Colorectal cancer

In the early stages of CRC, there are now a range of treatment options available and as a result survival rates have improved significantly over the past 20 years.1 Yet for those with advanced disease who don’t respond to earlier lines of therapy, the options are limited. In fact, for people whose disease has progressed after receiving two rounds of treatment, nearly half in Europe and in the US will receive no further treatment at all.2,3 This may be due to the limited options for third-line treatment,4 coupled with poor overall survival from second to third line treatment.5

Early symptoms of CRC can include abdominal pain and blood in bowel movements, although these can easily be confused with those of other diseases, such as Irritable Bowel Syndrome, Crohn’s disease or peptic ulcers.6

Although advances in screening have reduced mortality, 20% of people with CRC have metastatic disease at initial diagnosis.8,9 This means that their cancer has spread to other parts of the body, making treatment more complicated and their prognosis worse.10

Initial treatment for CRC typically consists of a chemotherapy either administered alone or in combination with a biological therapy.1 However, for those people with advanced CRC – whose cancer has progressed on other treatments – the options are far more limited.11 In fact many people at this stage receive no treatment at all.

Checkpoint inhibitors, a type of immunotherapy that can kick start the immune system into fighting cancer, have recently emerged as a treatment option for a small subset (3-5%) of people with advanced CRC. People with these tumours have a biology described as “microsatellite instability-high” (MSI-H), which increases the likelihood that the body’s own immune system is able to detect the tumour.12

The remaining group, accounting for around 95% of people with advanced CRC, has disease commonly described as “microsatellite stable” (MSS). For these people the immune system is most often not able to engage with the tumour and monotherapy checkpoint inhibitors have currently not been shown to be effective. With this in mind, researchers are now exploring how they could expose CRC to the immune system by designing combination treatments that trigger an immune response.

Stefanie Srock, Group International Medical Director at Roche, said: “It is clear that for people with advanced colorectal cancer their treatment options are limited. In fact, many receive no treatment at all which can lead to their health deteriorating rapidly. New treatments are desperately needed to improve the lives of people living with advanced colorectal cancer.”

Research continues to address this medical need in advanced colorectal cancer.

References

1. Van Cutsem E, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386-422.

2. Tampellini M, et al. Treatment of patients with metastatic colorectal cancer in a real-world scenario: probability of receiving second and further lines of therapy and description of clinical benefit. Clin Colorectal Cancer. 2017;16(4):372-376.

3. Abrams TA, et al. Chemotherapy usage patterns in a US-wide cohort of patients with metastatic colorectal cancer. J Natl Cancer Inst. 2014;106(2):djt371.

4. Carter NJ, et al. Regorafenib: a review of its use in previously treated patients with progressive metastatic colorectal cancer. Drugs Aging. 2014;31(1):67-78.

5. Hanna N, et al. Survival benefit associated with the number of chemotherapy/biologic treatment lines in 5,129 metastatic colon cancer patients. Poster presented at: The American Society of Clinical Oncology 2014 Gastrointestinal Cancers Symposium; 2014 Jan 18; San Francisco, CA, USA. Abstract #559.

6. John SKP, et al. Symptoms and signs in patients with colorectal cancer. Colorectal Dis. 2011 Jan;13:17-25.

7. WHO [Internet; cited 26 April 2019.] Available from:

8. Riihimaki M, et al. Patterns of metastasis in colon and rectal cancer. Sci Rep. 2016;6:29765.

9. Shahidi N, Cheung WY. Colorectal cancer screening: Opportunities to improve uptake, outcomes, and disparities. World J Gastrointest Endosc. 2016;8(20):733-40.

10. Henley SJ et al. Surveillance of screening-detected cancers (colon and rectum, breast, and cervix) – United States, 2004-2006. MMWR Surveill Summ. 2010;59(9):1-25.

11. Yang Q, et al. Bevacizumab plus chemotherapy as third- or later-line therapy in patients with heavily treated metastatic colorectal cancer. Onco Targets Ther. 2015;8:2407-13.

12. Overman MJ et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182-1191.