Futile Immunotherapy for Cancer Grows More Common

Providing immunotherapy for patients with metastatic cancer that proves quickly terminal is increasing, with more than 1 in 14 immunotherapy treatments in 2019 initiated within 1 month of death, according to a large retrospective cohort study.

Proportions of patients with metastatic disease who started immunotherapy within 1 month of death rose over the study periods (the time of FDA approval until 2019) from 0.8% to 4.3% for melanoma, 0.9% to 3.2% for non-small cell lung cancer (NSCLC), and 0.5% to 2.6% for kidney cell carcinoma.

By 2019, these end-of-life–initiated treatments represented 7.3% of all immunotherapy treatments, reported Sajid A. Khan, MD, of the Yale School of Medicine in New Haven, Connecticut, and colleagues.

Moreover, the study showed that this practice is more common at non-academic and lower-volume health care centers, and that these types of facilities have worse survival rates.

“The rate of end-of-life–initiated immunotherapy is increasing,” Khan and colleagues wrote in JAMA Oncology. “More research on the benefit and value of these therapies in patients with advanced-stage disease is needed.”

Their study covered 242,371 patients from the National Cancer Database: 20,415 with melanoma, 197,331 patients with NSCLC, and 24,625 patients with kidney cell carcinoma, all at stage IV.

Patients’ mean age was 67.9, with 42.5% older than 70; 56.0% were men, and 29.3% received immunotherapy

Study periods for each cancer type started the year immediately following FDA approval of the first immune checkpoint inhibitor for the treatment of stage IV disease for that particular indication (2012 for melanoma, and 2016 for NSCLC and kidney cell carcinoma).

Khan’s group found that, when stratifying by facility type and volume, fewer patients treated at academic and high-volume facilities started immunotherapy at the end of life for all three cancer types. And survival on immunotherapy at these institutions was significantly better: odds of death within 1 month of starting immunotherapy were lower by 31% at an academic or high-volume center (OR 0.69, 95% CI 0.65-0.74, P<0.001) versus a non-academic facility, and by 30% (OR 0.70, 95% CI 0.65-0.76, P<0.001) relative to very low-volume centers.

Across all three cancer types, those patients with three or more organs involved in metastatic disease were 3.8-fold more likely (95% CI 3.1-4.7, P<0.001) to die within 1 month of immunotherapy initiation than those with lymph node involvement only.

Khan and colleagues also found that patients with advanced disease treated at high-volume and academic facilities had longer survival compared with those treated at very low-volume or non-academic centers, regardless of whether or not they received immunotherapy, with overall risk-adjusted mortality rates lower by 10%-33%.

In an editorial accompanying the study, Michael Hoerger, PhD, of Tulane University in New Orleans, and two colleagues highlighted the study’s finding that treatment with immunotherapy was associated with a 5%-18% absolute increase in 5-year survival across the three cancer types. But academic centers had 5%-9% better absolute 5-year survival than non-academic centers, and high-volume health care centers had 4%-13% better absolute survival than very low-volume centers.

Furthermore, Hoerger and colleagues suggested that since “academic and high-volume centers may be referred more complex cases,” these figures may underestimate the survival gap.

“These health care center associations with survival are profound,” the editorialists wrote. “These differences in immunotherapy use and patient survival can be understood through a systemic health care disparities lens. Patients who are experiencing health care disparities may be undertreated early in the disease course due to barriers to access and utilization and may also receive interventions less likely to offer benefit near death. [The findings in this study] fit that pattern.”

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