In the phase II TRASTS study reported in JAMA Oncology, Sanfilippo et al found that neoadjuvant trabectedin and radiotherapy did not meet the target objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) in patients with myxoid liposarcoma but did exhibit activity according to pathologic responses.
Study Details
In the study, 46 patients with localized resectable myxoid liposarcoma arising from an extremity or trunk wall were enrolled at sites in Spain, Italy, and France between July 2016 and September 2019. Treatment consisted of trabectedin at 1.5 mg/m2 via intravenous infusion over 24 hours every 21 days for a total of three cycles. Radiotherapy was started after the completion of the first trabectedin infusion (cycle 1, day 2) and given at 45 Gy in 25 fractions. Surgery was planned 3 to 4 weeks after administration of the last cycle and not until 4 weeks after the end of radiotherapy. The primary outcome measure was objective response rate on central review using RECIST criteria, with a goal of ≥ 70%.
Key Findings
Objective responses (all partial) were observed in 9 (22%) of 41 evaluable patients. An additional 32 patients (78%) had stable disease, and no patients had progressive disease.
Among 39 patients evaluable for centralized assessment of pathologic response, 5 (13%) had complete pathologic response. Median viable residual tumor was 10%, with 20 (51%) of 39 patients having ≤ 10% viable residual tumor and 33 (85%) having < 50% viable residual tumor.
At a median follow-up of 37 months (range = 16–62 months), no patients died and 7 (17%) of 42 evaluable patients had disease recurrence. Median time to recurrence was 15 months (range = 8–51 months); local recurrence was observed in one patient, and distant metastasis was seen in six. At 4 years, overall survival was 100% and disease-free survival was 84% (95% confidence interval = 73%–96%).
Major grade 3 or 4 adverse events among all 46 patients were neutropenia (26%), increased alanine aminotransferase (22%), increased aspartate aminotransferase (13%), increased gamma-glutamyl transferase (11%), leukopenia (4%), and anemia (2%). No treatment-related deaths occurred.
The investigators concluded, “Although the primary endpoint of this phase II nonrandomized clinical trial was not met ([RECIST] response in ≥ 70% of patients), results suggest this combination was well tolerated and effective in terms of pathologic response. Thus, trabectedin plus radiotherapy might be a treatment option regarding tolerability; further evidence should be generated in this setting.”
Roberta Sanfilippo, MD, and Alessandro Gronchi, MD, both of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, are the corresponding authors for the JAMA Oncology article.
Disclosure: The study was supported by National Cooperative Sarcoma groups. For full disclosures of the study authors, visit jamanetwork.com.
