Older and multimorbid patients are excluded and undertreated
Most people with cancer are over 65 but most trial patients are younger and fitter. We guess how to treat the majority.
More than half of cancers and most cancer deaths occur in people over 65, yet older adults have been under-represented in registration trials for decades, and those enrolled are fitter than the general older population. Frailty, renal and hepatic function, polypharmacy, cognitive impairment and competing causes of death all change the balance of benefit and harm, but they are rarely measured in trials or in clinics, so older patients are both over-treated (full-dose regimens they cannot tolerate) and under-treated (denied curative therapy on the basis of age alone). Geriatric assessment with management is proven in randomised trials to cut severe toxicity by a fifth or more without compromising survival, and is recommended by ASCO, yet it is done in a minority of clinics. Age-specific dosing, endpoints that capture function and independence, and trial designs that include the patients who actually get cancer are the gap.
- Eligibility criteria on organ function and performance status exclude many older patients from trials.
- Sponsors prefer younger, fitter populations to maximise the apparent effect and minimise toxicity signals.
- Chronological age is used as a proxy for fitness in clinical decisions instead of measured frailty.
- Geriatric assessment takes time and is not reimbursed in most systems.
- Trial endpoints (progression-free survival, response) do not capture what matters most to older patients: function, independence and cognition.
- GAP70+ and GAIN randomised trials showed geriatric assessment-guided management reduces severe toxicity, and the ASCO geriatric oncology guideline (2018, updated 2023) recommends it for all patients aged 65 or older receiving systemic therapy.
- FDA guidance on inclusion of older adults in cancer clinical trials (2022) encourages removal of age-based exclusions and enrolment of the very old.
- NIH's Inclusion Across the Lifespan policy (2019) requires justification for any age-based exclusion.
- The Cancer and Aging Research Group (CARG) provides validated toxicity prediction tools and runs trials designed for older adults.
- The International Society of Geriatric Oncology (SIOG) publishes age-specific treatment recommendations.
- Venetoclax-based and other lower-intensity regimens (VIALE-A in AML, CLL14 in CLL) were developed specifically for patients unfit for standard therapy.
People with dementia who develop cancer are often either overtreated or written off, and decisions are made without them. A clear pathway for assessment, consent and treatment planning would improve both.
Most people with cancer are over 65, but trials mostly enrol younger, fitter people. Requiring a group of older patients, assessed for frailty, in every big trial would show whether the drug works and is safe for those most likely to receive it.
Errors happen when patients move from hospital to home, from surgery to chemotherapy, or from oncology back to their family doctor. A short standard checklist and a pharmacist medication review at each move would prevent many of them.
Most people with cancer are over 65, but most trial patients are younger and fitter. A dedicated fund would pay for trials designed for the patients we actually treat.
Drugs are approved on trials of fit, younger patients and then given to everyone. A required follow-on trial in older, sicker and more diverse patients would show whether the benefit holds in real life.
Frailty is the strongest predictor of who will be harmed by treatment, but it is rarely measured. Software can estimate it automatically from existing records and flag patients who need a closer look.
Hormone-blocking treatments for prostate and breast cancer, taken for years, raise the risk of diabetes, heart disease and bone fractures. Survivors on these drugs should get the same preventive care as diabetics.
Older cancer patients depend on family carers who receive no training or support. Paying for carer training and short breaks would keep patients at home and out of hospital.
Trials usually take only patients who are up and about most of the day. Those who spend more time resting, a common group in real clinics, are excluded, so nobody knows how to treat them. A dedicated group in each trial would answer that.
The dose for a frail 80-year-old is guessed from what fit 55-year-olds tolerated. Running dose-finding in older patients directly, using frailty assessment, would give doses they can actually take.
Family doctors often do not know who is responsible for a cancer patient's blood pressure, diabetes or new symptom. Written agreements plus a same-day electronic question line to the oncologist would fill the gap.
Most cancer patients are over 65, yet treatment is chosen by age and guesswork and trials exclude them. Assess fitness properly and design trials that include real older patients.
A short structured check of memory, mobility, nutrition and medicines before treatment cuts serious side effects in older patients without reducing benefit. It should be automatic, not optional.
When a geriatrician helps manage older patients around the time of a cancer operation, complications, delirium and hospital stays fall. This should be standard for anyone over 75 having major cancer surgery.
For frail older patients, the journey to hospital can be the hardest part of treatment. Nurses can safely give some cancer treatments at home, which may help more people complete their course.
Frail women over 80 with small hormone-sensitive breast cancers may do as well with a daily tablet as with surgery. A trial would define who can safely avoid the operation.
Many hospital stays for cancer patients, such as for fever after chemotherapy in low-risk cases, could be delivered at home with daily nurse visits and remote monitoring, which patients prefer and which is cheaper.
Dosing advice for people with weak kidneys or liver is often missing at approval and added years later, if ever. Requiring those studies before approval would protect a large group of real-world patients from day one.
Most cancer patients are over 65 and many have other illnesses, yet trials routinely exclude them. Regulators should require sponsors to justify each exclusion, so the evidence matches the patients.
Older, frailer and sicker patients are usually kept out of trials but make up most of those treated. Require companies to report how these patients do in practice.
