Traditional Therapies Still Bring Value, Benefit Across Cancer Settings

Robert L. Ferris, MD, PhD

Director

Hillman Cancer Center

University of Pittsburgh Medical Center

Pittsburgh, PA

There is a running debate in the field of oncology. The best cancer therapies treat the right populations with “nonspecific” but effective therapies, such as chemotherapy or radiation therapy. We have decades of experience with broadly active chemotherapies, such as the platinum compounds, taxanes, and even the recently developed inhibitors of apoptosis. Should our goal be to identify the mechanisms and patients most likely to benefit from these nonspecific therapies?

Can the genetically driven tumor sequencing field using next-generation sequencing (NGS) panels and, more recently, broad whole-exome sequencing, be paired with recently identified inhibitors, such as targeting altered BRAF, RAS, and other mutated cancer-signaling pathways?

On one hand, cheaper, broadly active compounds with decades of experience in managing toxicities and off-patent financial benefits exist for the health system and patients. The challenge is to identify why some patients benefit and others don’t. Then, large clinical trials need to identify biomarkers for these broadly active agents and to develop combinations to enhance their activity and identify populations who benefit.

On the other hand, an entire field of precision oncology has emerged with exciting promise, but demonstrate selective examples of success. Indeed, large National Cancer Institute (NCI)–funded trials, such as the NCIMATCH (Molecular Analysis for Therapy Choice) Trial, have shown that only approximately 20% of patients have targetable alterations with an available agent. Certainly, non–small cell lung cancer is a wonderful example, and the RAS story is also instructive, as a previously undruggable target now has several active agents.

Examples exist across all of oncology and cancer types where we have to prioritize the approach to developing patient biomarkers and think about the type of treatments that will be most effective. As with the medical industrial complex and federally funded academic research in partnership with industry science, rational and cogent approaches to developing the best therapies targeting the tumor and the microenvironment will continue under the general concepts described here, and have accelerated in recent years. Nonetheless, we should not forget the active agents that are cheap and tried-and-true, and efforts should continue identifying how they work and for whom, alongside the exciting precision oncology efforts.