste, J Schachter, M Nyakas, D Kee, T M Petrella, A Blaustein, M Lotem, A M Arance, A I Daud, O Hamid, J Larkin, L Yao, R Singh, R Lal, C Robert

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The primary endpoint was OS; modified progression-free survival (PFS; censored at date last known alive), modified PFS on second-course pembrolizumab, and melanoma-specific survival were exploratory.Results: Of 834 patients randomly assigned in KEYNOTE-006 (pembrolizumab, n = 556; ipilimumab, n = 278), 333 (39.9%) were eligible for KEYNOTE-587; 211/333 patients (25.3%) transitioned to KEYNOTE-587 (pembrolizumab, n = 159; ipilimumab, n = 52) and 122 (14.6%) did not. For patients who transitioned to KEYNOTE-587 (n = 211), median time from randomization in KEYNOTE-006 to data cut-off for KEYNOTE-587 (1 May 2024) was 123.7 months (range, 122.0-127.3 months). Median OS was 32.7 months [95% confidence interval (CI) 24.5-41.6 months] for pembrolizumab and 15.9 months (95% CI 13.3-22.0 months) for ipilimumab [hazard ratio (HR), 0.71 (95% CI 0.60-0.85)]; 10-year OS was 34.0% and 23.6%, respectively. Among patients who completed ≥94 weeks of pembrolizumab, median OS from week 94 was not reached (NR; 95% CI NR-NR); 8-year OS rate was 80.8%. Median modified PFS was 9.4 months (95% CI 6.7-11.6 months) for pembrolizumab and 3.8 months (2.9-4.3 months) for ipilimumab [HR, 0.64 (95% CI 0.54-0.75)]. Among patients who received second-course pembrolizumab, median modified PFS from start of second course was 51.8 months (95% CI 11.0 months-NR); 6-year modified PFS was 49.2%. 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引用次数: 0

摘要

研究背景在KEYNOTE-006（NCT01866319）研究中，Pembrolizumab与伊匹单抗相比可明显改善不可切除的晚期黑色素瘤患者的总生存期（OS）；现提供10年随访数据：不可切除的III期或IV期黑色素瘤患者被随机分配（1:1:1）至pembrolizumab 10 mg/kg i.v. 每2周或每3周一次，持续≤2年（汇总），或ipilimumab 3 mg/kg i.v. 每3周一次，持续4个周期。在KEYNOTE-006之后，患者可转入KEYNOTE-587（NCT03486873）进行长期随访。符合条件的患者可以接受第二疗程的pembrolizumab治疗。主要终点为OS；改良无进展生存期（PFS；以最后已知存活日期为截止日期）、接受第二疗程pembrolizumab的改良PFS以及黑色素瘤特异性生存期为探索性终点：在KEYNOTE-006随机分配的834名患者（pembrolizumab，556人；ipilimumab，278人）中，有333人（39.9%）符合KEYNOTE-587的条件；211/333名患者（25.3%）转入KEYNOTE-587（pembrolizumab，159人；ipilimumab，52人），122人（14.6%）未转入KEYNOTE-587。对于转入KEYNOTE-587的患者（n = 211），从KEYNOTE-006随机化到KEYNOTE-587数据截止（2024年5月1日）的中位时间为123.7个月（范围为122.0-127.3个月）。pembrolizumab的中位OS为32.7个月[95%置信区间（CI）为24.5-41.6个月]，ipilimumab为15.9个月（95% CI为13.3-22.0个月）[危险比（HR）为0.71（95% CI为0.60-0.85）]；10年OS分别为34.0%和23.6%。在完成彭博利珠单抗治疗≥94周的患者中，第94周起的中位OS未达到（NR；95% CI NR-NR）；8年OS率为80.8%。pembrolizumab的中位改良PFS为9.4个月（95% CI 6.7-11.6个月），ipilimumab为3.8个月（2.9-4.3个月）[HR，0.64（95% CI 0.54-0.75）]。在接受第二疗程pembrolizumab治疗的患者中，自第二疗程开始的中位改良PFS为51.8个月（95% CI 11.0个月-NR）；6年改良PFS为49.2%。pembrolizumab的中位黑色素瘤特异性生存期为51.9个月（95% CI 30.0-114.7个月），ipilimumab为17.2个月（13.9-25.9个月）[HR，0.66（95% CI 0.55-0.81）]：这些结果证实，pembrolizumab可为晚期黑色素瘤患者带来长期生存益处，支持将其作为该领域的标准治疗方法。

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Pembrolizumab versus ipilimumab for advanced melanoma: 10-year follow-up of the phase III KEYNOTE-006 study.

Background: Pembrolizumab significantly improved overall survival (OS) versus ipilimumab for unresectable advanced melanoma in KEYNOTE-006 (NCT01866319); 10-year follow-up data are presented.

Patients and methods: Patients with unresectable stage III or IV melanoma were randomly assigned (1:1:1) to pembrolizumab 10 mg/kg i.v. every 2 weeks or every 3 weeks for ≤2 years (pooled), or ipilimumab 3 mg/kg i.v. every 3 weeks for four cycles. After KEYNOTE-006, patients could transition to KEYNOTE-587 (NCT03486873) for long-term follow-up. Eligible patients could receive second-course pembrolizumab. The primary endpoint was OS; modified progression-free survival (PFS; censored at date last known alive), modified PFS on second-course pembrolizumab, and melanoma-specific survival were exploratory.

Results: Of 834 patients randomly assigned in KEYNOTE-006 (pembrolizumab, n = 556; ipilimumab, n = 278), 333 (39.9%) were eligible for KEYNOTE-587; 211/333 patients (25.3%) transitioned to KEYNOTE-587 (pembrolizumab, n = 159; ipilimumab, n = 52) and 122 (14.6%) did not. For patients who transitioned to KEYNOTE-587 (n = 211), median time from randomization in KEYNOTE-006 to data cut-off for KEYNOTE-587 (1 May 2024) was 123.7 months (range, 122.0-127.3 months). Median OS was 32.7 months [95% confidence interval (CI) 24.5-41.6 months] for pembrolizumab and 15.9 months (95% CI 13.3-22.0 months) for ipilimumab [hazard ratio (HR), 0.71 (95% CI 0.60-0.85)]; 10-year OS was 34.0% and 23.6%, respectively. Among patients who completed ≥94 weeks of pembrolizumab, median OS from week 94 was not reached (NR; 95% CI NR-NR); 8-year OS rate was 80.8%. Median modified PFS was 9.4 months (95% CI 6.7-11.6 months) for pembrolizumab and 3.8 months (2.9-4.3 months) for ipilimumab [HR, 0.64 (95% CI 0.54-0.75)]. Among patients who received second-course pembrolizumab, median modified PFS from start of second course was 51.8 months (95% CI 11.0 months-NR); 6-year modified PFS was 49.2%. Median melanoma-specific survival was 51.9 months (95% CI 30.0-114.7 months) for pembrolizumab and 17.2 months (13.9-25.9 months) for ipilimumab [HR, 0.66 (95% CI 0.55-0.81)].

Conclusions: These results confirm that pembrolizumab provides long-term survival benefits in advanced melanoma, supporting it as a standard of care in this setting.

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.