KEY TAKEAWAYS
- The AXAGIST phase 2 trial aimed to investigate the synergy of axitinib and avelumab in advanced GIST after standard therapy failure.
- The primary endpoint was to determine PFS.
- Researchers noted significant efficacy and long-term benefit from the axitinib-avelumab combination in pretreated GIST.
The development of tyrosine kinase inhibitors (TKIs) has significantly advanced the treatment of unresectable or metastatic gastrointestinal stromal tumors (GISTs), yet resistance mechanisms continue to drive disease progression.
Piotr Rutkowski and the team considered the potential immunomodulatory effects of VEGF inhibitors and hypothesized that combining VEGF and PD-L1 inhibitors could have a synergistic effect and improve therapeutic outcomes.
They performed an inclusive analysis of AXAGIST (NCT04258956), a 2-centre, single-arm, phase II, 2-stage trial evaluating the efficacy and safety of avelumab (10 mg/kg IV Q2W) combined with axitinib (5 mg PO BID) in patients with unresectable or metastatic GIST after the failure of standard therapy. The primary endpoint was progression-free survival (PFS) at 3 months according to RECIST 1.1 criteria. Secondary endpoints included overall survival (OS), overall response rate (ORR), and safety.
About 58 patients were enrolled, with 56 evaluable for safety and efficacy. The median age was 60 years (range 18-80); 21 patients (37.5%) were female, and 30 patients (53.6%) had received prior treatment with 3 lines of TKIs. The median follow-up was 27.4 months (95% CI, 25.4-NA). The best response included partial response in 5 patients (8.9%), stable disease in 34 patients (60.7%), and progressive disease in 17 patients (30.4%).
Among patients with partial response, the median duration of response was 18.5 months (95% CI, 18.3-NA). The PFS rate at 3 months was 57.1%. Median PFS and OS were 4.6 months (95% CI, 2.9-6.4) and 14.2 months (95% CI, 9.2-26.3), respectively.
The 12-month PFS and OS rates were 22.8% (95% CI: 14-37.1) and 59.3% (95% CI: 47.5-74), respectively. Adverse events (AEs) occurred in 94.6% of patients, with 30.4% experiencing grade 3 or higher AEs, all of which were manageable.
The study concluded that the combination of targeted therapy and immunotherapy demonstrated significant efficacy in pretreated patients with GIST. A substantial subset of patients achieved long-term clinical benefit, with further biomarker correlations to be presented.
The trial was sponsored by Maria Sklodowska-Curie National Research Institute of Oncology.
Source: https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/47
Clinical Trial: https://clinicaltrials.gov/study/NCT04258956
Rutkowski P, Klimczak A, Teterycz P, et al. (2024). “Axitinib plus avelumab in patients with unresectable/metastatic gastrointestinal stromal tumor (GIST) after failure of standard therapy: Single-arm phase II study (AXAGIST).” Presented at ESMO 2024 (Abstract 1723MO).
