In the Italian phase II CAVEATT trial reported in The Lancet Oncology, Conforti et al found that the combination of avelumab and axitinib was active in patients with unresectable or metastatic type B3 thymomas and thymic carcinomas who experienced disease progression after platinum-based chemotherapy.

In the study, 32 patients from two centers (European Institute of Oncology and the Humanitas Institute, Milan) enrolled between April 2019 and June 2021 received avelumab at 10 mg/kg every 2 weeks and axitinib at 5 mg twice daily until disease progression or unacceptable toxicity. Of the 32 patients, 27 had thymic carcinoma, 3 had type B3 thymoma, and 2 had mixed-type B3 thymoma and thymic carcinoma; 29 had stage IVB disease; and 13 (41%) had received prior treatment with an antiangiogenesis agent. Prior treatment with immune checkpoint inhibitors was not permitted. The primary endpoint was centrally assessed overall response rate.

Responses

Objective responses (all partial) were observed in 11 patients (34%, 90% confidence interval [CI] = 21%–50%). An additional 18 patients (56%) had stable disease; the disease control rate was 91%. The median duration of response was 5.5 months (90% CI = 3.9–9.2 months). After a median follow-up of 22.4 months, median progression-free survival was 7.5 months (90% CI = 3.7–10.0 months), with 6- and 12-month rates of 61.3% and 29.0%. At data cutoff, median overall survival was 26.6 months (90% CI = 17.0–30.0 months), with 12- and 24-month rates of 82.7% and 52.2%.   

Among 19 patients who had not received prior antiangiogenesis treatment, the objective response rate was 47%, compared with 15% in the 13 patients who had received prior treatment. Median progression-free survival was 10.0 vs 4.5 months, and median overall survival was 26.6 vs 17.0 months. The objective response rate among the 27 patients with thymic carcinoma alone was 33%, with two responses observed in the remaining 5 patients.

Adverse Events

The most common treatment-related grade 1 or 2 adverse events were diarrhea (57%); hypertension (34%); and nausea, fatigue, and abdominal pain (31% each). The most common treatment-related grade 3 or 4 adverse events were hypertension (19%) and increased creatine kinase (9%). Serious new-onset immune-related adverse events occurred in four patients (12%), consisting of grade 3 interstitial pneumonitis in one, grade 3 polymyositis in two, and grade 4 polymyositis in one. No treatment-related deaths occurred.  

The investigators concluded, “Avelumab combined with axitinib has promising antitumor 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.”

Fabio Conforti, MD, of the Division of Melanoma, Sarcoma, and Rare Tumors, European Institute of Oncology, IRCCS, Milan, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Pfizer. For full disclosures of the study authors, visit thelancet.com.