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Treatment with avelumab (Bavencio) plus axitinib (Inlyta) showed promising efficacy and safety in patients with unresectable or metastatic type B3 thymoma and thymic carcinoma, according to a single-arm phase II study.

Among 32 patients across two Italian centers, the overall response rate was 34% (90% CI 21-50), reported Fabio Conforti, MD, of the European Institute of Oncology in Milan, and colleagues.

While no patients achieved complete response, 11 had a partial response and 18 had stable disease, they noted in .

"This is the first prospective trial showing promising antitumor activity for the combination of an anti-PD-L1 or anti-PD-1 drug with an anti-angiogenesis agent in patients with pathologically confirmed, advanced type B3 thymoma or thymic carcinoma," Conforti and team wrote. "Therefore, this combination has the potential to emerge as a standard treatment option in this setting."

In post-hoc analyses, the median time to response was 3.6 months, the median duration of response was 5.5 months, and the disease control rate was 91%.

At a median follow-up of 22.4 months, median progression-free survival (PFS) was 7.5 months, the 6-month PFS rate was 61.3%, and the 12-month PFS rate was 29.0%. Median overall survival (OS) was 26.6 months, and the 12-month and 24-month OS rates were 82.7% and 52.2%, respectively.

Conforti and colleagues called these outcomes "clinically remarkable ... considering the dismal prognosis of the patients' population enrolled, due to the high baseline disease burden and the considerable number of previous lines of therapy received."

Of note, antitumor activity was higher in patients naive to anti-angiogenesis agents compared with those previously treated with the drugs, the authors said. In the 19 patients naive to these agents, the overall response rate was 47% and the disease control rate was 100%, while in the 13 patients previously treated with the drugs, these rates were 15% and 77%, respectively.

Regarding safety, the most common grade 3 or 4 adverse event was hypertension (grade 3 in 19% of patients). Eight patients required axitinib dose reductions due to adverse events. Four patients developed serious new-onset immune-related adverse events, including one with grade 3 interstitial pneumonitis, one with grade 4 polymyositis, and two with grade 3 polymyositis. There were no treatment-related deaths.

"These initial safety results must be cautiously interpreted, because the cohort was comprised of selected patients treated for a relatively short period of time in a phase II study," noted Yasushi Shintani, MD, PhD, and Soichiro Funaki, MD, both of the Osaka University Graduate School of Medicine in Japan, in a . "An investigation with a larger number of patients comprised of a more diverse population with longer durations of treatment will be necessary."

"In addition, a key aspect when choosing treatment for malignant disease is cost. There is no reliable molecular biomarker, such as PD-L1 expression or tumor mutation burden, available at this time, thus predictive markers of the efficacy of combination therapy must be determined to define subsets of patients that are most likely to benefit and for a full assessment of cost effectiveness in the future," they wrote.

To be eligible for this trial, patients had to have a confirmed pathological diagnosis of type B3 thymoma or thymic carcinoma, an advanced stage of disease, and to have progressed after at least one line of platinum-based chemotherapy.

Patients received avelumab at 10 mg/kg intravenously every 2 weeks after premedication with diphenhydramine 50 mg and paracetamol 500 mg orally. Axitinib 5 mg was administered orally twice per day continuously.

Nearly 60% of patients were men, and median age was 62 years. Of the 32 patients in the study, 27 had a thymic carcinoma, three had a type B3 thymoma, and two had a mixed type B3 thymoma and thymic carcinoma tumor.

Fourteen patients underwent surgery before study enrollment, and most had extensive metastatic disease. The median number of previous lines of therapy was two.

At data cutoff, 14 of 32 patients had died, 13 due to disease progression and one due to the development of T-lymphoblastic lymphoma leukemia.

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