We recently announced preliminary data from a randomized Phase II clinical trial of REOLYSIN® in combination with FOLFOX-6 and bevacizumab (Avastin®) in patients with advanced or metastatic colorectal cancer (IND 210). What was unique about this data? There was a significant difference in how female patients in the test arm versus the control arm responded to the treatment. In this blog post, we’ll talk about why different response rates might occur in different groups and what this means for therapies like REOLYSIN®.
IND210 Results Recap
When we reviewed the data from IND210 according to our study protocol, we found the male patients in the test arm had an objective response rate of 46.9% (n=32) versus 41.9% (n=31) in the control arm (p=0.6747), while the female patients in the test arm had an objective response rate of 63.2% (n=19) versus 23.8% (n=21) in the control arm (p=0.0054). This contrast caused us to do a double take…
Of course, we were encouraged by this data—it suggests that the inclusion of REOLYSIN® in the treatment combination may have a profound impact on response rates for women with colorectal cancer.
This is another example of our sponsored randomized Phase II program identifying specific indications, patient populations and endpoints for examination in future trials. Previous examples included the difference noted between the response rates of head and neck cancer patients with primary versus metastatic disease (REO 018).
Why do females respond differently?
Females may respond differently to treatment due to a combination of biomarkers and biological differences, like hormones, between men and women.
A Wall Street Journal article compared how men and women uniquely experience disease and respond to treatment. Looking at lung cancer, they reported that:
“Researchers have found that hormones, particularly estrogen, influence lung-cancer development and mortality. In addition to making women metabolize nicotine more quickly than men, estrogen triggers the estrogen receptors that are present on 45% to 70% of lung cancers, and may also play a role in activating certain genes within tumors that could affect whether cancer responds to treatment.”
In general, cancer therapy is moving away from treating a type of cancer to treating different marker profiles regardless of the cancer type. If we can see that certain genes are present in a tumour, we have an opportunity to leverage knowledge of biomarkers to personalize treatment to a patient’s needs. For example, in colorectal cancer, mutant KRAS can be predictive of whether or not a particular treatment will work.
It could be that women have certain biomarkers or genes within tumours that are activated by different aspects of their biology and affect response to treatments, including REOLYSIN®. In fact, this difference between the sexes and cancer treatment response has been noted before in the use of tyrosine-kinase inhibitors, which also seem to help women more than men.
What’s next for REOLYSIN® and females with colorectal cancer?
Building on our IND210 findings, we are conducting a study in female metastatic colorectal cancer patients using this treatment regimen combined with a checkpoint inhibitor to see how the combination may make cancer cells more susceptible to attack by the immune system. In fact, we recently announced our Investigational New Drug Application containing the protocol titled “Phase 2 study of REOLYSIN® (pelareorep) in combination with FOLFOX6, bevacizumab and pembrolizumab in female patients with KRAS-mutant colorectal cancer metastatic to the liver.” This study is now active.
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