Promising Approaches That Use Targeted Therapy Combinations Are Explored at GI, GU Symposia

Robert L. Ferris, MD, PhD

It is well accepted that for most cancers across settings, the use of combination therapies is the standard of care to maximize outcomes. Indeed, clinical trials evaluating conventional modalities such as chemotherapy with or without radiation in the definitive or postoperative adjuvant setting have focused on most efficacious combinations. Using combination treatments in the concurrent setting with chemotherapy, radiation therapy, or small molecule oncogene and pathway inhibitors may yield positive data in one setting but not another.

Innovative developmental trial designs are necessary and results often get presented at disease-specific meetings like the recent 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers (GI) Symposium or the ASCO Genitourinary (GU) Cancers Symposium. The proliferation of trial acronyms that companies use to develop their trial portfolios (TOPAZ, HIMALAYA, CIRCULATE, etc.) reflects the many phase 2 and phase 3 clinical trials. These symposia focused on combinations of PD-1 inhibitors with radiation, chemotherapy, or targeted inhibitors in the preoperative neoadjuvant setting or postoperative setting for high-risk disease. Furthermore, findings were widely presented in locally advanced or recurrent, chemotherapy-refractory disease.

Overall, trials discussed at these 2 symposia, and detailed in this issue, have reported novel findings using various combinations of IO and small molecule inhibitors, showing that the promise of targeted immunotherapy and genomeguided oncology drugs is rich with new findings and trial designs.

Quite reassuringly, positive data are being seen in early-phase combinations, which bodes well for clinical outcomes in GU and GI cancers. Indeed, improvements in survival with add-on strategies—which are additive or synergistic—are needed to harness the power of greater biological understanding of disease, addressed through cancer immunotherapy and precision oncology.

I recommend reviewing the results of phase 2 and phase 3 randomized trials from the recent disease-specific GI and GU symposia, which are well reported in this issue. These trials contain a wealth of exciting findings and provide a paradigm across other cancers for integrating these novel biologically driven therapies with the conventional regimens and modalities we have used for years.

As we appear to be emerging from the pandemic, it is reassuring that scientific advancements and clinical investigation have kept up and are continuing the progress forward for our patients.