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Clinical Trial
. 2023 Oct 1;153(7):1413-1422.
doi: 10.1002/ijc.34649. Epub 2023 Jul 10.

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

Laurien J Zeverijn  1   2 , Eleonora J Looze  3 , Subotheni Thavaneswaran  4   5   6 , J Maxime van Berge Henegouwen  2   7 , Robert J Simes  6 , Louisa R Hoes  1   2 , Katrin M Sjoquist  6 , Hanneke van der Wijngaart  2   8 , Lucille Sebastian  6 , Birgit S Geurts  1   2 , Chee K Lee  6 , Gijsbrecht F de Wit  1   2 , David Espinoza  6 , Paul Roepman  9 , Frank P Lin  4   5   6 , Anne M L Jansen  10 , Wendy W J de Leng  10 , Vincent van der Noort  11 , Lindsay V M Leek  1   2   12 , Filip Y F L de Vos  13 , Carla M L van Herpen  14 , Hans Gelderblom  7 , Henk M W Verheul  15 , David M Thomas  4   5 , Emile E Voest  1   2   16
Affiliations
Clinical Trial

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

Laurien J Zeverijn et al. Int J Cancer. .

Abstract

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.

Trial registration: ClinicalTrials.gov NCT02925234.

Keywords: CDK4/6 inhibitors; drug rediscovery; monotherapy; precision oncology; targeted therapy.

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References

REFERENCES

    1. van der Velden DL, Hoes LR, van der Wijngaart H, et al. The drug rediscovery protocol facilitates the expanded use of existing anticancer drugs. Nature. 2019;574:127-131.
    1. Thavaneswaran S, Sebastian L, Ballinger M, et al. Cancer molecular screening and therapeutics (MoST): a framework for multiple, parallel signal-seeking studies of targeted therapies for rare and neglected cancers. Med J Aust. 2018;209:354-355.
    1. Turner NC, Ro J, André F, et al. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015;373:209-219.
    1. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375:1738-1748.
    1. Goetz MP, Toi M, Campone M, et al. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35:3638-3646.

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