High-Dose Ifosfamide for advanced thymic epithelial tumors (TETs): a TYME network study

Background: Patients (pts) with advanced thymoma (TM) and thymic carcinoma (TC) progressing to standard, platinum-based chemotherapy, have limited and poorly active treatment options. Referral centers of the Italian Collaborative Group for ThYmic MalignanciEs (TYME) network prospectively evaluated activity of highdose ifosfamide in this subset of patients Methods: We performed a prospective muliticenter study in pts with advanced TETs, progressing at least to one line of platinum-based chemotherapy. Pts received Ifosfamide (1g/m2 /day) and sodium-2-mercaptoethanesulfonate (1g/m2 /day), as continuous infusion, via a portable pumps for 14 consecutive days. Treatment was administered every 4 weeks until progression or unacceptable toxicity, up to a maximum of 6 cycles. The primary endpoint of the study was the overall response rate (ORR) by RECIST 1.1. The secondary endpoint was Progression Free Survival (PFS). All CT scans were revised by a referral center radiologist. Results: 17 pts (12 TC/ 5 TM; 8 stage IVA/ 9 stage IVB, 6 females/ 11 males) were enrolled from October 2020. Median age was 60 years (range 35-82). All patients had RECIST tumor progression at the time of study entry. The median number of previous systemic treatment was 2 (range 1-5). Eleven pts were pretreated with an immune checkpoint inhibitor (ICI) and 12 pts with an anti-angiogenic drug. All pts were evaluable for response: ORR was 23.5% (95%CI, 6.8% - 49.9%; 4/17) and disease control rate was 70.6% (95%CI, 44.0%- 89.7%; 12/17). Among the 12 pts with TC, 2 reached a partial response (PR), 5 stable disease (SD) and 5 had a progressive disease (PD) as best response; among the 5 pts with TM, 2 PR and 3 SD were observed. In the whole patients’ cohort, the mean best tumor shrinkage from baseline was +6.8%, ranging from a mean value of +13.9% in TC and -12.8% for pts with TM. The median PFS for all pts was 4.5 months (95%CI 4.0-6.5): 4.1 mo. (95%CI, 3.4-6.4) for pts with TC and 6.55 mo. (4.2-NA) for those with TM. Conclusions: preliminary results showed antitumor activity of ifosfamide in pts with tets. Recruitment is currently ongoing.