Regorafenib Shows High Anti-Tumor Activity as Monotherapy in Advanced, Pre-Treated Thymic Cancer


As part of the larger Resound trial, regorafenib met its primary endpoint in thymic cancer but no patient subset received greater benefits from the drug.

The kinase inhibitor regorafenib (Stivarga) showed high levels of anti-tumor activity in patients with advanced or recurrent thymic cancers, including advanced or recurrent B2-B3 thymoma and thymic carcinoma previously treated with platinum-containing chemotherapy. These results from the phase 2 Resound trial were published recently in Cancer.

Patients in this single-arm trial had an 8-week progression-free survival (PFS) rate of 78.9% (15 of 19 patients). This result rejected the null hypothesis of an 8-week PFS rate ≤ 25% with a type I error of 0.10 and a statistical power of 80% at the alternative hypothesis of an 8-week PFS rate of ≥ 50% (≥ 8 of 19 evaluable patients remaining progression-free at 2 months).

The authors, led by Matteo Perrino, MD, of Humanitas Research Hospital, Milan, Italy, noted that the study met its primary endpoint. “The activity and toxicity profile of regorafenib observed in this small series of thymic epithelial tumors seem to be encouraging and, therefore, should be better evaluated in subsequent larger and specific study phases,” they wrote.

Conducted at two hospitals in Italy, this study enrolled 19 patients, 11 of whom had thymoma and 8 of whom had thymic carcinoma. The patients were divided nearly evenly between those for whom regorafenib was their second-line therapy vs. therapy beyond the second line. All study patients received 160 mg of regorafenib daily in a 4-week cycle (3 weeks on, 1 week off).

According to RECIST criteria, 1 patient achieved a partial response (PR), while 14 patients experienced stable disease (SD). Two patients had progressive disease (PD). Overall, 15 patients (78.9%) experienced disease control (95% Confidence Interval [CI], 54.4%-94.0%).

According to CHOI criteria, 13 patients had a PR, while 2 patients each had SD and PD. Overall, the disease control rate (DCR) was 78.9% (95% CI, 54.4%-94.0%).

In explaining their use of both RECIST and CHOI criteria, the authors wrote,

“The ability to differentiate between response or SD and PD early during therapy is crucial for allowing adjustment of therapy. The CHOI criteria, taking into account the tumor density as well as the diameters, seem to be able to better evaluate those cases in which the cystic change of the lesions is not associated with their significant size reduction.”

The median follow-up was 39.1 months (range, 0.9-43.9 months). The median PFS was 9.6 months (95% CI, 3.6-12.8 months). The 3-month PFS rate was 79%; at 6 months the PFS rate was 57.9%. At 12 months, the PFS rate had dropped to 33.8%.

The median overall survival (OS) was 33.8 months (95% CI, 10.2 months to not evaluable). The 1-and 2-year OS rates were 73.7% and 63.2%, respectively.

About half the patients (52.6%) experienced grade 3-4 treatment-related adverse events (AEs). Hypertension was the most common grade 3-4 AE, affecting 2 patients (10.5%). One patient had a grade 4 increase in lipase values, probably due to concurrent azathioprine use. About two-thirds of patients developed stomatitis (68.4%) and hand-foot skin reaction and asthenia (63.2%). Nearly half the patients (47.3%) required dose reduction; 3 of these patients required the dose reduction to address hand-foot skin reaction. Seven patients stopped treatment temporarily due to side effects.

The authors concluded, “Disappointingly, we are not able to identify a subset of patients potentially benefiting from this drug. In fact, no difference was observed in terms of DCR, PFS, or OS stratifying for age, histology, sex, response to the previous line, and line of therapy.”

Resound (NCT02307500) is a screening trial that investigates the potential role of regorafenib in different cancers after conventional therapies have failed. In addition to thymic malignancies, the trial also examines regorafenib’s effectiveness in pancreatic cancer, ovarian cancer, melanoma, and soft-tissue sarcomas. Thus, the authors characterized this substudy’s primary endpoint as “exploratory only” because it was not specifically targeted toward thymic neoplasms.


Perrino M, De Pas T, Bozzarelli S, et al. Resound Trial: A phase 2 study of regorafenib in patients with thymoma (type B2-B3) and thymic carcinoma previously treated with chemotherapy. Cancer. Published online October 27, 2021.

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