Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8

Hecht M, Gostian AO, Eckstein M, Rutzner S, Von Der Grün J, Illmer T, Hautmann MG, Klautke G, Laban S, Brunner T, Hinke A, Becker I, Frey B, Semrau S, Geppert CI, Hartmann A, Balermpas P, Budach W, Gaipl U, Iro H, Fietkau R (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Book Volume: 8

Journal Issue: 2

DOI: 10.1136/jitc-2020-001378

Abstract

BACKGROUND: To determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer. METHODS: Patients received a single cycle of cisplatin 30 mg/m² on days 1-3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab. The objective of this interim analysis was to analyze safety and efficacy of the chemoimmunotherapy-induction treatment before radioimmunotherapy. RESULTS: A total of 57 patients were enrolled, 56 were treated. Median pretreatment intratumoral CD8+ cell density was 342 cells/mm². After induction treatment, 27 patients (48%) had a pCR in the rebiopsy and further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3-4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3-4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm², 95% CI 1.0001 to 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR. CONCLUSIONS: Single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.

Authors with CRIS profile

Involved external institutions

Universität Ulm Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE) Universität Regensburg Germany (DE) Onkozentrum Dresden/Freiberg Germany (DE) Klinikum Chemnitz Germany (DE) Otto-von-Guericke-Universität Magdeburg Germany (DE)

How to cite

APA:

Hecht, M., Gostian, A.O., Eckstein, M., Rutzner, S., Von Der Grün, J., Illmer, T.,... Fietkau, R. (2020). Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8. Journal for ImmunoTherapy of Cancer, 8(2). https://dx.doi.org/10.1136/jitc-2020-001378

MLA:

Hecht, Markus, et al. "Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8." Journal for ImmunoTherapy of Cancer 8.2 (2020).

BibTeX: Download