A few weeks of exercise, nutrition and mental preparation before a big operation helps older patients recover faster and with fewer complications. It costs little and should be routine.
Instead of excluding sicker patients entirely, trials would run a side group for them, receiving the new drug with closer monitoring, so we learn how it behaves in the people who will actually get it.
Cancer pills interact with many common medicines for heart, stomach and blood conditions, sometimes dangerously. A pharmacist check before starting, and at each refill, would prevent avoidable harm.
For a frail 80-year-old, staying independent may matter more than living a few months longer. Trials designed for older patients should measure what they care about.
Most trials use the same blood-test cut-offs for kidney and liver function regardless of how the drug is cleared from the body. Setting the cut-off from the drug's own pharmacology would let many more people join safely.
A treatment that adds two months of life but takes up most of those days in hospitals and clinics may not be worth it to an older patient. Trials should report how many days treatment consumes.
New cancer drugs are approved on trials of younger, fitter patients, then given mostly to older ones. Regulators should require real-world safety and benefit data in the over-75s and put it on the label.
Screening someone unlikely to live ten years causes harm without benefit. A life-expectancy estimate in the medical record could stop invitations and prompt a conversation.
Older cancer patients often take ten or more medicines, some of which no longer help and may interact with cancer treatment. A pharmacist review to stop unnecessary ones, at diagnosis and when goals change, would reduce harm.
Most cancer patients are older and have other illnesses, but nearly all animal experiments use young healthy mice. Results may not transfer.
Frail older patients are often given full doses and then have them cut after bad side effects, or are given nothing. Trials should test starting at a lower dose from the beginning.
Most kidney tumours under 3 cm found by chance grow slowly and a fifth are benign. Watching them, with surgery only if they grow, could spare many operations.
Older patients are more likely to be harmed by standard-dose chemotherapy, and a structured assessment of function, cognition, nutrition and social support lets oncologists adjust treatment safely. Starting lower does not appear to shorten life. Most older patients still do not get such an assessment.
VIALE-A turned a palliative regimen into one that produces remission in two-thirds of older AML patients and is now the reference treatment for anyone not fit for intensive chemotherapy. It shifted the field towards lower-intensity targeted combinations and opened the door to adding FLT3, IDH and menin inhibitors to the backbone. Cure remains uncommon and most patients relapse within two years.
CLL14 established the first chemotherapy-free, fixed-duration regimen for front-line CLL and made MRD-guided thinking mainstream in the disease. Patients get a year of treatment and then a treatment-free period rather than indefinite therapy. The choice today is between fixed-duration venetoclax combinations and continuous BTK inhibitors, with no proven survival difference.
MAIA made a daratumumab-based triplet the standard first treatment for older or frail myeloma patients, replacing Rd alone. It proved an anti-CD38 antibody could improve survival, not just delay progression, when used up front. Quadruplets built on this backbone are now being tested in the same population.
Many older people carry blood clones one or two steps from leukaemia, and those clones also drive heart disease through inflammation. CHIP is why blood-based cancer tests must filter out mutations from blood cells, and it opens a route to preventing both leukaemia and cardiovascular events in carriers.
Pages like this
not linked directly; found by shared links- BottleneckTrials do not represent the people who get cancer
Shares Parallel real-world cohorts for sicker patients alongside every pivotal trial, A mandatory over-70s cohort with geriatric assessment in every pivotal trial, Make sponsors justify every trial exclusion of older and multimorbid patients, Geriatric assessment by default for every older patient, and trials that admit them.
- BottleneckWrong doses
Shares A mandatory over-70s cohort with geriatric assessment in every pivotal trial, Kidney and liver impairment dosing studies completed before approval, not years after, Shorter venetoclax courses in unfit AML, Dose-finding in older and frail patients, not extrapolation from fit ones.
- BottleneckToxicity and quality of life are undervalued
Shares A standard handoff with medication reconciliation at every cancer care transition, Hospital-at-home for oncology: treating low-risk febrile neutropenia and dehydration at home, Structured deprescribing review at cancer diagnosis and again at transition to palliative care, Geriatric assessment by default for every patient over 70 starting cancer treatment.
- BottleneckFragmented care and guideline gaps
Shares Formal shared-care agreements between oncology and family doctors, with same-day e-consult, A standard handoff with medication reconciliation at every cancer care transition, A defined pathway for patients with both dementia and cancer, Home administration of selected chemotherapy and immunotherapy for older and frail patients.
- TargetBCL-2
Shares VIALE-A, CLL14, VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy, CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients.
- CompanyAbbVie (incl. ImmunoGen, Capstan)
Shares VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy, CLL14: one year of venetoclax plus obinutuzumab instead of chemo-immunotherapy in older, less fit CLL patients, Venetoclax, Chronic lymphocytic leukaemia.
- TermTumour lysis syndrome (TLS)
Shares VIALE-A, CLL14, Venetoclax, Chronic lymphocytic leukaemia.
- BottleneckCachexia, toxicity and the limits of the patient
Shares European Society for Clinical Nutrition and Metabolism, Multinational Association of Supportive Care in Cancer, Cardio-oncology, Geriatric assessment.