Number of patients eligible for genome-driven oncology therapy is increasing, but the percentage who reportedly benefit from the therapy remains at less than 5%

Advances in precision medicine in oncology (precision oncology) are fueling the need for clinical laboratory companion diagnostic tests that help physicians choose the best treatment protocols. In fact, this is a fast-growing area of clinical diagnostics for the nation’s anatomic pathologists. However, some experts in the field of genome-based cancer treatments disagree over whether such treatments offer more hype than hope.

At an annual meeting of the American Association for Cancer Research (AACR) in Chicago, David Hyman, MD, Chief of Early Drug Development at Memorial Sloan Kettering Cancer Center in New York, and Vinay Prasad, MD, MPH, Hematologist-Oncologist and Associate Professor of Medicine at Oregon Health and Science University (OHSU), squared off.

Science, a journal of the American Association for the Advancement of Science (AAAS), reported that during a panel discussion, titled, “Is Genome-Informed Cancer Medicine Generating Patient Benefit or Just Hype?,” Prasad argued precision oncology benefits far fewer advanced cancer patients than headlines suggest. “When you look at all the data, it’s a sobering picture,” he told the AACR attendees.

To support his claim, Prasad pointed to a study he co-authored that was published in JAMA Oncology, titled, “Estimation of the Percentage of US Patients with Cancer Who Benefit from Genome-Driven Oncology.”

Prasad and his colleagues evaluated 31 US Food and Drug Administration (FDA) approved drugs, which were “genome-targeted” or “genome-informed” for 38 indications between 2006 and 2018. The researchers sought to answer the question, “How many US patients with cancer are eligible for and benefit annually from genome-targeted therapies approved by the US Food and Drug Administration?”

They found that in 2018 only 8.33% of 609,640 patients with metastatic cancer were eligible for genome-targeted therapy—though this was an increase from 5.09% in 2006.

Even more telling from Prasad’s view, his research team concluded that only 4.9% had benefited from such treatments. Prasad’s study found the percentage of patients estimated to have benefited from genome-informed therapy rose from 1.3% in 2006 to 6.62% in 2018.

“Although the number of patients eligible for genome-driven treatment has increased over time, these drugs have helped a minority of patients with advanced cancer,” the researchers concluded. “To accelerate progress in precision oncology, novel trial designs of genomic therapies should be developed, and broad portfolios of drug development, including immunotherapeutic and cytotoxic approaches, should be pursued.”

The graph above is based on data from a study published in Science titled, “Estimation of the Percentage of US Patients With Cancer Who Benefit from Genome-Driven Oncology,” co-authored by Vinay Prasad, MD, MPH, et al. (Image copyright: Science.)

A Value versus Volume Argument?

Hyman, who leads a team of oncologists that conduct dozens of clinical trials and molecularly selected “basket studies” each year, countered Prasad’s assertions by noting the increase in the number of patients who qualify for precision oncology treatments.

As reported in Science, Hyman said during his AACR presentation that Sloan Kettering matched 15% of the 25,000 patients’ tumors it tested with FDA-approved drugs and 10% with drugs in clinical trials.

“I think this is certainly not hype,” he said during the conference.

Hyman added that another 10% to 15% of patient tumors have a DNA change that matches a potential drug tested in animals. He expects “basket” trials to further increase the patient pool by identifying drugs that can work for multiple tumor types.

The US National Institute of Health (NIH) describes “basket studies” as “a new sort of clinical studies to identify patients with the same kind of mutations and treat them with the same drug, irrespective of their specific cancer type. In basket studies, depending on the mutation types, patients are classified into ‘baskets.’ Targeted therapies that block that mutation are then identified and assigned to baskets where patients are treated accordingly.”

Are Expectations of Precision Medicine Exaggerated?

A profile in MIT Technology Review, titled, “The Skeptic: What Precision Medicine Revolution?,” describes Prasad’s reputation as a “professional scold” noting the 36-year-old professor’s “sharp critiques of contemporary biomedical research, including personalized medicine.” Nevertheless, Prasad is not alone in arguing that precision oncology’s promise is often exaggerated.

Following the Obama Administration’s 2015 announcement of its precision medicine initiative, Michael J. Joyner, MD, Professor of Anesthesiology at the Mayo Clinic, penned a New York Times (NYT) editorial in which he cast doubt on the predictive power of genetic variants to improve disease outcomes.

