Immunotherapy for Metastatic Cancer on the Rise, Even Near End of Life

Sajid A Khan, MD, FACS, FSSO

More and more people living with cancer are being prescribed immunotherapy as an effective treatment option. But can it be administered too late? A new study led by Yale Cancer Center researchers at Yale School of Medicine found that while the initiation of immunotherapy near the end of life has increased over time, a closer look at the benefit and value of these therapies in patients with advanced-stage disease is needed.

The findings were published in JAMA Oncology on Jan. 4.

“Immunotherapy has revolutionized the field of oncology over the last decade,” said Dr. Sajid Khan, senior author of the study and section chief of hepato-pancreato-biliary (HPB) and mixed tumors at Yale School of Medicine. “Because survival is substantially improved for many patients treated with these drugs, its overall application has increased across the United States.” Still, Kahn says, the data suggest that providers should be more discerning between cases where immunotherapy can extend life and those where it can’t.

“Our study found that in the last 10 years, the initiation of immunotherapy in [what turned out to be] the final month of a patient’s life has significantly increased, accounting for one in 14 immunotherapy treatments overall,” said Khan, a member of Yale Cancer Center and the co-director of team science at Yale Center for Clinical Investigation. In this retrospective study, researchers looked specifically at a dataset of patients who were prescribed immunotherapy within the last 30 days of life; patients who survived longer as a result of immunotherapy were not part of the study.

The study showed that the majority of patients with these advanced cancers—melanoma, non-small cell lung, and renal cell carcinoma—were not prescribed immunotherapy at all. It focused on the 2-3% of all patients considered in the study who received the treatment within the last 30 days of life.

“The reason we focused on immunotherapy initiation at the end of a patient’s life with cancer metastasis was to see what we could learn about prescribing patterns,” said Kahn. “What we found we hope will serve as a harbinger for shifts in the clinical approach to patients with advanced cancer.”

Immunotherapy effective for many – but not if begun too late

Researchers say it’s important to note that most patients with late-stage cancer are prescribed immunotherapy earlier and do not die within 30 days of starting the treatment, and that patients with co-morbid conditions, in addition to cancer, are less likely to have good results with immunotherapy. That’s important to know because, according to Khan, one dose of immunotherapy costs $10,000 to $20,000 dollars. So, starting immunotherapy at the end of life not only can be ineffective from a cancer survival perspective but also costly.

The study included 20,415 stage IV metastatic melanoma patients,197,331 stage IV non-small cell lung cancer patients (NSCLC), and 24,625 stage IV renal cell carcinoma (RCC) patients treated with immune checkpoint inhibitors from 2012 to 2019 for metastaic melanoma patients and from 2016 to 2019 for NSCLC and RCC patients. Researchers considered each patient’s age, sex, race, and ethnicity as well as the location of metastases and the type of medical facility where treatment was given. They found that in 2019 these end-of-life-initiated (EOL-I) treatments represented 7.3% of all immunotherapy treatments.

Improved survival outcomes when immunotherapy is administered at academic, high-volume cancer hospitals

According to the researchers, the approach of giving immunotherapy to patients with co-morbid conditions was used more frequently at non-academic and low-volume hospitals, and “there were improved survival outcomes when the therapy was administered at academic and high-volume facilities,” said Khan, potentially because they are more experienced at mananaging severe immune-related and other adverse events or that their multidisciplinary teams evaluate and start patients on treatment more expediently and with careful scrutiny to co-morbid conditions. As a result, while patients treated at non-academic or low-volume hospitals had higher odds of receiving immunotherapy at end of life, patients were less likely to experience death at academic and high-volume hospitals when given immunotherapy for metastatic cancers, the study found.

The researchers note that immunotherapy does provide a strong overall survival benefit for patients with metastasis – even those in high-risk sub-groups. “But the outcome for patients receiving immunotherapy towards the end of their life was different, depending on the burden of metastasis,” said Khan. Patients with more than three sites of distant metastases are less likely to benefit from immunotherapy initiation than those with only distant lymph node metastasis, he said.

The study findings highlight the need for further investigation into the implications of immunotherapy given at the end of life with the hope of refining treatment guidelines for patients with metastatic cancer.

Daniel Kerekes from Yale School of Medicine and Yale Department of Surgery was the study’s first author. Alexander Frey, Elizabeth Prsic, Thuy Tran, James Clune, Mario Sznol, Harriet Kluger, Howard Forman, Robert Becher, and Kelly Olino were Yale co-authors.