Highlight
– Use of systemic anticancer therapy (SACT) in the last 30 days of life increased in Ontario between 2015 and 2020, driven predominantly by immunotherapy.
– Among 68,963 adults who died with cancer (2015–2021), 26.6% received SACT in the last 30 days of life.
– Receipt of any SACT at the end of life was associated with substantially greater odds of high health services use (multiple ED visits or hospitalizations, or any ICU admission) and hospital death; adjusted odds ratios varied by SACT type but were elevated for chemotherapy, immunotherapy, targeted agents, and combination therapy.
Background
Over the last decade oncology practice has been transformed by targeted therapies and, particularly, immune checkpoint inhibitors. These agents have improved survival and quality of life for many patients with advanced cancers, and their expanding indications and perceived tolerability have encouraged broader use. However, use of systemic anticancer therapy (SACT) close to the end of life (EOL) remains controversial. Historically, administration of cytotoxic chemotherapy in the last weeks of life has been considered a marker of aggressive, low-value care because it is associated with worse symptom burden, more intensive health services use, and fewer hospice referrals.
Most guidelines and quality frameworks (for example, national quality metrics that track chemotherapy within 14–30 days of death) were established before the immunotherapy and targeted therapy eras. These novel agents have different toxicity profiles, patterns of benefit, and timelines to response, which complicates simple application of historic EOL chemotherapy metrics. The study by Iqbal et al. (J Clin Oncol. 2025) provides timely, population-level data on how the evolving SACT landscape affects EOL care patterns and health services use.
Study design
Iqbal and colleagues performed a population-based analysis using the Ontario Cancer Registry and provincial administrative health data. The cohort included adults with solid tumors or hematologic malignancies who died between March 2015 and March 2021 and had been diagnosed within five years of death. Receipt of SACT in the last 30 days of life was classified into four mutually exclusive categories: chemotherapy alone, chemotherapy plus immunotherapy, immunotherapy alone, and targeted therapy alone. Outcomes were measures of high health services use in the last 30 days of life—defined as ≥2 emergency department (ED) visits, ≥2 hospitalizations, or any intensive care unit (ICU) admission—and death in hospital. The authors used segmented linear regression to estimate temporal trends and multivariable logistic regression to estimate adjusted odds ratios (aORs) for outcomes associated with SACT types, adjusting for demographic and clinical covariates.
Key findings
Population and exposure. Of 68,963 patients who met inclusion criteria, 18,337 (26.6%) received systemic anticancer therapy within the last 30 days of life. Use of SACT at the EOL rose significantly between March 2015 and March 2020 at an average rate of 0.072% per month (P < .001), largely driven by an increase in immunotherapy alone (0.064% per month; P < .001).
Association with high health services use and hospital death
Receiving any SACT in the last 30 days of life was associated with markedly higher odds of high health services use and hospital death compared with not receiving SACT. The authors report the following adjusted odds ratios (aORs) for the two outcomes (high health services use and hospital death, respectively):
- Chemotherapy alone: aOR 2.20 (high services use) and 2.72 (hospital death)
- Chemotherapy + immunotherapy: aOR 2.36 and 3.10
- Immunotherapy alone: aOR 1.92 and 2.27
- Targeted therapy alone: aOR 1.75 and 2.37
These associations were consistent across SACT types—although magnitude varied—with combination chemo‑immunotherapy associated with the highest odds of hospital death. In other words, patients receiving SACT in the last month of life were roughly two- to three-fold more likely to experience intensive, hospital-based care and to die in hospital than those who did not receive SACT.
Temporal trend nuance
The rise in EOL SACT use was concentrated in the period before the COVID-19 pandemic (March 2015–March 2020). The accelerated adoption of immunotherapy during this period likely reflects expanding approvals and clinician comfort with these agents for multiple tumor types.
Expert commentary and interpretation
The Iqbal et al. study provides robust, population-level evidence that contemporary SACT—whether conventional chemotherapy, targeted agents, immunotherapy, or combinations—when given in the last month of life is associated with substantially greater health services use and in-hospital death. This association has several plausible drivers.
First, SACT near EOL may be a marker of aggressive care choices and unmet palliative needs. Patients and clinicians often pursue systemic therapy in hopes of disease control, symptomatic benefit, or life prolongation; yet, when benefit is unlikely, therapy can prolong the dying process, increase toxicity risk, and prompt emergency visits and hospital admissions.
