KEY TAKEAWAYS
- The RELEVANT phase II trial aimed to evaluate the effectiveness and safety of R combined with CBDCA and PTX as first-line therapy for advanced TC.
- The primary endpoint was ORR. Secondary endpoints were DCR, PFS, OS, and safety.
- The result demonstrated that adding R to first-line CBDCA and PTX for advanced TC showed promising activity and safety in a small, rare disease study, warranting further investigation.
Thymic carcinoma (TC) is a rare and aggressive tumor that responds poorly to treatment. In advanced stages, antiangiogenic drugs have demonstrated effectiveness in TC. Ramucirumab (R), a monoclonal antibody inhibiting VEGF2, is already approved for various solid tumors.
For this study, researchers aimed to evaluate the effectiveness and safety of R combined with carboplatin(CBDCA) and paclitaxel (PTX) as first-line therapy for advanced TC. They enrolled treatment-naive patients with advanced TC following centrally reviewed pathology diagnoses.
All participants received 10 mg/kg of R, CBDCA with an AUC of 5, and PTX at 200 mg/m2 on day 1 every 21 days for 6 cycles. Maintenance therapy with R at 10 mg/kg continued until disease progression or intolerable toxicity.
Researchers employed a Green-Dahlberg 2-stage design, analyzing 30 patients in the first stage with a null hypothesis of a 20% objective response rate (ORR). If at least 5 responses were observed, 25 patients could be included in the second stage.
The primary endpoint was ORR; secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Centralized radiologic review was conducted.
Of 52 screened individuals, 37 with a median age of 60.5 years were enrolled. Most were male (70.3%), and (86.5%) had stage IVB disease. Regarding performance status, (70%) had an ECOG PS of 0.
The first-stage assessment, conducted by investigators, revealed an 80% ORR [95%CI 63.1-91.6] and a 100% DCR [95%CI 90-100]. In the centralized radiological review (33/35 evaluable), the ORR was 57.6% [95%CI 39.2-74.5], with 57.6% achieving a partial response (PR) and 42.4% stable disease (SD); DCR was 100% [95%CI 89-100].
After a median follow-up of 31.6 months [21.6-40.5], median progression-free survival (mPFS) was 18.1 months [95%CI 10.5-52.3], and median overall survival (mOS) was 43.8 months [95%CI 22.5-NE]. Among 35 patients, 80% experienced at least one treatment-related adverse event (TRAE), with 45.7% being Grade 3 or higher (hypertension 8.8% and neutropenia 20% were the most common).
The result demonstrated that adding R to first-line CBDCA and PTX for advanced TC showed promising activity and safety in a small, rare disease study, warranting further investigation.
Clinical Trial: https://clinicaltrials.gov/study/NCT03921671
Proto C, Manglaviti S, Galli G, et al. Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial. Ann Oncol. 2023;34(suppl_2):S1254-S1335. doi:10.1016/annonc/annonc1358.
