The Forgotten Importance of Quality of Life in Cancer and Clinical Trials

Author: Christopher Gregg CSO: Storyline Health and Primordial AI , Instructor of the Uncharted Cancer Patient Masterclass .

Most cancer research focuses on the tumor cells and we are neglecting the patient experience.

Drug companies make drugs aimed to kill cancer, but are often detrimental to the patient’s health and quality of life. This is a problem and an opportunity.

The reality of being a cancer patient is scary. Nausea, bone pain, gut pain, hair loss, inflamed eyes, mouth sores, weakness, brain fog, muscle pain, depression, anxiety, diarrhea, and extreme fatigue become part of daily life. Moreover, drug toxicity often contributes to death, as blood system, liver and kidney damage add up over time due to toxicity, reaching levels that require the patient to stop treatment or even contribute to death.

As a patient, treatment toxicity is something I worry a lot about. Fundamentally, the point of optimal disease control for any given cancer patient exists at a fulcrum that optimally balances tumor cell killing and patient health.

All of this means that there is an opportunity to develop treatments that only aim to improve patient quality of life without any improvement to overall survival or time to progression.

A clinically successful drug only needs to extend median overall survival by >2.5 months compared to the standard of care. However, efforts to develop treatments that improve quality of life as a primary clinical trial endpoint are lacking.

As a scientist and researcher, I am struck by how the clinical trial ecosystem focuses on overall survival and time to progression, but not quality of life. There is a large opportunity and unmet need here.

Cancer symptom responses and patient quality of life are only barely starting to be considered as primary endpoints for cancer clinical trials 1–3. Importantly, typical clinical endpoints, including overall survival, progression free survival, and response rate do not fully capture the clinical risks or benefits of a treatment 1–3. For this reason, composite scores that integrate patient PROs (patient reported outcomes) and better assess total clinical benefit have been used as clinical endpoints in some cases. For example, a composite clinical benefit response score was used in the approval of gemcitabine for pancreatic cancer 4. Thus, symptom, behavioral, and mental health phenotypic data can be incorporated into a composite score with complete response rate and progression-free survival metrics to evaluate the success of clinical trials. More of this could both improve the patient experience and create new opportunities for value creation in biotech and pharma.

It is essential to objectively measure how therapeutic regimens affect patient symptoms, quality of life, mental health, and cognitive functioning. If a therapy offered the same overall survival as standard care, but improved quality of life, then the approach would nevertheless be a success and be positioned to dominate the marketplace. Currently, long-term cancer survivors face challenging short- and long-term mental health issues 11,12. Patients contend with the anxiety and fear of recurrence or progression, difficulties managing pain, sleep problems, nausea, neuropathy, sexual functioning, cognitive impairment, and other problems. Cancer survivors are more than twice as likely to have disabling mental health problems compared to adults without cancer, and they are nearly 6 times more likely if cancer is co-morbid with other illnesses 11. Variable cognitive changes can occur in response to different treatments (chemobrain) 29, and inflammatory cytokines in cancer patients may also contribute to cognitive and behavioral changes 30.

Overall, as treatments continue improve survivorship, technologies and approaches to research, monitor, improve, and manage patient quality of life are urgently needed.

Objective measures of quality of life that enable robust primary endpoints for clinical drug trials are a missing piece and should be a federally mandated NIH priority.

References

1. Bouchard, L. C., Aaronson, N., Gondek, K. & Cella, D. Cancer symptom response as an oncology clinical trial end point. Expert Rev. Qual. Life Cancer Care 3, 1–12 (2018).

2. Secord, A. A. et al. Patient-reported outcomes as end points and outcome indicators in solid tumours. Nat. Rev. Clin. Oncol. 12, 358–370 (2015).

3. Wilson, M. K., Karakasis, K. & Oza, A. M. Outcomes and endpoints in trials of cancer treatment: the past, present, and future. Lancet Oncol. 16, e32–e42 (2015).

4. Burris, H. A. et al. Improvements in Survival and Clinical Benefit With Gemcitabine as First-Line Therapy for Patients With Advanced Pancreas Cancer: A Randomized Trial. J. Clin. Oncol. 41, 5482–5492 (2023).

About the author: Christopher Gregg PhD is a tenured Professor of Neurobiology and Adjunct in Human Genetics at the University of Utah, and the Chief Science Officer and Co-founder of Storyline Health , Primordial AI , and Uncharted Cancer Patient Masterclass .

A leader in genomics, evolution, metabolism, data science technologies, and computational analyses of natural behavior. Recipient of the Eppendorf & Science Prize in Neurobiology, the NYSCF Robertson-Neuroscience Investigator award. Work selected as a top breakthrough of the year by the NIMH in 2010 and again in 2018 by STAT. Committed to developing precision medicine solutions that radically improve patient care.

He is also a stage IV cancer patient.