KEY TAKEAWAYS
- Avelumab with HT-RT is a phase I trial that evaluated the safety, tolerability, and effectiveness of avelumab in individuals diagnosed with mSTS.
- Patients with mSTS were treated with avelumab with HT-RT considering the primary endpoint as safety, and secondary endpoints included a local control rate at 3 months.
- Results demonstrated no DLTs or treatment-related deaths were observed, and the 3-month local control rate was 50%.
- These findings showed promising anti-tumor activity in mSTS patients.
Combining HT-RT (hypofractionated radiotherapy) with anti-PD-L1 therapy can improve local and distant tumor control in patients with metastatic soft tissue sarcoma (mSTS). This study evaluated the safety, tolerability, and effectiveness of avelumab with HT-RT in individuals diagnosed with mSTS.
The study was conducted between October 2018 and April 2022 and included patients who were above 18 years, had at least 2 pulmonary metastases, and had an ECOG performance status of 0-1. They received HT-RT (36 Gy in 12 fractions) and intravenous avelumab (10 mg/kg every 14 days) until disease progression. The primary endpoint was to assess the safety of avelumab with HT-RT. Secondary endpoints included evaluating the local control rate at 3 months and dose-limiting toxicities (DLT) during treatment with avelumab and HT-RT up to Cycle 7. Response to the treatment was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST).
About 12 patients with lung metastases were treated with avelumab and radiotherapy. The median age was 57.5 years (37-68), with 58% female patients. Histological subtypes included leiomyosarcoma (n = 2), undifferentiated pleomorphic sarcoma (n = 2), and spindle cell sarcoma (n = 2). Out of the 12 patients, 1 had previously received SBRT to the lung, and 5 (42%) had undergone prior systemic treatment. All patients received at least one cycle of avelumab, with a median of 9 cycles (range: 1-37). Treatment was discontinued in 11 (92%) patients, primarily due to progressive disease (83%). One patient stopped due to G4 immune-mediated hepatitis after the DLT period, and one continued on compassionate-use avelumab. Radiotherapy was completed by 92% of the patients (36 Gy, 12 fractions). There were no observed DLTs or treatment-related deaths. Acute HT-RT toxicity included 3 G2 cases (1 oesophagitis, 2 skin) noted up to 11 weeks. Late toxicities included 13 G1 cases (5 pneumonitis, 5 skin, 1 cardiac, 1 myelitis, 1 oesophagitis). Avelumab toxicities included 2 G3 cases (1 ALT rise, 1 viral infection) and 3 G4 cases (1 AST rise, 1 hepatitis, 1 sepsis) reported after the DLT observation period.
The median follow-up duration was 21.8 months (range: 3.2-31.9). The 3-month local control rate was 50% (95% CI, 21%-74%). At 3 months, RECIST responses were 0 complete response, 1 (8%) partial response, 5 (42%) stable disease, and 5 (42%) progressive disease
The study concluded that avelumab with HT-RT showed promising anti-tumor activity in patients with mSTS. Further studies are being conducted to assess the role of molecular biomarkers.
Source: https://meetings.asco.org/abstracts-presentations/220618
Clinical Trial: https://www.clinicaltrials.gov/study/NCT03602833
Shane H Zaidi, Nicos Fotiadis, Yolanda Augustin, Andrea Napolitano, Caitriona Goggin, Bernice Asare, Elizabeth Barquin, Steven Edmunds, Khin Thway, Charlotte Benson, Robin L Jones, and Aisha B Miah
Journal of Clinical Oncology 2023 41:16_suppl, 11552-11552
