Are we finally moving toward personalized therapy in colorectal cancer?

Editorial


Are we finally moving toward personalized therapy in colorectal cancer?


S. Gill, MD, MPH, MBA*


doi: http://dx.doi.org/10.3747/co.26.5943

Colorectal cancer (crc) will represent 12% of all new cancer cases and 12% of all cancer deaths in 2019, with more than 26,300 Canadians being diagnosed and 9500 Canadians dying of crc this year1. This disease is the 2nd leading cause of death from cancer in men and the 3rd leading cause of death from cancer in women. Despite the significant burden of crc, therapeutic advances since 2009 can be recognized as having translated into better survival outcomes for patients. Still, much remains to be done. In this special supplement to Current Oncology, we review the changing multimodality landscape of crc management, with its increasing focus on the importance of multidisciplinary care and a tailored strategy.

In this issue, Drs. Fournier and Brown ask the surgical question “Can less be more?”2. A paradigm shift is occurring in the surgical management of rectal cancer: from a standard of resection with total mesorectal excision for all, to options of local excision and organ-preserving strategies for carefully selected patients with favourable histopathology. The organ-sparing approach acknowledge the significant morbidity and quality of life implications of rectal cancer surgery, and the importance of multidisciplinary care and review.

For patients with early-stage resected crc, the question of who is most likely to benefit from adjuvant chemotherapy remains an important clinical challenge. Dr. Bender and colleagues3 review the current evidence supporting adjuvant chemotherapy and its optimal duration, and the approach to risk-stratification in the adjuvant setting. From clinicopathologic criteria to the exciting opportunity that lies in the assessment of minimal residual disease by circulating tumour dna, those authors emphasize how personalizing decision-making about adjuvant therapy helps the patients most likely to benefit from adjuvant chemotherapy while sparing patients with low-risk disease from unnecessary toxicity.

Despite best efforts, an estimated 35% of patients with early-stage disease will relapse and another 20%–25% will present with synchronous metastatic disease. The systemic therapy options for patients with unresectable metastatic crc have improved, with consequent improvements in median survival now approaching 30 months in contemporary clinical trials4. However, with the recent recognition of the molecular heterogeneity of crc, one-size therapy no longer fits all. Drs. Jin and Hubbard5 review the considerations that currently define optimal sequencing of biologic therapy in the first-line setting, highlighting the importance of primary tumour location and RAS mutation status in identifying patients most likely to benefit from upfront therapy targeting the epidermal growth factor receptor. Drs. Lee and Loree6 extend that discussion in their comprehensive review of the state of the art in molecular stratification of crc, particularly as it relates to the prognostic and predictive utility of critical biomarkers such as mismatch repair and RAS and BRAF in the management of advanced crc.

In the post-progression setting, the number of patients who have exhausted standard chemotherapy options and yet are still well enough to pursue further therapies is increasing. In their review, Dr. Parmar and colleagues7 provide an evidence-based perspective of that clinically challenging setting. In recent years, new therapeutic options have emerged for chemorefractory disease, including the oral multikinase inhibitor regorafenib and the oral cytotoxic agent trifluridine/tipiracil. Although associated with modest survival benefits, those agents do have a recognized clinically meaningful benefit in an area of considerable unmet need8. However, significant challenges remain and better, more precise therapies are needed.

Finally, although treatment advances in crc have been largely and appropriately driven by randomized controlled trials, appreciation is growing for the utility of real-world evidence to improve the generalizability of new therapies to the entire population and to inform the optimal use of therapies in diverse patient populations. In their insightful review, Drs. Batra and Cheung provide an overview of the strengths and limitations of real-world evidence and the knowledge gaps that such evidence has addressed, translating the best of that evidence into clinical practice in crc.

As evidenced in this supplement, considerable progress has been made in the management of crc, which is good news for our patients. A more personalized approach is emerging in crc, including, but not limited to, consideration for tumour molecular heterogeneity, clinicopathologic features, and patient preferences. I thank and congratulate all the authors for their excellent contributions, and I hope that this special issue of Current Oncology will prove to be a valuable educational resource for our oncology community of care providers and patients.

CONFLICT OF INTEREST DISCLOSURES

I have read and understood Current Oncology’s policy on disclosing conflicts of interest, and I declare the following related interests: I have received speaker fees or advisory board honoraria from Amgen, Taiho, Roche, and Bayer.

AUTHOR AFFILIATIONS

*BC Cancer, Vancouver, BC.

REFERENCES

1 Canadian Cancer Statistics Advisory Committee. Canadian Cancer Statistics 2019. Toronto, ON: Canadian Cancer Society; 2019. Available online at: http://www.cancer.ca/~/media/cancer.ca/CW/publications/Canadian%20Cancer%20Statistics/Canadian-Cancer-Statistics-2019-EN.pdf; cited 4 October 2019]

2 Fournier FR, Brown CJ. Can less be more? Organ preservation strategies in the management of rectal cancer. Curr Oncol 2019;26(suppl 1):S16–23.

3 Bender U, Rho YS, Barrera I, Aghajanyan S, Acoba J, Kavan P. Adjuvant therapy for stages ii and iii colon cancer: risk stratification, treatment duration, and future directions. Curr Oncol 2019;26(suppl 1):S43–52.

4 Venook AP, Niedzwiecki D, Lenz HJ, et al. Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: a randomized clinical trial. JAMA 2017;317:2392–401.
cross-ref  pubmed  pmc  

5 Jin Z, Hubbard JM. Optimizing biologic sequencing in metastatic colorectal cancer: first line and beyond. Curr Oncol 2019;26(suppl 1):S33–42.

6 Lee MKC, Loree JM. Current and emerging biomarkers in metastatic colorectal cancer. Curr Oncol 2019;26(suppl 1):S7–15.

7 Parmar A, Chan KKW, Ko YJ. Metastatic colorectal cancer: therapeutic options for treating refractory disease. Curr Oncol 2019;26(suppl 1):S24–32.

8 Ko YJ, Abdelsalam M, Kavan P, et al. What is a clinically meaningful survival benefit in refractory metastatic colorectal cancer? Curr Oncol 2019;26:e255–9.
cross-ref  pubmed  pmc  

9 Batra A, Cheung WY. Role of real-world evidence in informing cancer care: lessons from colorectal cancer. Curr Oncol 2019;26(suppl 1):S53–6.


Correspondence to: Sharlene Gill, BC Cancer–Vancouver, 600 West 10th Avenue, Vancouver, British Columbia V5Z 4E6. E-mail: sgill@bccancer.bc.ca

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Current Oncology, VOLUME 26, SUPPLEMENT 1, November 2019








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ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)