(P 431) REAL-WORLD EXPERIENCE OF EFFICACY AND TOLERABILITY OF CONTINUOS INFUSION IFOSFAMIDE AMONG ADVANCED SOFT TISSUE AND BONE SARCOMAS PATIENTS: A SINGLE CENTRE RETROSPECTIVE COHORT.

Objective: In advanced or metastatic Soft Tissue (STSs) and Bone Sarcomas (BSs), selecting second or further-line therapies generally hinges on histotype, patient performance status and toxicity profile, given the absence of treatment sequences guidelines. Our analysis reports a sarcoma-referral center experience on continuous infusion Ifosfamide (ciIFO), in advanced STS and BS patients in order to assess the response rate (RR) and the toxicity profile.

Methods: We retrospectively collected clinical data of STSs and BSs -osteosarcoma and chondrosarcoma- patients treated with ciIFO at our Institute from January 2013 to April 2023. The study included patients’ demographic characteristics, pathological details, treatment history, response rates (RR), and toxicities per CTCAE Criteria v.5.

Results: Ninety-eight patients were included in the final analysis, with a female:male ratio of 42:56 and a median age of 49 years (15-81). The most common histotypes were liposarcoma (26%), small round cell sarcomas (Ewing Sarcomas, DSRCT, rabdomiosarcomas) (14%) and BSs (13%), the most common sites were extremities (39%) and retroperitoneum (21%). At the start of ciIFO, 60/98 (61%) patients had previously received IFO combined to doxorubicin in a perioperative setting or as first-line treatment for metastatic disease. Thirteen/98 (13%) patients had only one kidney due to en-bloc resection of the primary retroperitoneal disease.
The median follow-up was 37.8 months (0.4-100.2). Most of patients, 49/98 (50%), received ciIFO as second-line treatment, 20/98 (20%) as first and 29/98 (30%) ≥ third-line.
RR was evaluable in 91 patients, showing a Disease Control Rate (DCR) of 34% (31/91), including partial responses (PR) in 10% (9/91) and stable disease in 24% (22/91). Synovial Sarcomas and BSs had the best DCR (60% and 50% respectively) (Table 1). Patients previously treated with ciIFO had a trend to a better DCR vs IFO-naïve group (39% vs 26%), with no differences by ciIFO line of treatment. No significant differences in RR were observed by sex, although female had a slightly higher incidence in PR.
The median Progression Free Survival (mPFS) was 3.0 months (2.7–3.8) and the median Overall Survival (mOS) was 11.2 months (8.0–16.1). Females had slightly better mOS compared to males (15.1 vs. 8.8 months) (Figure 1) while no differences were reported in terms of mPFS.
We observed a better mOS for ciIFO as second-line treatment: mOS was 15.6 months (7.0–24.6) for second-line ciIFO vs 9.7 months (5.7–19.2) for first-line and 10.1 months (5.7–20.4) for later-lines, while mPFS was quite similar by line. No significant differences in outcomes by histotypes were observed (Figure 2). ciIFO was generally well tolerated, with an 11% discontinuation rate and no severe renal toxicity.

Conclusion: The present study, focused on the role of ciIFO on advanced or metastatic STS and BS patients, highlights at least two crucial points that warrant prospective analyses. Firstly, ciIFO showed a quite interesting activity even in patients previously treated with IFO-based regimens, achieving a DCR of 34% in a population that included some heavily pretreated patients. As expected Synovial Sarcoma and BS patients appear to benefit the most in terms of RR, that is particularly important when tumor shrinkage is needed to improve symptoms. The better outcomes reported for second-line ciIFO compare to first-line may be explained by a higher frailty of the cohort where the combined regimen was excluded. Second, unlike other IFO-based regimens, ciIFO appears to be better tolerated, even in pretreated frail patients (18% of population had a ≥2 ECOG PS) and in a post-operative monokidney setting, supporting how this condition did not affect the ciIFO toxicity profile.