Dr Rutkowski on Avelumab Plus Axitinib in Unresectable/Metastatic GIST

Piotr Rutkowski, MD, professor, Surgical Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, discusses findings from the phase 2 AXAGIST trial (NCT04258956), a single arm study of avelumab (Bavencio) in combination with axitinib (Inlyta) in patients with unresectable/metastatic gastrointestinal stromal tumor (GIST) who had progressed on standard therapy.

For patients who have progressed following treatment with imatinib (Gleevec), therapeutic options are typically limited, and adding more than a traditional TKI is often desired, Rutkowski begins. Axitinib, known for its antiangiogenic properties, also exerts an immunomodulatory effect, according to Rutkowski. This drug acts on KIT and PDGFR α/β, with an additional effect on VEGFR, making it a suitable candidate for combination therapy with avelumab, an anti–PD-L1 drug, he explains.

The rationale for combining these agents stems from evidence that this combination has been safe and effective in other cancer types, such as renal cell carcinoma, Rutkowski explains. Patients eligible for AXAGIST must have experienced disease progression within 3 months prior to enrollment, have had an ECOG performance status of 2 or lower, and have received prior therapy with imatinib and sunitinib (Sutent), without prior treatment with axitinib or avelumab. In this trial, the maximum treatment duration was 2 years, and the primary end point was theprogression-free survival (PFS) rate at 3 months. The 3-month PFS rate in evaluable patients (n = 56) was 57.1%, and the median PFS was 4.6 months (95% CI, 2.9-6.4). Additionally, the disease control rate was 69.6%, a significant outcome for this heavily pretreated patient population, he reports.

Importantly, the median overall survival (OS) was 14.2 months (95% CI, 9.2-26.3), which is particularly notable in patients who have undergone multiple prior lines of treatment, Rutkowski expands. At 12 months, 59.3% of patients were still alive, indicating promising long-term benefits with the combination, he emphasizes. Overall, the combination of avelumab and axitinib appears to be a highly promising therapeutic option for the third- or fourth-line management of GIST, he says. These findings indicate that this combination could represent a valuable treatment strategy for patients who have exhausted other options, Rutkowski concludes.