Background Key data in the decision process regarding chemotherapy include the response rate, median duration of response, and median survival, along with functional status, toxicity, and quality of life information (see Fast Fact #14). This Fast Fact reviews the terms and concepts of common clinical endpoints that are used to assess various systemic cancer treatments in the published literature. Additionally, this Fast Fact will synthesize available 5-year survival data for common cancer types to assist generalist clinicians and palliative care specialists who may be asked to help patients and families work through difficult decisions regarding whether to pursue systemic cancer treatment.
Definitions of Relevant Clinical Endpoints for Systemic Cancer Therapies
- Overall Response Rate: the proportion of patients with complete and partial response (complete and partial response are usually predefined terms based on radiologic or hematologic endpoints) to a cancer treatment compared to non-responders.
- Duration of Response: the time from documentation of tumor response to disease progression. In many cancer studies, median duration of response is used, which means the duration in which 50% of patients responded for a shorter period and 50% of patients responded longer. Of note, this data usually excludes non-responders to the cancer treatment.
- Overall survival: time from exposure or randomization to a cancer treatment until death from any cause. Median survival means the length of time in which 50% of patients lived shorter and 50% lived longer. Note: survival data includes both responders and non-responders.
- Progression free survival (PFS): time from exposure of the cancer treatment until either disease progression or death. Usually utilized for patients with advanced or late-stage cancers. Somewhat similar terms include time to progression (excludes deaths) and disease-free survival (usually refers to localized or earlier-staged cancers in which treatment renders the patient disease-free). Controversially, PFS is used increasingly as a primary outcome in cancer research, despite having relatively poor correlation to the more patient-centered outcome of overall survival.
- Time to treatment failure: time from exposure to discontinuation of the cancer treatment for any reason including disease progression, death, but also treatment toxicity. This endpoint may have added relevance for systemic treatments associated with significant toxicity.
- 5-year survival rate: proportion of patients still alive 5-years after diagnosis.
Comments on the Response and Survival Data
- Response rates vary significantly (e.g. 15-70%) based on disease type and the systemic agent being utilized. The range of median duration of response varies too (e.g. 2-15 months).
- Considering the rapid growth of emerging cancer therapies, obtaining reliable response and survival data for specific cancer types and/or patients is a moving target. Hence, generalist and palliative care specialists should confer with treating oncologists when engaging in advance care planning discussions with cancer patients. They should also empower patients to discuss response rates, median duration of response, survival rates, and toxicity concerns directly with their oncologists.
- Response is typically determined after 2 cycles of treatment (usually one cycle every 21-28 days). Note: patients who progress after 1 cycle will generally continue progressing after two.
- Published cancer data on relevant clinical endpoints usually include mid-point ranges derived from the available clinical trials or combination chemotherapy trials. Specific published data may not be representative of all cancer patients. Instead, it may represent the ‘best case’ outcome, from a population of patients who were in good enough health or have the needed functional capacity to participate in a clinical trial (e.g. ambulatory, spending more than half of their awake day active). Actual responses and response durations for a non-clinical trial population may therefore differ.
- Subsequent chemotherapy following disease progression, can be expected to have a lower response rate and shorter duration of response than first-line chemotherapy.
- Yet, with certain cancer treatments, long positive tails, or outlier results in which patients received much higher than the median survival benefit, may compel patients to pursue additional systemic cancer treatment attempts.
- As noted in Fast Fact #13, for patients with late-stage or metastatic solid tumors with no further antineoplastic treatment options, patient-factors such as performance status, presence of specific symptoms such as dyspnea, and extent of metastatic disease burden are more reliable prognostic factors than the type of cancer.
5-Year Survival Data: The National Comprehensive Cancer Network (NCCN), American
Cancer Society (ACS), and the Surveillance, Epidemiology, and End Results (SEER) Program, all provide free, on-line 5-year survival data that is semi-regularly updated and classified based on cancer type and cancer stage. The data presented in the table below was accessed from these websites in July 2019. For comparison, the overall 5-year survival all cancers regardless of site is 67.1%.
Overall 5-year Survival | 5-Year Survival: Localized Disease (confined to primary site) | 5-Year Survival: Distant disease (metastasized) | |
Bladder | 77.1% | 69.5% | 4.6% |
Breast | 89.9% | 98.8% | 27.4% |
Colon and rectum | 64.4% | 89.9% | 14.2% |
Kidney | 74.8% | 92.5% | 12.0% |
Lung | 19.4% | 57.4% | 5.2% |
Melanoma | 92.2% | 98.7% | 24.8% |
Pancreas | 9.3% | 37.4% | 2.9% |
Prostate | 98.0% | 100% | 30.5% |
Oral Cavity/Pharynx | 65.3% | 84.4% | 39.1% |
Ovary | 47.6% | 92.4% | 29.2% |
Uterus | 81.2% | 95.0% | 16.8% |
References
- DeVita, Hellman, and Rosenberg. Cancer: Principles and Practice of Oncology. 10th Edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2014.
- Waun Ki Hong, et al, eds. Holland-Frei Cancer Medicine. 8th Edition. Hamilton, Ontario: BC Decker; 2010.
- Prasad V, Kim C, Burotto M, et al. The strength of association between surrogate end points and survival in oncology: a systematic review of trial-level meta-analyses. JAMA Intern Med 2015:175(8):1389-1398.
- U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). Guidance for industry: clinical trial endpoints for the approval of cancer drugs and biologics. Published December 2018. Available at https://www.fda.gov/media/71195/download May 2007. Accessed July 10, 2018.
- National Cancer Institute: Surveillance, Epidemiology, and End Results Program. Available at https://seer.cancer.gov/statfacts/ Accessed July 10, 2019
- National Comprehensive Cancer Network: Patient and Cancer Resources. Available at https://www.nccn.org/patients/guidelines/cancers.aspx. Accessed July 10, 2019.
- Cancer Facts and Figures 2019: American Cancer Society. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf. Accessed July 10, 2019.
Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition was edited by Drew A Rosielle and published November 2007. 3rd edition edited with data updates in August 2015. 4th Edition was edited by Sean Marks in July 2019.
Conflicts of Interest: None reported
Authors’ Affiliations: Medical College of Wisconsin; Milwaukee, Wisconsin.
Fast Facts and Concepts are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew A Rosielle MD (University of Minnesota Medical School), with the generous support of a volunteer peer-review editorial board, and are made available online by the Palliative Care Network of Wisconsin (PCNOW); the authors of each individual Fast Fact are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at Palliative Care Network of Wisconsin with contact information, and how to reference Fast Facts.
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