Overuse of Immunotherapy in Patients Near the End of Life

Immunotherapy is a promising development in cancer treatment. Could it, however, be overused in some situations, particularly near the end of life? This is an important question when reassessing its role in cancer care.

Rare but Remarkable Success Stories

When a patient does not respond to chemotherapy, immunotherapy may offer hope. For example, we know that some patients with advanced cancer whose tumors have particular genetic characteristics, such as TMB-H, MSI-H , can respond well and durably to immunotherapy despite not responding to chemotherapy. Such successes make immunotherapy appealing and may prompt patients and doctors to think, “Why not?”

However, this hopeful approach may lead to overuse near the end of life. We see immunotherapies used in settings without FDA (United States Food and Drug Administration) approval or adequate data, such as metastatic ovarian cancer.

Facing the Facts

Miraculous immunotherapy outcomes near the end of life are rare, and it is currently impossible to predict clearly who will respond this way. Although immunotherapies generally cause fewer adverse effects than chemotherapy, it is important to remember that severe and life-threatening immunotherapy-specific adverse effects can also occur.

In an example reported by Dr. Laura Petrillo of Massachusetts General Hospital, a 95-year-old woman with metastatic cancer died in hospital from complications of severe immunotherapy-induced colitis . Although such severe reactions are rare, even milder adverse effects can diminish quality of life.

Even when adverse effects are relatively limited, receiving immunotherapy may mean spending precious time in hospital for infusions rather than at home. These patients are also often not referred to hospice (end-of-life palliative care centers) and die in hospital. Cost is another major concern: a treatment cycle can cost up to 20 thousand dollars in the United States (3-5 thousand dollars in Turkey), creating financial difficulties.

On January 4, 2024, JAMA Oncology published a study providing important data on this issue.

Key Findings

1. Rates of Immunotherapy Initiation in the Final 30 Days: Among patients with stage IV melanoma, lung cancer, and kidney cancer, immunotherapy initiation in the last 30 days of life increased four- to fivefold.

2. Patients Who Died Within the Last 30 Days:

   • In melanoma, the proportion receiving immunotherapy rose from 0.8% to 4.3%.
   • In NSCLC (non-small cell lung cancer), it rose from 0.9% to 3.2%.
   • In renal cell carcinoma, it rose from 0.5% to 2.6%.

3. Survival Among Patients Starting Immunotherapy:

   • Of the 71 thousand participants, 5192 (7.3%) died within the first 30 days after starting immunotherapy.
   • A further 66 thousand patients (92.7%) survived beyond 30 days.

4. Survival by Performance Status:

   • Median survival was 14.3 months in patients with an ECOG performance score of 0-1, compared with only 4.5 months in those with a score ≥2.

Immunotherapy Should No Longer Be Left Until Last

Immunotherapies are no longer merely a last resort and are now generally used as first-line treatment. This improves the cost–benefit balance and helps reduce inpatient immunotherapy use. However, for immunotherapy and other innovative treatments to succeed, genomic tests are crucial for identifying the patients most likely to benefit.

With all these uncertainties and challenges, guiding patients appropriately remains difficult. Shared decision-making between patient and doctor is essential. When considering immunotherapy, a broader perspective is needed rather than focusing only on stories of exceptional outcomes. Just because a treatment can be given does not mean it always should be.