在晚期黑色素瘤患者短期增加抗pd1靶向治疗后的持久反应：IMPemBra试验的5年无进展和总生存期更新

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-04-19 DOI:10.1016/j.ejca.2025.115431

L.L. Hoeijmakers , E.A. Rozeman , M. Lopez-Yurda , L.G. Grijpink-Ongering , B.C. Heeres , B.A. van de Wiel , C. Flohil , A. Sari , S.W.T.P.J. Heijmink , D. van den Broek , A. Broeks , J.W.B. de Groot , M.A. Vollebergh , S. Wilgenhof , J.V. van Thienen , J.B.A.G. Haanen , C.U. Blank

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引用次数: 0

摘要

在免疫检查点抑制剂的基础上添加靶向治疗（TT）已被证明可以短暂地增加黑色素瘤的免疫浸润。这形成了IMPemBra试验的基本原理，该试验显示，与单独抗pd1相比，短期/间歇性TT和抗pd1治疗的患者的无进展生存期（PFS）有数值上的增加。在本报告中，将报告最终毒性分析，5年PFS和总生存期（OS）的探索性分析，以及后续治疗的分析。患者和方法32 treatment-naïve BRAFV600E/ k突变的晚期黑色素瘤患者每3周接受2个周期的派姆单抗200 mg治疗，随后随机分组继续派姆单抗单药治疗6周，在队列1中与派姆单抗联合间歇性达非尼150 mg BID + 曲美替尼2 mg QD 2×1-week（队列2）、2×2-weeks（队列3）或1×6-weeks（队列4）中进行比较。在第12周后，所有患者继续派姆单抗单药治疗最多2年。ResultsWith平均73个月的随访中,最终成绩3 - 4的几种不良事件12 %(组1),12 %(组2),38 %(组3)和63年 %(群4)。预计5年PFS和OS利率25 % 50 % pembrolizumab单一疗法(cohort-1)和46 % 71 % pembrolizumab + 间歇TT(军团2 - 4)。估计5年PFS和OS分别为63 %和63 %（队列2），38 %和75 %（队列3），38 %和75 %（队列4）。随后的治疗在队列之间是平衡的。接受短期/间歇性方案治疗的患者在随后的TT治疗中获得了持久的反应。IMPemBra试验的生存更新表明，短期TT和检查点抑制的结合可以诱导持久的反应，值得在更大的队列和随机设计中进一步分析。

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Durable responses upon short-term addition of targeted therapy to anti-PD1 in advanced melanoma patients: 5-year progression-free and overall survival update of the IMPemBra trial

Background

The addition of targeted therapy (TT) to immune checkpoint inhibitors has been shown to transiently increase immune infiltration in melanoma. This formed the rationale for the IMPemBra trial, which showed a numerical increase in progression-free survival (PFS) in patients treated with short-term/intermittent TT and anti-PD1 compared to anti-PD1 alone. In this report, the final toxicity-analysis, 5-year PFS and exploratory analysis of overall survival (OS) will be reported, together with an analysis of subsequent therapies.

Patients and methods

32 treatment-naïve patients with a BRAFV600E/K-mutated advanced melanoma were treated with 2 cycles of pembrolizumab 200 mg every 3 weeks, followed by randomization to continue pembrolizumab monotherapy for six weeks in cohort-1 versus pembrolizumab plus intermittent dabrafenib 150 mg BID + trametinib 2 mg QD 2×1-week (cohort 2), 2×2-weeks (cohort 3), or 1×6-weeks (cohort 4). After week 12, all patients continued pembrolizumab monotherapy for a maximum of 2 years.

Results

With a median follow-up of 73 months, final grade 3–4 immune-related adverse events are 12 % (cohort 1), 12 % (cohort 2), 38 % (cohort 3) and 63 % (cohort 4). Estimated 5-year PFS and OS rates were 25 % and 50 % for pembrolizumab monotherapy (cohort-1) and 46 % and 71 % for pembrolizumab + intermittent TT (cohorts 2–4). Estimated 5-year PFS and OS were 63 % and 63 % (cohort 2), 38 % and 75 % (cohort 3), and 38 % and 75 % (cohort 4), respectively. The subsequent therapies were balanced between cohorts. Patients treated with short-term/intermittent schemes achieved durable responses upon subsequent TT again.

Conclusion

This survival update from the IMPemBra trial demonstrates that combination of short-term TT and checkpoint inhibition can induce long-lasting responses, warranting further analyses in larger cohorts, and in a randomized design.

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

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