Avelumab/Axitinib Combo May Unlock New Treatment Direction for Rare Thymic Epithelial Tumors


Phase 2 findings indicate that a combination of avelumab and axitinib may draw promising responses in patients with advanced type B3 thymoma and thymic carcinoma.

Avelumab (Bavencio) plus axitinib (Inlyta) displayed encouraging responses among patients with advanced type B3 thymoma and thymic carcinoma who had already received at least 1 cycle of treatment, according to data from an ongoing phase 2 study published in Lancet Oncology.

The results showed that the overall response rate (ORR) was 34% (n = 11/32; 90% CI, 21%-50%). No patients had a complete response, 11 (34%) had a partial response, 18 (56%) had stable disease, and in two patients (6%) progressive disease was the best response.

“Avelumab combined with axitinib has promising anti-tumor activity and acceptable toxicity in patients with advanced type B3 thymoma and thymic carcinoma progressing after chemotherapy and could emerge as a new standard treatment option in this setting,” lead study author Fabio Conforti, MD, medical oncologist at the European Institute of Oncology in Milan, Italy, and coauthors, wrote in the study publication.

Thymic epithelial tumors are rare neoplasms that stem from thymic epithelial cells. Type B thymomas and thymic carcinomas are subtypes of thymic epithelial tumors that are associated with aggressive disease biology, high rates of relapse, and poor overall survival. Notably, patients with advanced type B thymoma and thymic carcinoma with chemotherapy-resistant disease have limited treatment options.

As monotherapy, anti-angiogenesis agents and anti–PD-1/PD-L1 inhibitors have shown encouraging efficacy in patients with type B thymomas and thymic carcinoma, and synergistic activity has been documented in several advanced solid tumors including renal cell carcinoma, hepatocarcinoma, and non–small cell lung cancer.

CAVEATT is a single-arm, multicenter, phase 2 trial conducted at the European Institute of Oncology and the Humanitas Institute in Milan. The study enrolled patients at least 18 years of age with histologically confirmed, advanced type B3 thymoma or thymic carcinoma and disease progression after at least one line of platinum-based chemotherapy. Patients also had to have an ECOG performance status from 0 to 2 and measurable disease according to RECIST v1.1 criteria.

Prior treatment with an antiangiogenesis drug was allowed as long as it was not administered in combination with an immune checkpoint inhibitor. Patients with asymptomatic, treated, non-progressive brain metastases not requiring steroid treatment were also eligible.

Eligible patients received 10 mg/kg of intravenous avelumab every 2 weeks and 5 mg of oral axitinib twice daily until disease progression or unacceptable toxicity. Notably, avelumab was administered following oral premedication with 50 mg of diphenhydramine and 500 mg of paracetamol.

The primary end point was centrally assessed ORR according to RECIST v1.1 criteria. Patients who received at least 1 cycle of treatment and had at least 1 CT scan after starting treatment were evaluable for response and were included in the efficacy and safety analyses. Key secondary end points included PFS, 6-month PFS, and safety.

Thirty-two patients enrolled from April 22, 2019, to June 30, 2021. The median age of patients was 62 years (interquartile range [IQR], 49-71) and most were men (59%). Twenty-seven (84%) patients had thymic carcinoma, 3 (9%) had type B3 thymoma, and 2 (6%) had mixed type B3 thymoma and thymic carcinoma tumor.

Fourteen (43%) patients underwent surgery prior to enrollment and most patients had extensive metastatic disease. The median number of prior lines of therapy was 2 (IQR, 1-2) and 13 (41%) patients had received prior treatment with an anti-angiogenesis drug.

Twenty-five (78%) patients died by the February 1, 2022, data cutoff. Four (13%) patients remained on treatment. At a median follow-up of 22.4 months (IQR, 12.3-24.3), the median PFS was 7.5 months (90% CI, 3.7-10.0). The 6-month PFS rate was 61.3% (90% CI, 45.3%-73.9%).

In terms of safety, most adverse effects (AEs) were grade 1 or 2. Grade 1 or 2 infusion-related reactions associated with avelumab occurred in 3 (9%) patients.

“The toxicity profile of the avelumab and axitinib combination was acceptable and consistent with that already reported in several other trials,” the authors wrote.

The most frequent grade 3/4 AE was hypertension (19%). Eight (25%) patients required axitinib dose reductions because of AEs. Four (12%) patients developed serious AEs that were classified as new-onset immune-related AEs, including 1 case of grade 3 interstitial pneumonitis, 1 case of grade 4 polymyositis, and 2 cases of grade 3 polymyositis—all required treatment discontinuation. No treatment-related deaths occurred.

“The ongoing multicentre PECATI trial [NCT04710628], testing the combination of pembrolizumab [Keytruda] and lenvatinib [Lenvima] in a similar patient population, will provide further evidence on the activity of the combination of anti-angiogenic agents plus immune checkpoint inhibitors,” the authors concluded.


Conforti F, Zucali PA, Pala L, et al. Avelumab plus axitinib in unresectable or metastatic type B3 thymomas and thymic carcinomas (CAVEATT): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(10):1287-1296. doi:10.1016/S1470-2045(22)00542-3

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