Age May Not Impact Outcomes from Metastatic Renal Cell Carcinoma Treatment Despite Increased Toxicity in Older Patients

CURE, Winter 2021,

Patients older than 75 years experienced more toxicity with mTOR inhibitors, tyrosine kinase inhibitors and checkpoint immunotherapy compared with those younger than 75 years, but researchers found that age did not impact outcomes like progression-free survival and overall survival.

Older patients — specifically those at least 65 years of age — with metastatic renal cell carcinoma were more likely to have toxicity when treated with first-line tyrosine kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors or checkpoint immunotherapy compared with younger patients, although this increased toxicity did not impact outcomes in these older patients.

These agents, in one way or another, can block the action of certain enzymes and protein kinases that perform several cell functions such as growth, signaling and division, thus potentially halting the growth of cancer cells.

“Proactive dose modification/interruption, and patient and physician awareness may help to reduce toxicity while maintaining efficacy,” the study authors wrote in the paper published in the Journal of Geriatric Oncology.

Researchers analyzed data from 838 patients with metastatic renal cell carcinoma who were treated with first-line tyrosine kinase inhibitors (87%), mTOR inhibitors (5%) or checkpoint immunotherapy (8%). Patients were analyzed in subgroups by age: younger than 65 years (42%), 65 to 74 years (39%) and 75 years or older (19%). End points assessed in this study include progression-free survival (PFS), defined as the time from the start of therapy to disease progression or all-cause death; overall survival (OS), defined as the time from the start of therapy to all-cause death; and time to treatment discontinuation, defined as the time from the start of therapy to discontinuation for any reason including disease progression, toxicity, death or another cause.

Patients 75 years and older took lower toxicity-adjusted doses of the tyrosine kinase inhibitor Votrient (pazopanib; 300 mg) compared with those ages 65 to 74 years (400 mg) and patients younger than 65 years (600 mg). This was also seen with another tyrosine kinase inhibitor Sutent (sunitinib; 25 mg, 37.5 mg and 50 mg, respectively).

Patients older than 75 years received two doses of checkpoint immunotherapy, whereas younger patients received more doses, as both groups received five doses each.

Dose reductions or interruptions occurred in 76% of patients aged 75 years and older, in 55% of those aged 65 to 74 years and in 41% of patients younger than 65 years. Older patients also had a shorter mean time to dose reduction or interruption at 0.5 months compared with patients aged 65 to 74 years (1.9 months) and those younger than 65 years (3.4 months).

After adjusting data for prognostic risk scores and the microscopic anatomy of the disease, the findings determined that age did not impact PFS, OS and time to treatment discontinuation.

“Data most inevitable indicates that older patients ought not to be restricted in their access to both therapeutic options and several treatments in succession,” the study authors wrote. “Present data reveals the message that (adverse events) and the consequences hereof were not necessarily unfavorable. Treatment efficacy depends on the proactive toxicity-adjusted dosage of drugs.”

The study authors elaborated on several factors to consider when making treatment decisions. They wrote, “Each patient’s point of view must be taken into account not only managing short-term goals, but also long-term goals, concerns, expectations and needs. On the same note, decisions about cancer treatment should not only take age into account, but crucially their disease-related condition, resulting in individualized patient-centered interventions.”

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