(P 180) HEALTH RELATED QUALITY OF LIFE OF PATIENTS WITH ADVANCED LEIOMYOSARCOMA AND OTHER SOFT TISSUE SARCOMAS TREATED WITH CABOZANTINIB AND TEMOZOLOMIDE

Objective: Oral combination strategies are increasingly being studied in management of advanced soft tissue sarcomas but may be associated with increased toxicities. Patient reported outcomes (PROs) provide necessary information on toxicities of a given regimen from a patient perspective and help guide management. Cabozantinib (CAB), an oral tyrosine kinase inhibitor targeting dual VEGF and c-MET pathways was combined with temozolomide (TMZ), an alkylating agent in a Phase II trial in patients with advanced leiomyosarcoma (cohort 1) and other soft tissue sarcomas (cohort 2) which showed improvement in PFR at 12 weeks > 39%. Pooled PRO data across cohorts was collected at scheduled time points during the study and are reported.

Methods: Across 5 sites included in the Midwest Sarcoma Trials Partnership a total of 72 patients were enrolled (42 in cohort 1 and 30 in cohort 2). Inclusion criteria included age ≥ 18, adequate performance status (ECOG 0-1), organ function, measurable disease (RECIST 1.1), and 0-5 prior chemotherapy regimens. CAB 40 mg PO daily plus TMZ 150-200 mg/m2 PO 1-5 days were given in 28-day cycles until disease progression or unacceptable toxicity. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30, which is scored 0-100) at baseline during screening and then on Day 1 of every cycle prior to the study treatment administration, and at the end of treatment. A linear mixed effects model was used to assess EORTC QLQ-C30 trends over time. Trends were assessed from baseline to Cycle 3 (~ 12 weeks). The analyses were performed for the following covariates: response group (responders and non-responders), age group ( < 40, 40-60, and >60 years), and gender (female and male). An interaction term of the covariates with time was included in the model to explore if the longitudinal trajectories differed by levels of the covariates. P-values < .05 were considered statistically significant and all tests were 2-sided. Data management and statistical analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) and R version 4.3.0 (R Foundation for Statistical Computing).

Results: 63/72 (88%) patients completed a baseline QOL survey and 43 (60%) patients completed the QOL survey at all predefined points up to cycle 3 in the study. ECOG performance score of 0 was present in 37/63 (59%) and 26/43 (60%), respectively. 6/63 patients had a partial response as per RECIST 1.1 criteria and all 6 responders were included in the 43 patient subset as well. While baseline ECOG 0 percentage was slightly higher in responders (67% vs 58%, p=NS), at baseline, responders had higher mean QLQ-C30 scores of physical functioning (92.8 vs 79.6, p =0.003), role functioning (94.4 vs 76.0 p=0.020) and global health status score (80.6 vs 69.0, p=0.001). Appetite loss (5.6 vs 22.2, p=0.033) and financial problems (5.6 vs 22.8, p=0.029) were reduced in responders when compared to non-responders. When restricted to the 43 patients with 3-cycles of QOL data, Overall the estimated EORTC QLQ-C30 symptom scores for diarrhea, nausea/vomiting, fatigue and appetite loss were reported to increase over time but there was no significant interaction effect based on clinical response, age groups or gender. Constipation symptoms did not statistically change over time.

Conclusion: Patients with advanced leiomyosarcoma and soft tissue sarcoma with higher baseline QLQ-C30 scores of physical functioning, role functioning, global health status scores and less appetite loss or financial problems during treatment with CAB + TMZ had better clinical responses. Diarrhea and nausea/vomiting worsened over the first 3 cycles, suggesting management during the course of treatment may need to intensify. Fatigue and appetite loss also worsened. The reported symptoms are commonly seen with use of either drug hence may need careful monitoring and management of toxicities to best treat patients with this regimen.