Outcomes of patients with metastatic solid cancers treated on early phase clinical trials in western Australia.
Authors: Ab Rahman Ahmad Sufian , Hakeem Mohammad Usman , Abass Randa , Wainman Laura , Miller Jake , Abed Afaf , Humphries Timothy Guy , Meniawy Tarek , Shinde Rajiv , Lau Peter Kar Han , Bowyer Samantha , Millward Michael 
Published: June 2024

e23094

Background: Cancer drug development is flourishing with novel immunotherapy combinations, antibody drug conjugates and increasingly molecularly targeted therapies that have pushed the inclusion of phase I clinical trials into earlier lines of systemic treatment. Linear Clinical Research is a dedicated Phase I centre with a catchment area of over 3 million people. We conducted a retrospective review into the outcomes of our centre. Methods: We included patients between 01/01/2020 to 30/04/2023, with advanced/metastatic or rare cancers with no available or suitable standard of care treatment. Data were extracted from our internal database with minimum follow up of 6 months. The primary endpoint was overall survival (OS). Other endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), duration of treatment (DOT), post-treatment survival (PTS), and 90-day mortality. Subgroup analyses based on treatment type were performed. Multivariate cox regression analysis was performed as part of tertiary endpoints. Results: 251 patients were recruited to 53 trials. Median age : 61 years (range: 21-83 years), 54.6% female, 74.1% Caucasian, ECOG 0-1: 90.8%, 26.7% rare cancers, 52.2% had 0-1 line of previous treatment, 47.8% had ≥ 2 lines. Trial treatments were: 51.4% immunotherapy (IO), 30.7% targeted therapy matched to molecular findings (TT), 2.8% antibody drug conjugate (ADC), 12.7% combination therapy (IO/TT/ADC/chemotherapy), 2.0% endocrine therapy alone, and < 1% chemotherapy. At data cut-off, 129 OS events had occurred (56.0%, median follow up of 22.0 months).The median OS was 16.0 months (95% CI 11.1 - 20.9), median PFS: 3.0 months (95% CI 2.2 - 3.8), ORR: 23.6%, DCR: 67.3%, median TTR: 2.0 months (IQR: 1.0-3.0), median DOR: 14.0 months (IQR: 6.0-38.0), median DOT: 3.0 months (IQR 1.0-10.0), median PTS: 7.0 months (IQR 2.0-27.0), 90-day mortality: 17.7%. Median OS based on treatment type: 11.0 months (95% CI 5.7-16.3) (IO), 12.0 months (95% CI 1.6-22.4) (TT), median not reached (range :1.0-28.0) (ADC), and 19.0 months (95% CI 13.6-24.4) (combination therapy). Median PFS based on treatment type: 2.0 months (95% CI 1.2-2.8) (IO), 5.0 months (95% CI 2.5-7.5) (TT), 10.0 months (95% CI: 0.0-28.0) (ADC), 6.0 months (95% CI 2.2 - 9.8) (combination therapy). Multivariate Cox analysis showed that higher number of lines of previous treatment was negatively associated with PFS and OS when adjusted for age, gender, type of treatment, and baseline sum of diameter (SOD). Conclusions: Our overall OS, ORR, and DCR are better than historical data of phase 1 during chemotherapy era , and are comparable to other centers nationally and internationally. Further work needs to be done to improve survival outcomes including algorithms to better match patients and trials earlier in their disease course.