Traditional therapies still offer added value and benefits in all cancer treatments

Robert L. Ferris, MD, PhD

director

Hillman Cancer Center

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania

This is currently being debated in oncology. The best cancer therapies treat the right patient groups with “non-specific” but effective therapies such as chemotherapy or radiotherapy. We have decades of experience with broad-spectrum chemotherapies such as platinum compounds, taxanes and even the recently developed apoptosis inhibitors. Should our goal be to identify the mechanisms and patients most likely to benefit from these non-specific therapies?

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

On the one hand, there are cheaper, broad-spectrum drugs that have been used for decades to treat toxicities and whose financial benefits are not patented for the health system and patients. The challenge is to find out why some patients benefit and others do not. Then, in large clinical trials, biomarkers for these broad-spectrum drugs must be identified and combinations developed to increase their effectiveness and identify the patient groups that will benefit.

On the other hand, a whole field of precision oncology has emerged that is promising but offers few examples of success. In fact, large National Cancer Institute (NCI)-funded studies such as the NCIMATCH (Molecular Analysis for Therapy Choice) trial have shown that only about 20% of patients have alterations that can be treated with an available agent. Non-small cell lung cancer is certainly a wonderful example, and the story of RAS is also instructive, as a previously untreatable target now has multiple active agents.

Examples exist in all areas of oncology and across all cancers where we need to prioritize developing biomarkers for patients and think about the type of treatment that will be most effective. As in the medical-industrial complex and government-funded academic research in collaboration with industrial science, rational and compelling approaches to developing the best therapies targeting the tumor and microenvironment are ongoing under the general concepts described here and have accelerated in recent years. Still, we should not forget the agents that are cheap and proven, and we should continue to work to figure out how they work and who they work for, alongside exciting efforts in precision oncology.