Increasing Use of Oral Anticancer Agents Raises EOL Care Considerations in RCC

The introduction of new treatment modalities for patients with renal cell carcinoma (RCC) has necessitated a renewed focus on end of life (EOL) care, according to investigators of a recent study in JCO Oncology Practice.^1,2

Hannah E. Dzimitrowicz, MD

Study authors found that patients with metastatic RCC (mRCC) receiving oral anticancer agents (OAAs) and younger patients experienced more aggressive EOL care.¹

After assessing EOL data from 410 mRCC decedents in the University of North Carolina’s Cancer Information and Population Health Resource (CIPHR) and 1508 decedents in SEER-Medicare database, investigators determined that prior OAA use was linked to an increase in systemic therapy treatments in the last 30 days of life. Among individuals included in these databases, 53.4% (n = 219) and 43.5% (n = 656) had received OAAs, respectively.

Systemic therapy was given during the last 30 days of life for 26.5% vs 11.0% of patients who did and did not receive prior OAA therapy in the CIPHR group (P < .001), and 23.4% vs 11.7%, respectively in the SEER-Medicare group (P < .001).

Prior OAA use was also linked to an increase in in-hospital death in CIPHR, and an increase in hospice use in the last 30 days of life, in the SEER-Medicare arm. According to the investigators, these findings indicate that there are opportunities to optimize high-quality EOL care in these settings.

“Our data, drawn from 2 complementary cohorts, illuminate real-world patterns of EOL care and factors associated with these care components during the era of OAAs,” wrote Hannah E. Dzimitrowicz, MD, of Duke Cancer Center, and co-investigators, in the study. “Prior OAA use was associated with increased likelihood of receiving systemic therapy in the last 30 days of life in both cohorts; prior OAA use was also associated with increased likelihood of hospice use in the last 30 days of life.”

Kidney cancer, of which 85% of cases are RCC, was estimated to account for approximately 13,920 deaths in 2022. Although there has been an influx of approved treatments on the market, EOL care is still considered an important component of quality care in this setting.

Studies surrounding EOL care in mRCC have historically been centered around patients receiving traditional intravenous cytotoxic chemotherapy. However, since the approval of sorafenib (Nexavar) in 2005, OAAs have been widely incorporated into clinical use for mRCC, underscoring the need to understand how to optimized EOL practices based on prior use.

Factors which are considered when evaluating the quality of a patient’s EOL care typically involve the following: administration of systemic therapy, hospital admission, intensive care unit (ICU) admission or emergency department (ED) visit within the last 30 days of life, in-hospital death, and hospice initiation. To that end, Dzimitrowicz et al retrospectively analyzed EOL care for those who had died from mRCC and had been registered with the CIPHR following a diagnosis made between 2004 and 2015, or between 2007 and 2015 for the SEER-Medicare.¹

Investigators assessed hospice use in the last 30 days of life, as well as existing measures of poor-quality EOL care, which included hospital admission, ICU admission, and more than 1 ED visit in the last 30 days of life; hospice initiation in the last 3 days of life; and in-hospital death. Multivariable logistics regressions were used to assess the associations between OAA use, patients and provider characteristics and EOL care.¹

Of note, 16% and 14% of patients in the CPHR, and SEER cohorts who received prior OAAs also received these agents in the 30 days before death. Moreover, although the overall number of decedents who had any hospice use in their last 30 days was 48.5% and 42.4% in the 2 groups, the percentage of patients who had prior OAA use, as well as hospice in the 30 days before death was 47.5% vs 40.6% (P = .007).¹

In the SEER-Medicare cohort, hospice initiation in the 3 days prior to death was highest among those who had prior OAA use (13.7% vs 10.3%; P = .042). In the CIPHR cohort, those with previous OAA use were more likely to be admitted to the ICU vs those who did not (19.6% vs 12.0%; P = .037). There were also more likely to have at least 1 ED visit in the 30 days prior to death vs those who did not (16.9% vs 6.8%; P = .002).¹

The percentage of patients who passed away in the hospital was similar (21%) yet in the CIPHR cohort there was a significant difference between those with prior OAA use and those who had not received those treatments (24.7% vs 15.7%; P = .025).¹

This study demonstrated that patients receiving OAAs were likely to remain on therapy during EOL care and were more likely to enroll in hospice care. According to Dzimitrowicz et al, “These data suggest that OAA receipt in clinically declining patients may be a marker of aggressive EOL care, presenting an opportunity to optimize EOL care through interventions such as early palliative care engagement.” They added that better understanding of physician and patient EOL decision making also warrant evaluation in the space.¹

In a companion piece published in the same issue of JCO Oncology Practice, Bergerot et al discussed the findings from this research. Although they noted that the study provides important insight into the current landscape of EOL care for patients with mRCC, they stressed that the study only included the 5 following oral anticancer agents: sunitinib (Sutent), sorafenib, axitinib (Inlyta), everolimus (Afinitor), and pazopanib (Votrient)—although by the time the study was published, in 2023, more oral anticancer agents had been approved for RCC.²

Since the maximum span of the analysis was 2004 to 2015 across databases, Bergerot et al argued that since provisional clinical measures regarding EOL were not introduced until 2012 and palliative care guidelines were not published by ASCO until 2017, these findings could be viewed quite positively, as they suggest clinicians in the United States were not overtreating during EOL despite a lack of consensus guidelines.

Regardless, Bergerot et al agreed that these findings highlight a need for patient-centric decision-making. The authors pointed out that between 10% and 17% of patients will achieve a complete response with new targeted therapy/immunotherapy combinations, and therefore clinicians must balance patient expectations with clear communication around prognosis—particularly as many patients may harbor inaccurate expectations about a cure and that this can effect EOL preferences.

“Clear communication focused on patients’ goals of care should remain a key driver of quality care that includes minimizing unnecessary treatment toward EOL,” they concluded.

References

1. Dzimitrowicz HE, Wilson LE, Jackson BE, et al. End-of-life care for patients with metastatic renal cell carcinoma in the era of oral anticancer therapy. JCO Oncol Pract. 2023;19(2):e213-e227. doi:10.1200/OP.22.00401.
2. Bergerot CD, Liu S, Pal SK. End-of-life care among patients with metastatic renal cell carcinoma: importance of a patient-centric focus in clinical decision making. JCO Oncol Pract. 2023;19(2):70-71. doi:10.1200/OP.22.00732.