Histology-tailored neoadjuvant chemotherapy (HT) does not appear to be associated with better disease-free survival (DFS) or overall survival (OS) than standard anthracycline plus ifosfamide neoadjuvant chemotherapy (A+I) in 5 high-risk soft tissue sarcoma (STS) subtypes of the extremities or trunk wall, according to European researchers.
The final results from a randomized trial with Italian, Spanish, French, and Polish sarcoma groups has found A+I should remain the regimen of choice whenever neoadjuvant chemotherapy is considered across 5 histologic subtypes (high-grade myxoid liposarcoma [HG-MLPS], leiomyosarcoma [LMS], synovial sarcoma [SS], malignant peripheral nerve sheath tumor [MPNST], and undifferentiated pleomorphic sarcoma [UPS]).
In this randomized, open-label, phase 3 trial, all the patients had localized high-risk STS (grade 3; size, 5 cm or greater) of an extremity or trunk wall and were treated between May 2011 and May 2016. These 5 histologic subtypes account for 80% of all high-risk STS of the extremities or trunk wall. In this current investigation, 287 patients were randomly assigned in a 1:1 ratio to receive 3 cycles of A+I or HT. Among the 287 patients, 97.9% underwent surgery (281 individuals). The cohort included 177 men and 110 women (ClinicalTrials.gov Identifier: NCT01710176).
The HT regimens included trabectedin in patients with HG-MLPS and gemcitabine plus dacarbazine in patients with LMS. In patients with SS, the HT regimen was high-dose prolonged-infusion ifosfamide and in patients with MPNST, the HT regimen was etoposide plus ifosfamide. Patients with UPS received gemcitabine plus docetaxel as their HT regimen.
Among the 240 evaluable patients, there were no complete responses and nearly 10% had a partial response (23 individuals). The researchers found a non-statistically significant difference in 5-year DFS (0.55 vs 0.47, respectively) and a statistically significant difference in OS in favor of A+I (0.76 vs 0.66, respectively). The study showed no toxic deaths in either group.
Gronchi A, Palmerini E, Quagliuolo V, et al. Neoadjuvant Chemotherapy in high-risk soft tissue sarcomas: Final results of a randomized trial from Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups (published online May 18, 2020). J Clin Oncol. doi: 10.1200/JCO.19.03289