Translational research has the potential to help all patients, but the principles behind bench-to-bedside research hold special promise for patients with rare diseases — many of which have no standard treatments. Here’s how changes to the way rare oncology studies are performed are getting treatments to the patients who need them at a faster rate.
What Makes a Cancer “Rare”?
Rare cancers are defined by having an incidence rate of less than 6 per 100,000. With dozens of different conditions, however, altogether rare cancers have an incidence as high as 108/100,000. That comes out to 541,000 new cases diagnosed every year in Europe alone, with 4.3 million people living with these conditions.
As a group, “rare” cancers are actually the seventh most common type, representing roughly 22 percent of all cancers. Of those, hematological cancers are the most common subgroup. Unfortunately, the five-year overall survival rate for patients with rare cancers is just 47 percent, compared to 65 percent in the general oncology population. This disparity is partly caused by the relative lack of research available thanks to a number of complicating factors.
Challenges in Rare Oncology Research
By definition, rare cancers affect a relatively low number of people, making the potential recruitable population for these studies a very small one that is scattered geographically. Many of these conditions also have no baseline standards of care or defined biomarkers. Diagnosis of these diseases is also uncertain, with some 10 to 15 percent of diagnoses having the possibility of being incorrect.
Additional ethical issues often arise in rare oncology trials. Placebo controls or exposure to ineffective doses in these cases is often not ideal. Also, rare cancers often affect children, bringing up general concerns for conducting experiments in juvenile populations.
The best way to serve a geographically dispersed population? Bring them together. Collaborative study groups work with patients and researchers around the globe to address many of the logistical issues inherent in rare oncology. Some of the most well-known groups include the International Rare Cancers Initiative, the Alliance for Clinical Trials in Oncology, and the Pediatric Brain Tumor Consortium.
Innovations in Study Design
Both standard and adaptive design strategies are also changing the face of rare oncology research. This includes a number of alterations — all of which are prospective and approved by relevant regulatory bodies — that expedite the clinical trial process while also retaining scientific integrity. Some study design solutions include randomized phase 2 trials with earlier endpoints and adjusted acceptable alpha and beta errors.
While there are no special methods for designing, carrying out or analyzing clinical trials in small populations, there are strategies for improving efficiency. In these cases, surrogate endpoints need to be justified, with their relationship to clinical efficacy clear enough to allow for proper risk/benefit analyses.
More researchers are also making use of patient registries, which provide:
- A deeper understanding of the natural history of disease
- A source for historical controls
- Supplemental high-quality data
For a deeper look at the innovations happening in rare oncology today, take a look at our recent webinar From Laboratory to Bedside: Expediting Development of Novel Rare Cancer Treatments.