Second-line outcomes in metastatic colorectal cancer – raising the bar for the high jump rather than the doing the limbo

Abstract

Metastatic colorectal cancer is a significant burden to patients and healthcare systems worldwide. While outcomes have improved in the past 20 years, gains in survival in the second-line setting have been achieved at a significant monetary cost. The American Society of Clinical Oncology recently published guidelines on the definition of a clinically meaningful outcome as the measure of success of a therapy. We reviewed the FDA labels for drugs used in the second-line treatment of metastatic colorectal cancer and found that outcomes fell short of American Society of Clinical Oncology’s definition of clinically meaningful. There was also variation in the methods used to determine cost–effectiveness and value of outcomes. We discuss these observations and the challenges associated with justifying payment for expensive drugs that often only achieve marginal benefits.

Keywords:

• colorectal cancer
• cost–effectiveness
• meaningful outcomes
• second-line
• value

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Many outcomes measured in trials of second-line therapy for metastatic colorectal cancer have hitherto failed to meet the new definitions proposed by the American Society of Clinical Oncology as being clinically meaningful.

• The American Society of Clinical Oncology recommends that overall survival be the primary outcome measured in second-line and later lines of therapy for metastatic colorectal cancer.

• There is significant variability in methods reported in the literature to measure cost–effectiveness of outcomes in second-line treatment of colorectal cancer, thus limiting the applicability of these results when determinations of cost–effectiveness are needed to recommend approval of coverage of these drugs by health technology assessment agencies.

• Streamlining assessments of cost–utility by creating predefined parameters and flow diagrams for cost assessments incorporated in clinical trials may enable cross-comparisons between trials and interventions.

• Engagement of key stakeholders, patients, advocates, physicians, pharmaceutical companies, payers and approval bodies, is vital to define the value of outcomes.

Notes

HR: Hazard ratio.