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TAT 2019: Trends in Distribution of Cancer Type in Phase I Trials

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Key Points

  • The proportion of phase I trials in which patients with either colorectal or lung cancer accounted for at least half of the enrolled group declined markedly over time, from 46.3% in 1991–1995 to just 16.7% in 2011–2015.
  • The absolute number of trials involving a majority of patients with either colorectal or lung cancer still rose over the period—from 31 to 41—but this was far less than the increase in trials focused on rarer cancer types.
  • The 1991–2015 time span chosen for the analysis coincides with changes in cancer therapy, driven by the development of molecularly targeted anticancer drugs and application of comprehensive molecular profiling techniques for patient selection in clinical trials.
  • The new study fails to fully reflect a second much more recent revolution in cancer medicine—the arrival of immunotherapy.

The proportion of early-stage drug trials tackling the most common tumor types has declined sharply since the early 1990s, as less common cancers receive increasing attention in trials, according to new research presented by Sato et al at the TAT 2019–International Congress on Targeted Anticancer Therapies (Abstract 30P).

Our study clearly shows the common cancer types are decreasing as a proportion of the patients in phase I studies and the uncommon types are increasing,” said lead author Jun Sato, MD, of the National Cancer Center Hospital, Japan. “The development of new treatment options means there are now multiple approaches to address an increasingly broad spectrum of different types of cancer.”

Methods and Findings

Dr. Sato and his colleagues pooled results from 866 oncology phase I trials conducted worldwide for their analysis. These trials, published between 1991 and 2015, involved more than 29,000 patients enrolled to test novel medicines in the first stage of clinical testing.

They found that the proportion of phase I trials in which patients with either colorectal or lung cancer accounted for at least half of the enrolled group declined markedly over time, from 46.3% in 1991–1995 to just 16.7% in 2011–2015. The trend was consistent across North America, Europe, and Asia. The absolute number of trials involving a majority of patients with either colorectal or lung cancer still rose over the period—from 31 to 41—but this was far less than the increase in trials focused on rarer cancer types.

Lung and colorectal cancer are the most common causes of cancer death globally, accounting for 2.6 million of an estimated 9.6 million cancer deaths in 2018, according to the World Health Organization.

The 1991–2015 time span chosen for the analysis coincides with changes in cancer therapy, driven by the development of molecularly targeted anticancer drugs and application of comprehensive molecular profiling techniques for patient selection in clinical trials. Initially, from the 1990s to the early 2000s, scientists used these advances to investigate large cancer populations with frequent genomic mutations, but over time, the focus of genomic-driven clinical trials has shifted to less common mutations and rarer tumor types.

“There has been a natural evolution to infrequent tumor types, such as biliary tract cancers, due to a better understanding of the genomic drivers and altered pathways in these malignancies. Besides, common cancers like lung adenocarcinomas are now classified into multiple rarer subtypes based on genomic markers,” said Rodrigo Dienstmann, MD, of the Oncology Data Science Unit at the Vall d'Hebron Institute of Oncology, Barcelona.

Still, the new study does not tell the full story, since it fails to fully reflect a second much more recent revolution in cancer medicine—the arrival of immunotherapy. Because the data analyzed comes from trials published up to 2015, when immuno-oncology was in its infancy, it does not include the rapid growth in immunotherapy clinical trials over the past few years. “This study won’t have really captured the explosion in immunotherapy trials that we have seen,” Dr. Dienstmann said.

Lung cancer is one notable field where new immunotherapy treatments like immune checkpoint inhibitors have proven particularly promising. As a result, Dr. Dienstmann believes there has been a bounce back in the proportion of phase I trials addressing lung tumors since 2015.

Overall, the clinical trial landscape is increasingly focused on immunotherapy, with more than 2,200 trials now evaluating immune checkpoint inhibitors, according to the Cancer Research Institute.

Interestingly, both targeted therapies and immunotherapies have proven largely ineffective in colorectal cancer, except immune checkpoint inhibitors in microsatellite-unstable tumors.

“We get a lot of [patients with] colorectal [cancer] who have run through standard treatments, and it is very difficult to put them into phase I trials because there are not many new options,” said Markus Joerger, MD, PhD, of the phase I unit at the St. Gallen Cancer Centre, Switzerland.

Despite such challenges, the latest analysis shows there is a vibrant field of clinical research into new approaches for tackling cancer, with the picture proving particularly positive for patients with rare tumor types that have typically received limited attention in the past.

“Across all cancer types, what we are seeing is more and more phase I trials, reflecting the latest waves of innovation,” Dr. Joerger concluded.

Disclosure: The study authors' full disclosures can be found at cslide.ctimeetingtech.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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