“Like most ‘moonshot’ medical research initiatives, precision medicine is likely to fall short of expectations,” Joyner wrote. “Medical problems and their underlying biology are not linear engineering exercises and solving them is more than a matter of vision, money, and will.”

Recently, he increased his dissent over current perceptions of precision medicine’s value. In a STAT article, titled, “Precision Medicine’s Rosy Predictions Haven’t Come True. We Need Fewer Promises and More Debate,” Joyner and co-author Nigel Paneth, MD, MPH, Professor of Epidemiology and Biostatistics and Pediatrics at Michigan State University, pushed for more debate over the “gene-centric paradigms” that now “pervade biomedical research.”

“Although some niche applications have been found for precision medicine—and gene therapy is now becoming a reality for a few rare diseases—the effects on public health are miniscule while the costs are astronomical,” they wrote.

Hope for Precision Medicine Remains High

However, optimism over precision oncology among some industry leaders has not waned. Cindy Perettie, CEO of molecular information company Foundation Medicine of Cambridge, Mass., argues genome-directed treatments have reached an “inflection point.”

“Personalized cancer treatment is a possibility for more patients than ever thanks to the advent of targeted therapies,” she told Genetic Engineering and Biotechnology News. “With a growing number of new treatments—including two pan-tumor approvals—the need for broad molecular diagnostic tools to match patients with these therapies has never been greater. We continue to advance our understanding of cancer as a disease of the genome—one in which treatment decisions can be informed by insight into the genomic changes that contribute to each patient’s unique cancer.”

Prasad acknowledges genome-driven therapies are beneficial for some cancers. However, he told MIT Technology Review the data doesn’t support the “rhetoric that we’re reaching exponential growth, or that is taking off, or there’s an inflection point” signaling rapid new advancements.

“Right now, we are investing heavily in immunotherapy and heavily in genomic therapy, but in other categories of drugs, such as cytotoxic drugs, we have stopped investigating in them,” he told Medscape Medical News. “But it’s foolish to do this—we need to have the vision to look beyond the fads we live by in cancer medicine and do things in a broader way,” he added.

“So, I support broader funding because you have to sustain efforts even when things are not in vogue if you want to make progress,” Prasad concluded.

Is precision oncology a fad? Dark Daily has covered the advancements in precision medicine extensively over the past decade, and with the launch of our new Precision Medicine Institute website, we plan to continue reporting on further advancements in personalized medicine.

Time will tell if precision oncology can fulfill its promise. If it does, anatomic pathologists will play an important role in pinpointing patients most likely to benefit from genome-driven treatments.

One thing that the debate between proponents of precision medicine in oncology and their critics makes clear is that more and better clinical studies are needed to document the true effectiveness of target therapies for oncology patients. Such evidence will only reinforce the essential role that anatomic pathologists play in diagnosis, guiding therapeutic decisions, and monitoring the progress of cancer patients.

—Andrea Downing Peck

Related Information:

A Cancer Drug Tailored to your Tumor? Experts Trade Barbs over Precision Oncology

Estimation of the Percentage of US Patients with Cancer who Benefit from Genome-Driven Oncology

2020 Vision: Predictions of What May Shape Precision Medicine

Precision Medicine’s Rosy Predictions Haven’t Come True. We Need Fewer Promises and More Debate

The Skeptic: What Precision Medicine Revolution?

‘Moonshot’ Medicine Will Let Us Down

Basket Studies: An Innovative Approach for Oncology Trials

‘Genome-Driven’ Cancer Drugs Treat Small Minority of Patients

Press Release: The All-New Precision Medicine Institute Website Makes Its Debut

Harvard Medical School Study Finds ‘Staggering’ Amounts of Genetic Diversity in Human Microbiome; Might Be Useful in Diagnostics and Precision Medicine

McKinsey and Company Report Highlights Precision Medicine’s Advancements in Integrating Genetic Testing Results with Electronic Medical Records

Precision Medicine’s Most Successful Innovators to Speak in Nashville, including Vanderbilt Univ. Med. Center, Illumina, Geisinger Health, Northwell Health

Targeted Cancer Therapies Bring New Precision Medicine Tools to Anatomic Pathologists and Clinical Laboratories