CHICAGO — A reduced-dose palliative regimen for older and mostly frail patients with advanced gastroesophageal cancer yielded similar survival to a standard regimen, but with lower rates of high-grade toxicity and better quality of life, a randomized trial found.
Among this group of patients — more than half of whom were considered very frail — the lowest dose of oxaliplatin and capecitabine (Xeloda) was found to be non-inferior to standard treatment for the primary endpoint of progression-free survival (HR 1.10, CI 0.90-1.33) and produced less toxicity, reported Peter S. Hall, PhD, of the University of Edinburgh in Scotland.
“Low-dose treatments may be offered to patients who are suitable for chemotherapy, but considered either too frail or too elderly for a full-dose standard regime, in the confidence that it can produce superior outcomes without compromising cancer control or survival,” he said during a press briefing ahead of the American Society of Clinical Oncology (ASCO) meeting, which begins here May 31.
From 2014 to 2017, the phase III GO2 trial randomized 514 patients in the United Kingdom with advanced gastric or esophageal cancers to one of three treatment arms:
- 130 mg/m2 oxaliplatin every 21 days plus 625 mg/m2 capecitabine twice daily (Level A)
- Level A regimen but at 80% the dosage (Level B)
- Level A regimen but at 60% the dosage (Level C)
Compared with the full-dose regimen, progression-free survival was found to be non-inferior in the two reduced-dose groups: 4.9 months (Level A) versus 4.1 months (Level B) and 4.3 months (Level C). Overall survival was comparable between the three groups: 7.5 months versus 6.7 and 7.6 months, respectively. Rates of grade 3 or higher toxicity occurred in 56% of the Level A and B groups and in 36% of the Level C group.
“One of the things that all oncologists who treat adults struggle with is a lack of data on elderly patients — 60% of the patients we treat are elderly, but unfortunately only 10% of our clinical trials data comes from patients who are elderly,” said ASCO President Monica M. Bertagnolli, MD, during the briefing. “It is wonderful to have real data to help guide their treatment.”
The researchers also examined the secondary endpoint of overall treatment utility at 9 weeks, which takes into account six different domains: cancer progression, severe toxicity, global quality of life, oncologist’s assessment of clinical benefit, as well as a patient score that the treatment was worthwhile and not interfering with daily activities.
“Patients on dose Level C had a better overall treatment utility compared to patients either on Level A or Level B, and this was due to lower side effects and better quality of life in those patients presumably,” said Hall.
In the lowest-dose group, 43% of patients had good overall treatment utility compared with 35% in the full-dose group. While 29% and 31%, respectively, had poor overall treatment utility at week 9.
“This is the kind of data that oncologists get excited about — being able to give more tolerable treatments with comparable outcomes,” Nicholas Rohs, MD, of Tisch Cancer Institute at Mount Sinai in New York City, who was not involved with the research, told MedPage Today in an email. “To know that we can reduce doses, without sacrificing benefit, will allow me to give this therapy to more patients than before.” Rohs added that the combination regimen is commonly used in his clinic.
A previous trial in a similar population found the three-drug combination of oxaliplatin, capecitabine, and epirubicin (Ellence) to be too toxic. The current study aimed to further improve the palliative treatment tolerability for these patients.
Median patient age in GO2 was 76 years (range 51 to 96). Those with decreased kidney function received 75% of the capecitabine doses. Roughly one-third (31%) of patients in each arm had an ECOG performance status ≥2. Most patients were considered frail (86%, 82%, and 76% in Levels A, B, and C, respectively) with a majority considered very frail (61%, 56%, 58%, respectively). Eligibility criteria included those fit enough for chemotherapy, but unfit for the three-drug regimen.
Hall noted that this is the largest randomized controlled trial to date specifically investigating frail or elderly patients with advanced gastric and esophageal cancers.
Hall reported relationships with Roche, Pfizer, Eisai, Novartis, AstraZeneca, and Daiichi Sankyo.