Deferred systemic therapy may be common in patients with metastatic renal cell cancer

By Liz Meszaros, MDLinx
Published December 1, 2017

Key Takeaways

In patients with metastatic renal cell cancer (mRCC), deferred systemic therapy (DST) seems to be a common choice among clinicians in both academic and community care settings. These patients usually have both a better risk profile and better functional status compared with patients treated with systemic therapy (ST), according to preliminary study results presented at the Sixteenth International Kidney Cancer Symposium, in Miami, FL.

“We had 184 patients in whom systemic therapy was deferred. We saw that those patients did pretty well in terms of the deaths in that cohort versus the overall cohort. There is a relatively high percentage of patients who are still in DST at 2, 3, 5 and even 10 years after diagnosis with metastatic disease,” said lead author Michael R. Harrison, MD, assistant professor of medicine, Duke Cancer Institute, Durham, NC.

Dr. Harrison and colleagues created the MarCC registry as a prospective, observational, phase 4 study to identify baseline characteristics, demographics, and reasons for clinicians' decisions for patients in whom their initial management decision was to defer systemic therapy.

They included 501 patients (median age: 65 years) from 46 academic and community sites in the US, from March 24, 2014, to December 22, 2016. The study is scheduled to continue from approximately 5 years. Dr. Harrison presented preliminary results at the symposium.

Of the total population, 184 patients were given DST while 317 received systemic treatment (ST). In all, 72% of DST patients were male vs 69% ST patients, and comprised 70% of the total population. In addition, 90% of DT patients were white, compared with 81% in the ST population, and comprised 85% of the total patients.

Of the 42% of patients who were Eastern Cooperative Oncology Group performance status (ECOG PS) 0 at baseline, 48% were DST vs 39% ST. As ECOG PS grade increased, the number of patients decreased, with only 9% being ECOG PS 2 and 2% ECOG PS 3. Fourteen percent of patients did not have ECOG PS available. In all, 78% of patients had clear cell histology, 80% DST vs 77% ST.

Prior nephrectomy had been performed in 55% of all patients (57% DST vs 54% ST).

Finally, Dr. Harrison and colleagues found that when patients were evaluated for Heng risk factors, most were ranked as a 0 (favorable) (29%), with significant differences between the DST and ST patients (53% vs 15%, respectively). Furthermore, 57% of all patients were ranked at intermediate risk (Heng 1-2), with more ST patients in this category compared with DST (64% vs 47%, respectively).

When assessed with the National Comprehensive Cancer Network/ Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index 19 (NCCN-FACT FKSI-19), DST patients had better patient reported outcomes compared with those ST patients in physical well-being (P=0.0011), social well-being (P=0.9675), emotional outcomes (P=0.002), and functional well-being (P=0.0009)

“Patients in whom systemic therapy was deferred had a better risk profile, they had a better performance status, they had better characteristics such as the IMDC risk factors, time from diagnosis to treatment for metastatic disease,” said Dr. Harrison. “They also, interestingly, had better patient reported outcomes. So, whether you looked at Functional Assessment of Cancer Therapy, general (FACT-G) or FACT-Kidney Symptom Index-19 (FKSI-19) as well as most of the subscales of the FACT-6, these were better, and clinically significantly so, in the DST cohort versus the systemic therapy cohort,” he added.

The mortality rate was 25%, with significantly more patients in the ST group dying compared with those in the DST group (34% vs 9%, respectively).

In all, 63% of patients were managed with active surveillance (64% of patients in academic settings, and 60% of those in community settings. Of these, 40% had disease present (44% vs 23%, respectively), 22% had no evidence of disease following a procedure (19% vs 37%), and 1% not otherwise specified (1% vs 0%).

In 17% of patients, the primary reasons for DFS was local therapy, and in 2%, poor prognosis. Finally, in 18% of patients, the primary reasons for DFS were comprised of “other” reasons, including patient declining treatment (7%), waiting for systemic therapy (5%), waiting for management decision to be made (5%), and disease progression (1%).

This is, to-date, the largest prospective experience of DST in mRCC patients (n=184), and suggests that DST is common. After a mean follow-up of 10.5 months, 25% of treatment-naïve mRCC patients remain on DST.

“DST patients represent a sizeable cohort of patients that have been underrepresented. This is the first data to really have a denominator. We can now say that DST is common in academic practice, it’s common in community practice, it’s common across a wide range of risk factors and demographic factors as well. So we need to think about how to optimally treat those patients and perhaps design clinical trials to account for this group that has really been under-recognized,” concluded Dr. Harrison.

This study was sponsored by Pfizer.

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