1730P - Preliminary results of phase II study on preoperative intensity-modulated radiotherapy with concurrent PARP inhibitor for patients with non-metastatic inoperable or borderline operable extremity and trunk soft tissue sarcoma

Background

We hypothesized that PARP inhibitor Fluzoparib and preoperative radiotherapy (RT) will transform inoperable or borderline operable soft tissue sarcoma (STS) into an operable disease without increase of major wound complications (MWCs).

Methods

Primary or recurrent non-metastatic unresectable or borderline resectable extremity or trunk STS was enrolled. Patients received preoperative moderately fractionated RT of 43.5Gy in 15 fractions with concurrent and sequential Fluzoparib (100mg Bid for 10 weeks in total), followed by wide resection. NCI-CTC 5.0, RECIST 1.1 criteria, and EORTC-STBSG criteria was used to evaluate acute toxicities, clinical and pathological response. The primary endpoint was defined as MWCs as per the SR2 criteria within 4 months post-surgery.

Results

From Jun 2023 to Apr 2024, 49 patients were enrolled and 46 completed RT. Forty-six tumours (93.9%) were evaluated as unresectable or borderline resectable, with 40 tumor (81.6%) adjacent to or encircling key structures. There were 40, 6 and 3 patients having full-dose Fluzoparib, drug dose reduction and RT alone, respectively. The observed ≥Grade 3 Fluzoparib-related or RT-related acute toxicity is anemia in 1 patient, and skin reaction in two patients. There're 8 (8/43, 18.6%), 11 (25.6%) and 24 patients (55.8%) who achieved PR, tumor reduction by 20% and SD as per RECIST 1.1 at 4-6 weeks post-radiotherapy, respectively. Till May, 2024, there were 40 patients who underwent non-R2 limb-conserving surgery, with 26 R0 and 14 R1 resection (margin less than 1mm). Thirteen out of 37 patients (35.1%) with at least 6 weeks follow-up had MWCs, with 12 in lower extremity (12/33, 36.4%). As per the EORTC criteria, there were 1 (1/38, 2.6%), 7 (18.4%) and 10 (26.3%) patients achieving pathological Grade B, C, and D remission. In all, 28 patients (73.7%) had higher than 10% of hyalinization/fibrosis.

Conclusions

For patients with non-metastatic extremity or trunk STS, the combination of PARP inhibitor and pre-operative moderately fractionated RT is safe and well-tolerated, and make majority of tumors transformed into operable disease.

Clinical trial identification

NCT05938374.

Editorial acknowledgement

Funding

CAMS Innovation Fund for Medical Sciences (CIFMS) [grant number 2023-I2M-C&T-B-089] and the Beijing Hope Run Special Fund of Cancer Foundation of China [grant number LC2020A15].

Disclosure

All authors have declared no conflicts of interest.