RT Journal Article
SR Electronic
T1 A Pilot Study of Galunisertib plus Stereotactic Body Radiotherapy in Patients with Advanced Hepatocellular Carcinoma
JF Molecular Cancer Therapeutics
JO Mol Cancer Ther
FD American Association for Cancer Research
SP 389
OP 397
DO 10.1158/1535-7163.MCT-20-0632
VO 20
IS 2
A1 Reiss, Kim A.
A1 Wattenberg, Max M.
A1 Damjanov, Nevena
A1 Prechtel Dunphy, Elizabeth
A1 Jacobs-Small, Mona
A1 Lubas, M. Judy
A1 Robinson, James
A1 Dicicco, Lisa
A1 Garcia-Marcano, Luis
A1 Giannone, Michael A.
A1 Karasic, Thomas B.
A1 Furth, Emma E.
A1 Carpenter, Erica L.
A1 Wojcieszynski, Andrzej P.
A1 Vonderheide, Robert H.
A1 Beatty, Gregory L.
A1 Ben-Josef, Edgar
YR 2021
UL http://mct.aacrjournals.org/content/20/2/389.abstract
AB TGFβ is a pleiotropic cytokine with immunosuppressive activity. In preclinical models, blockade of TGFβ enhances the activity of radiation and invokes T-cell antitumor immunity. Here, we combined galunisertib, an oral TGFβ inhibitor, with stereotactic body radiotherapy (SBRT) in patients with advanced hepatocellular carcinoma (HCC) and assessed safety, efficacy, and immunologic correlatives. Patients (n = 15) with advanced HCC who progressed on, were intolerant of, or refused sorafenib were treated with galunisertib (150 mg orally twice a day) on days 1 to 14 of each 28-day cycle. A single dose of SBRT (18-Gy) was delivered between days 15 to 28 of cycle 1. Site of index lesions treated with SBRT included liver (9 patients), lymph node (4 patients), and lung (2 patients). Blood for high-dimensional single cell profiling was collected. The most common treatment-related adverse events were fatigue (53%), abdominal pain (46.6%), nausea (40%), and increased alkaline phosphatase (40%). There were two instances of grade 2 alkaline phosphatase increase and two instances of grade 2 bilirubin increase. One patient developed grade 3 achalasia, possibly related to treatment. Two patients achieved a partial response. Treatment with galunisertib was associated with a decrease in the frequency of activated T regulatory cells in the blood. Distinct peripheral blood leukocyte populations detected at baseline distinguished progressors from nonprogressors. Nonprogressors also had increased CD8+PD-1+TIGIT+ T cells in the blood after treatment. We found galunisertib combined with SBRT to be well tolerated and associated with antitumor activity in patients with HCC. Pre- and posttreatment immune profiling of the blood was able to distinguish patients with progression versus nonprogression.This article is featured in Highlights of This Issue, p. 217