Joleen Hubbard, M.D.
Deputy Director for Clinical Research
Allina Health Cancer Institute

Over the last several decades, cancer treatment has undergone a revolution driven in part by improvements in our understanding of the complex drivers behind the disease.

 However, the rapid pace of therapeutic development is not equal among all cancer types, sometimes leaving patients behind. Colorectal cancer (CRC) has historically been one such area.

CRC is the world’s third most common cancer, resulting in nearly 935,000 associated deaths in 2020.

 Some estimates predict that the global burden of CRC will increase by 60%, to more than 2.2 million new cases and 1.1 million deaths yearly by 2030.

 Even with its prevalence, CRC remains one of the most challenging cancers to treat, particularly in patients who are either diagnosed with or progress to metastatic CRC (mCRC). Although CRC may be surgically resected in early stages, many patients with CRC will experience metastatic disease, whether at diagnosis or after treatment.

 Metastasis is the leading cause of CRC-related mortality and unfortunately only about 16% of patients in the United States with distant mCRC are still living 5 years after diagnosis.

The poor outcomes some patients with mCRC often face are due in part to the fact that mCRC is a highly heterogenous disease, making the development of targeted treatments difficult. In many other cancers, targeted therapies are more abundant, but, despite significant research efforts, there is still a relative lack of targeted treatments available that address the alterations that patients with mCRC often have.

Given there have been limited options in our armamentarium for patients with mCRC, particularly following relapse, we often run out of tools quickly. This can make treatment planning and sequencing critical to ensure my patients have the chance to receive all available treatment options. The median duration of progression-free survival and the likelihood of achieving a response both decrease with each successive line of therapy, which makes pairing the right therapy to the right patient at the right time imperative.

The Consequences of Limited Treatment Options

Because of challenges in the development of targeted therapies for CRC, chemotherapy has been a mainstay treatment. However, those with more aggressive forms of cancer may experience relapses. Chemotherapy-free options have been scarce, and many patients have faced an uncertain path forward once they experience multiple relapses. 

They have often been left with the option to toggle between retrying chemotherapies they’ve already received interspersed with the few targeted therapy options currently available.

 As a physician, I strive to offer my patients more. The limited arsenal of targeted therapies has posed a significant challenge, leaving physicians grappling with the unfortunate reality that the treatment options that have been available may offer limited survival benefit and may cause challenging side effects for certain patients.

The emotional toll and physical exhaustion patients experience after running out of new treatment options places a substantial burden on them and can result in reduced quality of life and patient experience alongside worse survival outcomes.

Considering a patient’s quality of life against the need to attack their cancer as aggressively as possible is a constant balancing act. For example, patients may have a compromised health status that makes it more difficult to tolerate certain therapies or they may desire a break from spending time in infusion centers or hospitals after receiving chemotherapy treatments, radiation or surgery. This, coupled with complexities that have been introduced to the treatment landscape with diagnoses of metastatic CRC now occurring at increasingly younger ages – such as fertility concerns and raising young children – makes the need for treatment innovation all the more critical.

I am optimistic about the future of mCRC, despite having had limited treatment options available and the challenges that patients face. There is progress on the horizon. Recently, a novel treatment option was approved by the U.S. Food and Drug Administration for patients regardless of their biomarker status, and there are a number of RAS inhibitors being investigated as potential solutions. Anticipation for therapeutic advancement is palpable within the CRC community, and it is encouraging to see that novel options are arriving on the market. Despite this, there is more work to be done, and it is critical that the CRC community comes together to continue to optimize treatment strategies, innovate, and identify more opportunities so that patients can live longer and meet the milestones they so desperately wish to experience.

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Joleen Hubbard, M.D., Deputy Director for Clinical Research at Allina Health Cancer Institute

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