Dr Bekaii-Saab on the Future of Treatment For Patients With GI Cancer

Tanios Bekaii-Saab, MD, FACP, professor, medicine, Mayo Clinic College of Medicine and Science; leader, Gastrointestinal Cancer Program, Mayo Clinic Comprehensive Cancer Center; medical director, Cancer Clinical Research Office; vice chair, section chief, Medical Oncology, Department of Internal Medicine, Mayo Clinic, discusses the future of treatment within the gastrointestinal (GI) cancers armamentarium.

Within the realm of GI cancer research, one of the key focuses is to advance immunotherapy for microsatellite-stable (MSS) colorectal cancer (CRC) and identify the patients who might benefit from this treatment approach, Bekaii-Saab begins. Although current data are promising, they are not yet convincing, as there is a lack of large studies to firmly establish the role of immunotherapy in CRC and the best methods for selecting patients, he states. Some studies indicate the efficacy of anatomical targeting, such as focusing on lung metastases, according to Bekaii-Saab. Patients with CRC and lung metastases comprise a small population with generally excellent outcomes, Bekaii-Saab reports, adding that some patients with lung-only metastases have gone years without needing treatment, indicating the unique biology of this cancer. Understanding the true effects of immunotherapy in this context requires randomized trials, as the field cannot yet determine the best treatment approach for the majority of patients with CRC with microsatellite stability, he elucidates.

Among ongoing explorations of immunotherapy combinations, the phase 1/2 ARC-9 study (NCT04660812) stands out, he continues. This randomized study evaluated various agents, including etrumadenant (AB928), an oral agent that blocks adenosine receptors. Adenosine signaling impairs the activation, proliferation, and cytotoxic activity of T cells. By blocking adenosine, T cells become more active. Combining adenosine receptor inhibitors with a PD-1 inhibitor, such as zimberelimab (Sepalizumab), enhances immune response, Bekaii-Saab explains, noting that blocking adenosine receptors reactivates the effectiveness of oxaliplatin.

The ARC-9 study was complex, incorporating mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin), bevacizumab (Avastin), etrumadenant, and zimberelimab, with a crossover design, he expands. The results were impressive, showing significant activity when these treatments were combined, compared with standard therapies, Bekaii-Saab emphasizes. This study demonstrates the potential of multi-agent approaches and dose-optimization strategies in improving outcomes for patients with MSS CRC, Bekaii-Saab concludes.