Second, immunotherapy has a unique toxicity spectrum—immune-related adverse events (irAEs)—which can present unpredictably and sometimes require hospitalization or ICU-level care (e.g., severe pneumonitis, myocarditis, colitis). Such toxicities can occur rapidly and be difficult to distinguish from disease progression, particularly late in illness, driving more hospital-based care.
Third, prognostic uncertainty complicates decision-making. Novel agents sometimes produce dramatic responses even late in disease for a minority of patients, and clinicians may reasonably attempt therapy in the face of uncertain life expectancy. However, population-level data show that when SACT is given broadly near EOL, aggregate health services use and hospital deaths increase.
Clinical implications
These findings support several pragmatic actions for oncology practice and health systems:
- Explicitly incorporate novel SACTs into EOL care quality metrics and guidelines. Historic metrics that focused on cytotoxic chemotherapy should be updated to include immunotherapy and targeted agents when assessing potentially aggressive care at the EOL.
- Prioritize early and routine goals-of-care discussions and advance care planning, especially when initiating or continuing SACT in advanced disease. Conversations should address realistic benefits, timelines to response, potential toxicities (including irAEs), and thresholds for discontinuation.
- Integrate palliative care earlier. Randomized evidence (e.g., Temel et al., NEJM 2010) shows that early palliative care in metastatic cancer improves quality of life and may reduce aggressive EOL care. Embedding palliative care alongside active oncology care can help align treatment with goals and reduce unwanted hospital-based interventions.
- Develop decision aids and stopping rules. Multidisciplinary consensus on clinical scenarios where SACT is unlikely to provide benefit (for example, poor performance status, rapid functional decline) and clearer discontinuation criteria could reduce low-value use near EOL.
Limitations and considerations
Interpretation of observational administrative data must acknowledge limitations. Key limitations include potential confounding by indication (patients receiving SACT near EOL may differ in unmeasured ways from those who do not), lack of granular clinical data (for example, performance status, symptom burden, patient and family preferences, and explicit goals-of-care documentation), and inability to distinguish hospital admissions due to treatment toxicity versus disease-related complications. The temporal association between SACT use and increased hospital-based care does not prove causation for individual patients. Nevertheless, the consistency and magnitude of associations across SACT types in a large, population-based sample are concerning and clinically meaningful.
Research and policy gaps
Important next steps include:
- Prospective studies and pragmatic trials testing interventions to align SACT use with patient goals near EOL (for example, early palliative care integration, shared decision-making tools, or clinician decision supports).
- Work to identify biomarkers or clinical predictors that reliably identify patients likely to benefit from late-line SACT, including immunotherapy, to reduce futile exposure.
- Updates to quality metrics to explicitly include immunotherapy and targeted therapies in EOL appropriateness measures, with careful risk adjustment to avoid penalizing appropriate individualized care.
- Health system interventions to minimize avoidable hospital-based care—such as outpatient infusion reaction pathways, rapid-access palliative services, and community-based acute care alternatives.
Conclusion
Iqbal et al. provide compelling population-level evidence that the use of systemic anticancer therapy in the last 30 days of life increased through 2020, largely driven by immunotherapy, and that receipt of SACT at the EOL—regardless of drug class—is associated with higher rates of emergency visits, hospitalizations, ICU admission, and in-hospital death. Clinicians and policymakers should update EOL care frameworks and quality metrics to include novel agents, and oncology teams must emphasize prognostic transparency, shared decision-making, and timely palliative care integration to ensure that treatment near the end of life reflects patients’ goals and minimizes unnecessary hospital-based burden.
Funding and clinicaltrials.gov
See the original publication for detailed funding disclosures and any trial registration information: Iqbal J, et al. J Clin Oncol. 2025;43(30):3279-3291. doi:10.1200/JCO-24-02816. PMID: 40466035; PMCID: PMC12527759.
Selected references
1. Iqbal J, Moineddin R, Quinn KL, et al. Novel Systemic Anticancer Treatments and Health Services Use at the End of Life Among Adults With Cancer. J Clin Oncol. 2025 Oct 20;43(30):3279-3291. doi:10.1200/JCO-24-02816. PMID: 40466035; PMCID: PMC12527759.
2. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non–small-cell lung cancer. N Engl J Med. 2010 Aug 19;363(8):733-742. doi:10.1056/NEJMoa1000678. PMID: 20303747.
3. American Society of Clinical Oncology. Integration of palliative care into standard oncology care: ASCO clinical practice guideline update (see original guideline for full reference and recommendations).
For clinicians: consider the individualized balance of potential benefit and harms when considering SACT near the end of life; document goals-of-care discussions; and involve palliative care early when prognosis is limited or uncertain.
