Luke Jason J, Ascierto Paolo A, Khattak Muhammad A, Rutkowski Piotr, Del Vecchio Michele, Spagnolo Francesco, Mackiewicz Jacek, Merino Luis de la Cruz, Chiarion-Sileni Vanna, Kirkwood John M, Robert Caroline, Schadendorf Dirk, de Galitiis Federica, Carlino Matteo S, Dummer Reinhard, Mohr Peter, Odeleye-Ajakaye Amos, Fukunaga-Kalabis Mizuho, Krepler Clemens, Eggermont Alexander M M, Long Georgina V
UPMC Hillman Cancer Center and University of Pittsburgh, Pittsburgh, PA, USA.
Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy.
Eur J Cancer. 2025 May 2;220:115381. doi: 10.1016/j.ejca.2025.115381. Epub 2025 Mar 23.
Adjuvant pembrolizumab prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB/IIC melanoma in KEYNOTE-716. Results of a post hoc 4-year analysis are reported, including progression/recurrence-free survival 2 (PRFS2).
Patients were randomly assigned 1:1 to pembrolizumab 200 mg or placebo intravenously every 3 weeks (part 1). RFS was the primary end point; DMFS was secondary. Patients with recurrence following placebo or 17 cycles of pembrolizumab could cross over to or be rechallenged with pembrolizumab (part 2).
Median follow-up (n = 976) was 52.8 months (range, 39.4-64.8). RFS (HR, 0.62 [95 % CI, 0.50-0.78]) and DMFS (HR, 0.59 [0.45-0.77]) favored pembrolizumab. At 48 months, RFS rates were 71.3 % for pembrolizumab and 58.3 % for placebo, and DMFS rates were 81.0 % and 70.1 %, respectively. The HR for PRFS2 was 0.75 (95 % CI, 0.56-1.01); 48-month PRFS2 rates were 82.5 % for pembrolizumab and 76.7 % for placebo. In the crossover population, median follow-up was 36.9 months; median RFS was not reached (NR; 95 % CI, 16.8-NR; 48-month RFS, 50.6 %) in patients with resectable disease (n = 41) and median progression-free survival was 22.0 months (4.5-NR) in patients with unresectable disease (n = 30). Among patients rechallenged, median follow-up was 21.9 months; none with resectable disease had recurrence (n = 6) and 1 with unresectable disease had best response of stable disease (n = 3). No new safety signals were observed.
With > 4 years follow-up, pembrolizumab continued to prolong RFS and DMFS and had antitumor activity in patients who crossed over to pembrolizumab.
NCT03553836.
在KEYNOTE-716研究中，辅助性帕博利珠单抗可延长IIB/IIC期黑色素瘤切除术后患者的无复发生存期（RFS）和无远处转移生存期（DMFS）。本文报告了一项事后4年分析的结果，包括无进展/无复发生存期2（PRFS2）。
患者按1:1随机分配，每3周静脉注射200mg帕博利珠单抗或安慰剂（第1部分）。RFS是主要终点；DMFS是次要终点。接受安慰剂或17个周期帕博利珠单抗治疗后复发的患者可以交叉接受或再次接受帕博利珠单抗治疗（第2部分）。
中位随访时间（n = 976）为52.8个月（范围39.4 - 64.8个月）。RFS（风险比[HR]，0.62[95%置信区间（CI），0.50 - 0.78]）和DMFS（HR，0.59[0.45 - 0.77]）倾向于帕博利珠单抗。在48个月时，帕博利珠单抗组的RFS率为71.3%，安慰剂组为58.3%，DMFS率分别为81.0%和70.1%。PRFS2的HR为0.75（95%CI，0.56 - 1.01）；48个月时，帕博利珠单抗组的PRFS2率为82.5%，安慰剂组为76.7%。在交叉治疗人群中，中位随访时间为36.9个月；可切除疾病患者（n = 41）的中位RFS未达到（NR；95%CI，16.8 - NR；48个月RFS，50.6%），不可切除疾病患者（n = 30）的中位无进展生存期为22.0个月（4.5 - NR）。在再次接受治疗的患者中，中位随访时间为21.9个月；可切除疾病患者中无一例复发（n = 6），不可切除疾病患者中有1例最佳反应为病情稳定（n = 3）。未观察到新的安全信号。
经过超过4年的随访，帕博利珠单抗持续延长RFS和DMFS，并对交叉接受帕博利珠单抗治疗的患者具有抗肿瘤活性。
NCT03553836
