What is a clinically meaningful survival benefit in refractory metastatic colorectal cancer?

Assessment of the clinical benefit of cancer treatments can be highly subjective, influenced by both perspective and context. Such assessments are required in regulatory and policy decision-making, but consistency between jurisdictions is often lacking. Clear and consistent standards for determining when a treatment offers a meaningful benefit, relative to the current standard of care, can help to address issues of equity and transparency in health technology assessment. For metastatic colorectal cancer (mcrc), no standardized Canadian definition of clinically meaningful benefit has yet been proposed. Colorectal Cancer Canada therefore convened a group of medical oncologists expert in colorectal cancer to review the literature about clinical significance. The resulting consensus is intended to apply to any therapeutic agent being considered in the setting of chemotherapy-refractory mcrc. It was agreed that overall survival is the appropriate measure of clinical efficacy in chemorefractory mcrc. As quantitative targets for efficacy, an improvement of 2 months or more in median overall survival or a hazard ratio for survival of 0.75 or lower (or both) are proposed as the threshold for clinically meaningful benefit. That threshold could be influenced by a treatment's effect on quality of life. Treatment toxicity is also relevant to the assessment of clinical benefit in this setting, specifically when significant differences in treatment tolerability are evident.
Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare the following interests: YJK has received honoraria for advisory or speaking roles from Taiho, Amgen, Servier, and Eli Lilly; MA has received honoraria for advisory or speaking roles from AstraZeneca, Boehringer Ingelheim, Bristol–Myers Squibb, Celgene, Ipsen, Janssen, Johnson and Johnson, Merck, NB Urology, Novartis, Pfizer, Roche, Sanofi, Shire, Taiho, and Yewtree Consulting; he is a co-investigator or principal investigator on industry trials sponsored by AbbVie, Amgen, Aragon Pharmaceuticals, Astex Pharmaceuticals, Astra-Zeneca, Bayer, Boehringer Ingelheim, Bristol–Myers Squibb, the Canadian Cancer Trials Group, Chiltern/Pfizer, Eisai, Exactis Innovation, GlaxoSmithKline, Merck and Co., Merck KGaA, Novartis, Odonate Therapeutics, Pharmacyclics, Picomole, Puma Biotechnology, Purdue Pharma, the Quebec Clinical Research Organization in Cancer, Roche, Sanofi Aventis, Takeda, Turnstone Biologics, and United Therapeutics; PK has received honoraria for advisory roles from Amgen, Taiho, and Merck; he has also received educational grants from Amgen, Bayer, Merck, Roche, and Taiho; HL has received honoraria for advisory roles from Roche, Amgen, Eisai, Taiho, Lilly, and Bristol–Myers Squibb; he has also received travel support from Eisai and is a co-investigator or principal investigator on industry trials sponsored by Bristol–Myers Squibb, AstraZeneca, Amgen, Roche, and Astellas; PAT has received honoraria for advisory or speaking roles from Novartis, Genomic Health International, Amgen, Merck, Taiho, and AstraZeneca; MV has received honoraria for advisory or speaking roles from Taiho, Merck, Bristol–Myers Squibb, Boehringer Ingelheim, Eli Lilly, Sanofi Aventis, Amgen, Novartis, Pfizer, Roche, Amgen, and AstraZeneca; SG has received honoraria for advisory or speaking roles from Amgen, Roche, Taiho, and Eli Lilly. The remaining authors have no conflicts of interest to disclose.