(P 456) OUTCOMES OF FIRST-LINE CHEMOTHERAPY IN ADVANCED ADULT-TYPE RHABDOMYOSARCOMAS: POOLED ANALYSIS OF CLINICAL TRIALS FROM THE EORTC SOFT TISSUE AND BONE SARCOMA GROUP

Objective: Embryonal and alveolar rhabdomyosarcomas are uncommon in adults. Pleomorphic and spindle cell/sclerosing are the most frequent adult-type rhabdomyosarcomas (A-Rhab), both considered ultra-rare sarcomas. Data on chemosensitivity in A-Rhab remain scarce. We assessed outcomes of first-line chemotherapy (ChT) in A-Rhab patients (pts) enrolled in EORTC Soft Tissue and Bone Sarcoma Group trials.

Methods: Data from A-Rhab pts entered in prospective STS phase II/III trials after 1990 were pooled. Diagnosis was locally or centrally confirmed, and all pts had inoperable/metastatic disease at baseline. Response was assessed per RECIST 1.1. Progression-free survival (PFS) and overall survival (OS) were calculated from date of registration or randomization.

Results: Eight clinical trials were included, yielding a dataset of 35 pts with A-Rhab, of whom 19 (54.3%) were men. Median age at diagnosis was 38 years (range 18–71). Tumor grade was intermediate in 4 pts (11.4%), and high in 26 (74.3%). First-line ChT included anthracycline alone in 14 pts (40%), doxorubicin plus ifosfamide in 8 (22.8%), ifosfamide alone in 9 (25.7%), and other regimens in 4 (11.4%). Best response was 1 complete response (2.9%), 5 partial responses (14.3%), 12 stable disease (34.3%), and 14 progressive disease (40%). Median follow-up for pts alive (n=5) at the time of their respective study clinical cut-off dates was 7.2 m (IQR= 4.8 - 21.8). Global median PFS was 2.7 m (95% CI = 1.6-4.1): 3.4 m (95% CI: 0.8–5.0) for pts treated with anthracycline alone, 3.6 m (95% CI: 1.3–8.2) for those receiving doxorubicin plus ifosfamide, and 1.7 m (95% CI: 0.9–7.3) for those treated with ifosfamide alone. Global median OS was 8.5 m (95% CI = 6.2-12.3): 7.8 m (95% CI: 4.0–15.4) for anthracycline, 12.6 m (95% CI: 1.7–22) for combination of doxorubicin and ifosfamide, and 8.5 m (95% CI: 1.9–NE) for ifosfamide alone.

Conclusion: In this analysis, first-line ChT in A-Rhab pts yielded modest outcomes, with low response rates and limited PFS. Collaborative efforts are essential to better define treatment strategies and improve outcomes in these ultra-rare sarcoma subtypes.