Chicago, IL—Reduced-dose chemotherapy is as effective as full-dose chemotherapy for frail elderly patients with advanced gastroesophageal cancer, according to results of the phase 3 GO2 clinical trial presented at ASCO 2019. Lower doses of oxaliplatin plus capecitabine (OCap) led to similar survival outcomes and improved quality of life compared with higher doses of that regimen.
“GO2 is the largest randomized controlled trial to date specifically investigating frail and/or elderly advanced gastroesophageal cancer patients, and results should guide future treatment. The lowest dose tested was noninferior in terms of progression-free survival and produced less toxicity and better overall treatment utility,” said lead investigator Peter S. Hall, MBChB, MRCP, PhD, Medical Oncologist, University of Edinburgh, Scotland.
Study Findings and Rationale
The median progression-free survival was 4.9 months with the highest OCap dose, 4.1 months with intermediate doses, and 4.3 months with the lowest dose. The median overall survival was 7.5 months at the highest dose level, 6.7 months at the intermediate dose level, and 7.6 months at the lowest dose level.
The GO2 clinical trial used the overall treatment utility, a composite measurement tool, to assess the therapeutic value of a treatment regimen. Overall treatment utility incorporates conventional treatment response assessment, along with tolerability and quality of life. According to the overall treatment utility score, the reduced-dose regimen provided the best outcomes. At week 9, good overall treatment utility was reported in 35% of patients who received treatment at the highest dose of OCap, 36% of those who received treatment at the intermediate dose, and 43% of those who received treatment at the lowest dose. Poor overall utility was reported in 31%, 38%, and 29% of patients, respectively.
“The overall treatment utility tool could represent a new paradigm for how to assess outcomes in older patients with late-stage disease,” Dr Hall said.
Advanced gastroesophageal cancer is typically a disease of the elderly. These patients often have comorbidities and are frail, and they may not be able to tolerate full-dose chemotherapy.
Practice patterns vary widely in the United Kingdom, so Dr Hall and colleagues conducted a feasibility study to identify an appropriate regimen for this group of patients. They found that OCap was superior to a 3-drug regimen that included epirubicin plus OCap.
The study included 514 frail or elderly patients with advanced gastroesophageal cancer who were unfit for full-dose chemotherapy. The patients were randomized in a 1:1:1 ratio to one of 3 dose levels—level A (oxaliplatin 130 mg/m2 on day 1, every 21 days, and capecitabine 625 mg/m2 twice daily on days 1-21); level B (80% of level A doses); or level C (60% of level A doses). After 9 weeks, the patients were scored using the overall treatment utility tool. Treatment continuation was based on clinician judgment.
Grade 3 or 4 adverse events were reported in 56% of patients who received treatment at level A and level B doses compared with only 37% of patients who received treatment at the lowest dose.
“We hope that our finding helps patients make an informed choice between low-dose chemotherapy and no chemotherapy at all, with the knowledge that low-dose chemotherapy can prove beneficial and still allow them to maintain some quality of life,” Dr Hall stated.
ASCO President Weighs In
“Oncologists struggle with a lack of data on elderly frail patients, which represent about 60% of the patients we treat. Only 10% are included in clinical trials. It is wonderful to have real data that will help guide their treatment,” commented ASCO President Monica M. Bertagnolli, MD, FACS, FASCO, Chief, Division of Surgical Oncology, Brigham and Women’s Hospital.
“‘Less is more’ is becoming a common refrain in some areas of cancer treatment, and one that is paying off for patients’ quality of life. This trial seeks to balance quality of life and increased survival for older and frail people receiving palliative treatment for gastroesophageal cancer, providing data that we sorely need for this patient population. These data are important, because they provide a potential new option for patients to slow the progression of disease,” Dr Bertagnolli added.