Soft Tissue Sarcoma Patients Do Not Benefit From Histology-Tailored Neoadjuvant Chemotherapy

Author: By Laura Cowen, medwireNews Reporter 

medwireNews: Histology-tailored (HT) neoadjuvant chemotherapy does not prolong disease-free survival (DFS) in patients with high-risk soft tissue sarcoma (STS) of an extremity or the trunk wall relative to anthracycline plus ifosfamide, and may be associated with lower overall survival (OS), researchers report. 

This suggests “that [anthracycline plus ifosfamide] should remain the regimen to choose whenever neoadjuvant chemotherapy is used in patients with high-risk STS”, write Alessandro Gronchi, from Istituto Nazionale dei Tumori in Milan, Italy, and co-authors in the Journal of Clinical Oncology. 

The phase III study was a collaboration involving Italian, Spanish, French and Polish Sarcoma Groups. Between 2011 and 2016, 287 patients (mean age 40 years, 62% men) with localised high-risk STS (grade 3; ≥5 cm) were randomly assigned to receive three cycles of HT neoadjuvant chemotherapy (n=142) or anthracycline plus ifosfamide (n=145).  

The HT regimens consisted of trabectedin for high-grade myxoid liposarcoma (n=28), gemcitabine plus dacarbazine for leiomyosarcoma (n=16), high-dose prolonged-infusion ifosfamide for synovial sarcoma (n=34), etoposide plus ifosfamide for malignant peripheral nerve sheath tumour (n=12) and gemcitabine plus docetaxel for undifferentiated pleomorphic sarcoma (n=50). 

The researchers report that, in May 2016, the study was terminated early following a third prespecified interim futility analysis, which showed that at a median follow-up of 1 year, individuals in the HT arm had double the risk for relapse and nearly three times the risk for death compared with those in the anthracycline plus ifosfamide arm. 

Nonetheless, the final analysis went ahead as planned, but with modified statistical analyses that used a two-sided hypothesis rather than a one-sided superiority approach. 

This analysis revealed that, after a median 52 months of follow-up, the projected 5-year DFS rates did not differ significantly between the patients who received HT neoadjuvant chemotherapy and those who received anthracycline plus ifosfamide, at 47.4% and 54.6%, respectively. 

During follow-up there were 45 deaths in the HT group and 28 in the anthracycline plus ifosfamide group and estimated 5-year OS was significantly lower with the former versus latter treatment, at 65.9% versus 75.7%. The resulting hazard ratio for death was 1.77 in favour of anthracycline plus ifosfamide. 

“In the end, this trial shows that anthracyclines are still an important component of chemotherapy of STS in the eligible histologic subtypes”, Alessandro Gronchi et al write. 

However, they add that they “would not conclude that any HT was proven inferior”, because HT regimens could also include an anthracycline. 

Reference 

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. J Clin Oncol; Advance online publication 18 May 2020. doi:10.1200/JCO.19.03289