In a Japanese phase II trial (MARBLE) reported in The Lancet Oncology, Shukuya et al found that atezolizumab plus carboplatin/paclitaxel showed promising results in patients with recurrent or metastatic thymic carcinoma.
Study Details
In the multicenter trial, 48 patients enrolled between June 2022 and July 2023 were treated with atezolizumab at 1,200 mg, carboplatin area under the curve (AUC) = 6, and paclitaxel at 200 mg/m² every 3 weeks for up to six cycles, followed by atezolizumab at 1,200 mg every 3 weeks for up to 2 years or until progression or unacceptable toxicity. The primary endpoint was objective response rate based on independent central review. Based on objective response rate in previous trials of platinum-based chemotherapy for chemotherapy-naive advanced thymic carcinoma, it was hypothesized that an objective response rate of 30% would constitute a clinically meaningful threshold.
Key Findings
Median follow-up was 15.3 months (interquartile range = 13.8–16.6 months). Objective responses (all partial) were observed in 27 of 48 patients (56%, 95% confidence interval [CI] = 41%–71%) , exceeding the clinically meaningful threshold of 30% (P < .0001). Median duration of response was 6.4 months (95% CI = 4.1 months to not estimable). An additional 20 patients (42%) had stable disease as best outcome. Median progression-free survival was 9.6 months (95% CI = 7.7–14.8 months. Median overall survival was not reached (95% CI = 19.2 months to not estimable).
The most common grade ≥ 3 adverse events were neutropenia (56%), leukopenia (33%), febrile neutropenia (23%), and maculopapular rash (13%). The most common grade 3 to 4 immune-related averse events were severe skin disorders (17%) and liver dysfunction or hepatitis (8%). No treatment-related deaths were observed.
The investigators concluded “In previously untreated advanced thymic carcinoma, the addition of atezolizumab to carboplatin and paclitaxel conferred clinically meaningful antitumour activity with a manageable safety profile. Thus, atezolizumab plus carboplatin and paclitaxel might become a viable treatment option for previously untreated advanced or recurrent thymic carcinoma.”
Takehito Shukuya, MD, of Juntendo University Graduate School of Medicine, Tokyo, is the corresponding author for The Lancet Oncology article.
Disclosures: The study was funded by Chugai Pharmaceutical. For full disclosures of all study authors, visit thelancet.com.
