NEW YORK (Reuters Health) – Androgen receptor inhibitors improved survival in men ages 80 and older with non-metastatic, castration-resistant prostate cancer in a pooled analysis by the US Food and Drug Administration.
“Older adults remain dismally underrepresented in most cancer clinical trials, due to a variety of factors, including restrictive eligibility criteria,” Dr. Jaleh Fallah of the FDA’s Center for Drug Evaluation and Research told Reuters Health by email. “There is biologic rationale to include older adults in all stages of cancer drug development, given the physiologic changes that naturally occur with aging.”
“Treatment decisions should be based on the patient’s overall clinical condition and not merely on the patient’s age,” she said. “Use of geriatric assessment tools can be helpful in assessing the potential risk of treatment-related adverse events and to implement appropriate risk-mitigation strategies to prevent such events as possible.”
As reported in The Lancet Oncology, Dr. Fallah and colleagues searched the literature through August 2020 and identified three randomized controlled trials that met the selection criteria. All patients had an Eastern Cooperative Oncology Group performance status of 0-1, castration-resistant prostate cancer, prostate-specific antigen 2.0 mcg/L or greater, PSA doubling time of 10 months or less, and no evidence of distant metastatic disease.
Younger patients in the intervention and placebo groups had a median age of 71 and 74% were white; older patients had a median age of 83 and 69% were white. The effects of age on metastasis-free and overall survival were assessed in the intention-to-treat population. Safety analyses were done in patients who received at least one dose of study treatment.
Between 2013 – 2018, across the three trials, 2,694 patients were assigned to an androgen receptor inhibitor (apalutamide, enzalutamide, or daralutamide) and 1,423 to placebo.
In older patients, the estimated median metastasis-free survival was 40 months in the androgen receptor inhibitor groups and 22 months in the placebo groups (adjusted hazard ratio, 0.37); median overall survival was 54 months versus 49 months, respectively (adjusted HR, 0.79).
In younger patients, the estimated median metastasis-free survival was 41 months in the androgen receptor inhibitor groups and 16 months in the placebo groups (adjusted HR, 0.31); median overall survival was 74 months versus 61 months (adjusted HR, 0.69).
Grade 3 or worse adverse events were reported in 55% of older patients in the intervention group and 41% of those on placebo.
In younger patients, 44% in the androgen receptor inhibitor groups and 30% of those on placebo experienced grade 3 or worse adverse events.
The most common grade 3-4 adverse events were hypertension (8% of both older and younger patients on androgen receptor inhibitors vs. 6% of older placebo patients and 5% of younger) and fracture (5% of older patients on androgen receptor inhibitors vs. 3% on placebo, and 3% vs. 1%, respectively, of those on placebo).
Dr. Ali Zhumkhawala, a urologic oncology surgeon at City of Hope in Duarte, California, called the findings “clinically helpful,” noting, “the caveat is that patients who received the second-generation androgen receptor inhibitors did show higher rates of severe adverse events. While the quality-of-life questionnaire did not show a downside to treatment with these medications, the higher risk of side effects needs to be taken into account and treatment should be personalized per patient.”
“I would like to see this study, or a similar study, stratify these outcomes based on the specific medication used,” he said. “There are concerns about the use of enzalutamide in the elderly. I would like to see the adverse events, survival and questionnaire data broken down by which medication the patient received so that we can further assess which specific medicine works best in which age group.”
“My take-home message is that clinicians should strongly consider the use of second-generation androgen receptor inhibitors in patients with castrate-resistant prostate cancer that has not metastasized. This seems to hold true in both younger and elderly patients,” Dr. Zhumkhawala concluded.
Dr. Fallah noted, “The FDA encourages broader inclusion of older adults in cancer clinical trials and has issued a guidance for industry providing advice on the inclusion of older patients in early-phase and pivotal clinical trials, as well as in the post-market setting. Additionally, the FDA includes information on the use of drugs in older patients on drug labels,” as applicable.
SOURCE: https://bit.ly/3AgP8U4 The Lancet Oncology, online July 23, 2021.
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