(P 190) DOES RESPONSE TO PRIOR CHEMOTHERAPY PREDICT OUTCOME FROM FURTHER SYSTEMIC TREATMENT IN ADVANCED LEIOMYOSARCOMA? A SINGLE UK CENTRE EXPERIENCE

Objective: Leiomyosarcoma is an aggressive soft tissue sarcoma subtype. The development of unresectable and/or metastatic disease is typically rapidly fatal. Cytotoxic chemotherapies remain the mainstay of palliative treatment but are associated with limited efficacy and significant toxicity, with the potential for adverse quality of life. The means for identifying patients most likely to gain benefit from consecutive lines of palliative chemotherapy are limited. We undertook to assess whether response to prior chemotherapy could be a useful factor in selecting patients most likely to benefit from further lines of systemic treatment.

Methods: We performed a retrospective review of outcomes for all patients treated with 2 or more lines of palliative systemic anti-cancer therapy (SACT) (excluding anti-oestrogen agents) for advanced leiomyosarcoma at a single UK sarcoma centre between 2004 and 2022. Eligible patients were identified from a prospectively maintained departmental database that included contemporaneous data on chemotherapy response and progression-free intervals. Baseline patient and tumour characteristics were recorded, as were outcomes for each line of palliative SACT. Comparison of progression-free survival following 1st (CT1) and 2nd line (CT2) SACT was performed, with analysis of PFS following CT2 stratified by response and 12 week progression-free state (12wPFS) after CT1.
We identified 61 patients who received at least 2 lines of palliative SACT for advanced leiomyosarcoma. 56/61 (92%) of patients were female. Average age at start of CT1 was 53.0 years (range 31.5-75.3). Primary leiomyosarcoma site was uterus in 48%, retroperitoneal 25%, abdominopelvic 15%, extremity 10% and unknown 3%. Tumour grade per FNLCC was grade 1,2 and 3 in 3%, 31% and 66% respectively. Organs involved by metastatic disease were lung 61%, liver 33%, peritoneum 13%, bone 15% and soft tissue 8%. ECOG performance status at start of CT1 was 0, 1, 2, 3 and not recorded in 31%, 54%, 5%, 2% and 8%.

Results: CT1 regimen was doxorubicin-based in 90% (85% monotherapy, 5% combination with ifosfamide), gemcitabine-docetaxel 8%, trabectedin 2%. Median PFS for CT1 was 142 days (95% CI 74-205). Best response to CT1 was partial response (PR) in 9/61 (15%), stable disease (SD) 24/61 (39%) and disease progression (PD) 25/61 (41%). Best response to CT1 was not evaluable in 3/61 (5%).

CT2 regimen was gemcitabine-docetaxel in 54%, ifosfamide 23%, doxorubicin 8%, trabectedin 8%, pazopanib 5% and carboplatin-paclitaxel in 2%. Median PFS for CT2 was 118.5 days (95% CI 70-169). Best response to CT2 was PR 10/61 (16%), stable disease 21/61 (34%) and disease progression 27/61 (34%). Best response to CT1 was not evaluable in 3/61 (5%).

There was no significant correlation observed between matched CT1 PFS and CT2 PFS (Pearson R = 0.02). When stratified by best response to CT1 (PR/SD vs PD), there was no significant difference in CT2 PFS (median PFS 140.5 days [95%CI 84-178) vs 76 days [95%CI 64-189]). Similarly, when stratified by CT1 12wPFS there was no significant difference in CT2 PFS between those who achieved CT1 12wPFS or not (median PFS 108 days [95%CI 63-169] v 122 days [95%CI 64-226]).

37/61 (61%) of patients had further lines of SACT (3rd-5th line). These regimens were trabectedin in 32/61 (52%), gemcitabine-docetaxel 8/61 (13%), pazopanib/axitinib/anlotinib 8/61 (13%), ifosfamide 1/61 (2%).

Efficacy outcomes for specific chemotherapy regimens regardless of line of treatment were as follows:
- doxorubicin-based (n=60): median PFS 142 days; best response - PR 15%, SD 42%, PD 42%, NE 2%
- gemcitabine-docetaxel (n=45): median PFS 157 days; best response – PR 22%, SD, 30%, PD 41%, NE 7%
- trabectedin (n=38): median PFS 101 days: best response – PR 8%, SD 39%, PD 47%, NE 5%
- ifosfamide (n=15): median PFS 70 days: best response – PR 13%, SD 27%, PD 60%

Conclusion: We found limited efficacy of palliative SACT in advanced leiomyosarcoma in our single centre cohort, with results consistent with the available published evidence base. Doxorubicin-based regimens and gemcitabine-docetaxel had similar efficacy outcomes in this series. Response and degree of benefit from 1st line SACT did not appear to predict for benefit from 2nd line SACT. These findings indicate that lack of benefit from first line chemotherapy should not be seen to disqualify patients with advanced leiomyosarcoma from proceeding with 2nd line treatment.