Maintenance Regorafenib in Advanced Soft-Tissue Sarcoma Delays Progression
A phase 2 study showed that giving maintenance regorafenib could delay disease progression in patients with non-adipocytic soft tissue sarcomas.
Developing in connective tissues like bones and muscles, these spindle-shaped sarcoma cells are known for their aggressiveness and rapid spread: © BEST - stock.adobe.com
Maintenance therapy with regorafenib (Stivarga) prolonged progression-free survival (PFS) compared with placebo in patients with advanced non-adipocytic soft tissue sarcomas (NASTS) following first-line treatment, according to results from the phase 2 EREMISS trial (NCT03793361), published in Annals of Oncology.
When assessed by blinded central review, median PFS was 5.6 months in the regorafenib arm vs 3.5 months with placebo (HR, 0.53; 95% CI, 0.36-0.78; P= 0.001), representing an average PFS gain of 2.81 months (95% CI, 0.81-4.82; P= .006). Investigator-assessed PFS also favored regorafenib, with a median of 6.8 months compared with 3.6 months for placebo (HR, 0.59; 95% CI, 0.40-0.85; P= .005).
Although median overall survival (OS) was numerically longer in the regorafenib group (27.6 months vs 20.5 months; HR, 0.78; 95% CI, 0.50-1.22; P= 0.28), the difference was not statistically significant, and the study was not powered to detect OS benefits.
A total of 126 patients with NASTS were enrolled and randomly assigned to receive either 120 mg regorafenib on a 3 weeks on, 1 week off schedule (n = 65) vs placebo (n = 62) after receiving 6 cycles of doxorubicin-based chemotherapy as first-line treatment for advanced disease.
The primary end point was PFS, defined as the time between randomization and first disease progression, based on central radiological review using RECIST 1.1 criteria, or death from any cause. Secondary efficacy end points included the best tumor response during maintenance therapy, OS, and the time to start a subsequent line of systemic anticancer therapy, considering death as competing event.
Overall, the study enrolled 69 women (54.8%). The median age was 58 years (range, 18-85). The most common histological subtypes were: leiomyosarcomas (58.7%), undifferentiated pleomorphic sarcomas (11.9%), and malignant solitary fibrous tumors (6.3%). At study entry, 10 (7.9%) patients had locally advanced sarcoma without metastasis. The vast majority of patients had metastatic disease (92.1%) with bulky disease, including lung (67.5%), liver (34.9%) or bone metastases (26.2%).
Safety data showed that 87% of patients experienced at least 1 adverse event (AE), but no grade 5 AEs were reported. In the treatment arm, the majority of patients had grade 2 (32.8%) and grade 3 (54.7%) AEs. In the placebo arm, the majority of patients had grade 1 (43.5%) and grade 2 (29.0%) AEs. The most common grade 3 or greater clinical AEs in the regorafenib arm were fatigue (9.4%), hypertension (7.8%), and rash (7.8%). In the regorafenib arm, 28.1% of patients discontinued treatment because of toxicity.
For most patients with advanced NASTS, delaying progression while preserving quality of life remains a key treatment goal. Although doxorubicin-based chemotherapy remains the frontline standard, maintenance strategies such as regorafenib could offer meaningful clinical benefits.
The limitations associated with the current study include its small sample size, insufficient power to evaluate OS, and lack of quality of life measures. The investigators concluded that the study met its primary end point and shows an improvement in PFS in patients with NASTS, which led to a delay in starting further systemic treatment.
