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000302818 1001_ $$0P:(DE-He78)4e4e534b615747750de8b9a7afdd8f56$$aTeleanu, Maria-Veronica$$b0$$eFirst author$$udkfz
000302818 245__ $$aCDK4/6 inhibition in advanced chordoma: final results of the NCT PMO-1601 trial.
000302818 260__ $$a[London]$$bElsevier$$c2025
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000302818 520__ $$aThis study aims to evaluate antitumor response of palbociclib in patients with advanced chordoma, an ultra-rare cancer without approved systemic therapy. Previous data showed that palbociclib reduced cell viability and proliferation in CDKN2A-deficient chordoma cell lines.We conducted a phase II single-arm, open-labeled trial on palbociclib in adult patients with advanced chordomas with p16 (by immunohistochemistry) or CDKN2A (by genomic analysis) loss along with retained CDK4/6 and RB1 expression (by immunohistochemistry or RNA sequencing). Based on CDK4/6/pRB (S780) immunohistochemical expression patterns, a responder versus non-responder signature was assigned. The study used a Simon optimal two-stage design with the primary endpoint of disease control rate (DCR) by RECISTv1.1 after six cycles. Secondary endpoints included progression-free survival, overall survival, and biomarker analysis. The study was considered positive if 25% of patients reached the primary endpoint.Twenty-eight patients with a median age of 59 years were assessed for the primary endpoint. After a median follow-up of 28 months, the DCR was 39%, with 11 patients achieving stable diseases. No objective responses were obtained. The median progression-free survival was 5.6 months, and the median overall survival was 24.6 months. Treatment was well tolerated without new safety signals. There was no correlation between immunohistochemical responder phenotypes and outcome. Biomarker analysis identified additional clinically actionable alterations affecting PIK3CA, PTEN, MTAP, or MET genes, and druggable pathways by transcriptomic analysis.Although antitumor activity was modest, the trial met its primary endpoint. Molecularly tailored combination therapies should be considered in the future to improve efficacy.
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000302818 650_7 $$2Other$$aCDK4/6 inhibition
000302818 650_7 $$2Other$$aCDKN2A/p16 inactivation
000302818 650_7 $$2Other$$aadvanced chordoma
000302818 650_7 $$2Other$$amulticenter phase II trial
000302818 650_7 $$2Other$$apalbociclib
000302818 7001_ $$0P:(DE-He78)42b6114cd48e033299b2b6ef4bf56cc6$$aHeilig, Christoph$$b1$$udkfz
000302818 7001_ $$aPirmann, S.$$b2
000302818 7001_ $$0P:(DE-HGF)0$$aHamacher, R.$$b3
000302818 7001_ $$0P:(DE-HGF)0$$aBauer, S.$$b4
000302818 7001_ $$aGaidzik, V. I.$$b5
000302818 7001_ $$aMayer-Steinacker, R.$$b6
000302818 7001_ $$aAl-Sabah, J.$$b7
000302818 7001_ $$aRoldan Pinzon, S. S. L.$$b8
000302818 7001_ $$aSüße, H.$$b9
000302818 7001_ $$aFreitag, A.$$b10
000302818 7001_ $$0P:(DE-He78)5ea1944c122bc098a81df27a05572719$$aHorak, Peter$$b11$$udkfz
000302818 7001_ $$0P:(DE-He78)e5972dddc3c8d1412db29ba54fed83ba$$aKreutzfeldt, Simon$$b12
000302818 7001_ $$aHutter, B.$$b13
000302818 7001_ $$aHüllein, J.$$b14
000302818 7001_ $$0P:(DE-He78)82090937e7b88ac8ec70bbc40ad6b512$$aSedlaczek, Oliver$$b15$$udkfz
000302818 7001_ $$aLehner, B.$$b16
000302818 7001_ $$aEgerer, G.$$b17
000302818 7001_ $$aJäger, D.$$b18
000302818 7001_ $$aMüller-Tidow, C.$$b19
000302818 7001_ $$0P:(DE-He78)a5218e4871866cd5ab2312e594ca403d$$aHübschmann, Daniel$$b20$$udkfz
000302818 7001_ $$avon Kalle, C.$$b21
000302818 7001_ $$aBarth, T. F. E.$$b22
000302818 7001_ $$0P:(DE-He78)f0144d171d26dbedb67c9db1df35629d$$aFröhling, Stefan$$b23$$eLast author
000302818 7001_ $$aSchlenk, R. F.$$b24
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