A phase III study comparing doses of oxaliplatin plus capecitabine in elderly or frail adults with advanced gastroesophageal cancer found that the lowest examined dosage was non-inferior to the highest dosage in terms of delaying progression and minimizing side effects.
The study (abstract 4006) was presented by Peter S. Hall, PhD, of the University of Edinburgh, at a presscast ahead of the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, which will be held May 31–June 4 in Chicago.
“Low-dose treatment may be offered to patients who are suitable for chemotherapy but too frail or elderly for a full-dose standard regimen, in the confidence that it can produce superior outcomes without compromising cancer control or survival,” Hall said.
The average age of patients diagnosed with gastroesophageal cancer in the United Kingdom is 75 years, and many are frail, Hall noted. Standard chemotherapy for this condition was developed in trials in which patients were an average of 65 years, and predominantly non-frail. After auditing UK oncologists, Hall and colleagues found that most used reduced chemotherapy schedules to treat their frail or elderly patients with gastroesophageal cancer, but without evidence to guide them.
In a prior phase II study, Hall and colleagues compared three regimens in older patients with advanced gastroesophageal cancer—epirubicin, oxaliplatin, and capecitabine vs oxaliplatin and capecitabine vs capecitabine alone—and found that oxaliplatin plus capecitabine yielded the best results.
This phase III study included 514 patients age 51 to 96 years who were ineligible for full-dose epirubicin, oxaliplatin, and capecitabine because of age or frailty, but who were fit for oxaliplatin plus capecitabine. The patients were randomly assigned 1:1:1 to one of three doses: level A, oxaliplatin 130 mg/m2 once every 21 days plus capecitabine 625 mg/m2 twice a day; level B, 80% of level A dosage; and level C, 60% of level A dosage.
After 9 weeks, patients were scored using a tool called Overall Treatment Utility (OTU), a composite of clinical benefit, tolerability, quality of life, and patient value.
Patients assigned to the lowest dosage, level C, had fewer toxic effects and better OTU outcomes than those assigned to level A or level B. Level C produced the best OTU outcomes, even in younger patients and those who were less frail. No group benefited more from a higher dosage.
Survival outcomes were assessed as secondary measures. Overall and progression-free survival were similar across the three study arms. Median overall survival was 7.5 months for level A, 6.7 months for level B, and 7.6 months for level C. Median progression-free survival was 4.9 months for level A, 4.1 months for level B, and 4.3 months for level C.
Although more than half of patients assigned to level A and level B experienced grade 3 or worse adverse events, this occurred in only 37% of patients assigned to level C.
“One of the things that all oncologists who treat adults struggle with are a lack of data on elderly patients,” said ASCO President Monica M. Bertagnolli, MD, FACS, FASCO. “Sixty percent of the patients we treat are elderly, but unfortunately only 10% of our clinical trials data come from patients who are elderly.”
She praised Hall and colleagues for their dedication to the “very special, but certainly far from uncommon” patient population.