Deborah Doroshow, MD, on the Disappointments Uncovered About Inpatient Immunotherapy

Cancer patients receiving care as inpatients who are started on in-patient immune checkpoint inhibitors (ICIs) unfortunately generally do not live long enough to reap the benefits of the drugs, researchers reported.

A team from four major academic institutions conducted an inpatient immunotherapy outcomes study designed to describe the characteristics and outcomes of 159 patients, median age of 61, receiving ICIs as inpatients -- the largest such examination to date.

In the following interview, Deborah B. Doroshow, MD, of the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York City, reviewed the team's findings, which were presented at ASCO's Quality Care Symposium.

What does the study add to the literature?

Doroshow: Over time, we have been using ICIs more toward the end of life, and we observed that patients were starting ICI therapy while they were inpatients. Many of these patients were very ill and ended up dying soon after starting inpatient ICI treatment.

We set out to find how often ICIs are used in an inpatient setting, why patients were getting them, and how they fared once they were on inpatient ICI therapy. The existing literature was primarily single-institution studies. We conducted the largest and first multi-institutional examination of outcomes.

The data are sobering. Patients were receiving ICIs for a variety of reasons. Most patients (73%) started ICI therapy in the inpatient setting as opposed to continuing as outpatients for numerous types of cancers -- most commonly thoracic (26.4%) and gastrointestinal (19.5%) cancers. More than three-quarters had metastatic solid cancers, a small number had locally advanced tumors, and some had hematologic malignancies. Almost 75% had private insurance or Medicare, and 18.2% had Medicaid.

There were two take-always from the study: 27% of patients died during hospitalization while they received inpatient ICI therapy, which is quite striking. The median overall survival (OS) from the first dose of inpatient therapy was only 47 days, suggesting that those who received inpatient ICIs were not living long enough to reap the benefits of these drugs. The drugs were used as a "Hail Mary" in a challenging situation.

We also found that patients were typically less robust and frail, and therefore less likely to benefit from anticancer therapy. Most patients who have advanced solid tumors are treated in an outpatient setting. When admitted to the hospital, they are usually quite ill and have a poor prognosis. This is a very sick population of patients, so it's not surprising the median OS was so brief.

What is the significance of the finding that nearly half of the ICIs given did not have FDA approval for that cancer type and stage at the time of administration?

Doroshow: This represents a last-ditch effort. Patients received ICIs for types of cancer that do not have FDA approval, such as multiple myeloma. Oncologists may have seen presentations of results in an international setting and began using these drugs prior to FDA approval. This was seen more in the early part of the study.

Anecdotally, we found a clear difference in inpatient ICI use from the beginning to the end of the 2010s. This may reflect usage while ICIs were being studied for diseases. Negative studies for ICIs in multiple myeloma appeared in the 2020s.

Based on the data, which patients would be the best candidates for inpatient ICI therapy?

Doroshow: We are looking into this, and are adding a group of patients from Stanford to expand our cohort to more than 200 patients. A statistician is analyzing predictors of who may derive more or less benefit from inpatient ICI therapy. It may be possible to identify factors that predict longer survival and more benefit.

In the current retrospective study, however, few patients benefited from treatment or had cancer shrinkage, and few clinicians noted that patients improved as a result of inpatient ICI treatment. In some institutions this practice is disallowed, and in others physicians need special permission. Originally, the rationale for that was financial, but there may be clinical and ethical rationales not to give in-patient immunotherapy.

How do you plan to determine predictors of overall survival and discharge to home?

Doroshow: We have a statistician/oncologist doing univariate and multivariate analyses to look at clinical and demographic characteristics. We also had excellent feedback at the ASCO Quality Care meeting about specific questions, such as whether patients had been seen by a palliative care service prior to receiving inpatient ICI therapy. We'll go back and look at patient charts.

What's your bottom-line message?

Doroshow: Be very wary about the use of inpatient ICIs, especially when the patient is just starting a new therapy. It takes weeks to months to induce clinical benefit. For patients who are frail or have a short survival prognosis, the likelihood of benefit is low.

Read the study here.