Dr Rutkowski on the Safety Profile of Avelumab Plus Axitinib in GIST

Piotr Rutkowski, MD, professor, Surgical Oncology, Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland, discusses the safety findings and clinical implications from the phase 2 AXAGIST trial (NCT04258956), which evaluated avelumab (Bavencio) in combination with axitinib (Inlyta) in patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) who progressed on standard therapies.

Rutkowski explains that no new safety signals were identified in the AXAGIST trial. The majority of patients experienced adverse events (AEs), but most were grade 1 or 2 and were manageable. Rutkowski notes that immune-related AEs, commonly associated with PD-L1 inhibitors like avelumab, were mainly related to thyroid dysfunction. These events were manageable with standard interventions.

Notably, the safety profile of the avelumab and axitinib combination was consistent with that observed in previous studies, such as the phase 3 JAVELIN Renal 101 trial (NCT02684006). In this trial, avelumab plus axitinib also demonstrated a significantly longer progression-free survival (PFS) with avelumab plus axitinib than with sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC) regardless of PD-L1 expression.

The AXAGIST trial enrolled a heavily pretreated population of patients with GIST who progressed on standard therapies, including TKIs such as imatinib (Gleevec) and sunitinib (Sutent). Although not all TKIs have been fully explored in this setting, the combination of axitinib, with its antiangiogenic and immunomodulatory effects, and avelumab, a PD-L1 inhibitor, could serve as an effective approach for certain subgroups of patients with GIST, Rurkowski suggests.

Rutkowski states that the AXAGIST trial represents the largest study exploring the combination of immunotherapy and TKI in this patient population to date. Study findings demonstrate that the combination was well tolerated and may provide an effective therapeutic option for patients with GIST who have limited treatment choices. This study may pave the way for future investigations of immunotherapy combinations in this setting, particularly for those with specific molecular subtypes of GIST.