This article is more than 5 years old. Information may no longer be current.
Lower-dose chemotherapy benefits older, frail patients with advanced gastroesophageal cancer
Click Here to Manage Email Alerts
A lower-dose, less-toxic regimen of oxaliplatin and capecitabine conferred comparable PFS as the higher-dose regimen among frail and/or elderly patients with advanced gastroesophageal cancer, according to results from the randomized phase 3 GO2 trial scheduled for presentation at ASCO Annual Meeting.
Results also showed the lower-dose chemotherapy regimen appeared associated with superior quality of life.
“Gastric and esophageal cancers are diseases of the elderly — in the U.K., the average age at diagnosis of advanced gastroesophageal cancer is around 75 years, and many of these patients demonstrate frailty or suffer medical comorbidity,” Peter S. Hall, PhD, clinical senior lecturer on cancer informatics and health economics at University of Edinburgh, said during a press cast. “Standard chemotherapy has been developed over a number of historical clinical trials, which predominantly included younger patients, average age 65 [years], who are predominantly free of medical comorbidity or demonstrable frailty. Chemotherapy in this situation has consisted of a three-drug regimen.”
However, as most patients diagnosed with esophageal cancer — including more than 17,000 in the U.S. each year — are elderly or frail, the majority cannot tolerate the standard combination of three chemotherapy drugs.
In the randomized, phase 3 GO2 trial, Hall and colleagues sought to determine the optimal dose of a two-drug combination — capecitabine and oxaliplatin, also referred to as XELOX — among 514 patients with advanced gastroesophageal cancer enrolled at 61 U.K. centers between 2014 and 2017. Eligibility criteria included suitability for reduced-intensity chemotherapy but not for full dose epirubicin/oxaliplatin/capecitabine, glomerular filtration rates of 30 or higher, and bilirubin less than two times the upper limit of normal.
Researchers assessed patients’ quality of life, symptoms, functional scores, comorbidity and frailty at baseline. They randomly assigned patients 1:1:1 to one of three dose levels:
- level A: 130 mg/m² oxaliplatin on day 1 and 625 mg/m² capecitabine twice daily on days 1 to 21 of a 3-week cycle (n = 170; median age, 76 years; 61% very frail);
- level B: 80% of level A doses (n = 171; median age, 76 years; 56% very frail); or
- level C: 60% of level A doses (n = 173; median age, 77 years; 58% very frail).
Patients with compromised kidney function received 75% of the capecitabine doses.
Evaluation of overall treatment utility — which included factors such as clinical benefit, tolerability, patient satisfaction and quality of life — occurred at week 9 week, at which point therapy continued at the clinicians’ discretion.
The researchers evaluated noninferiority of the lower doses vs. level A using PFS censored at 12 months, with a boundary HR of 1.34, based on conversations with clinicians and patients, and 284 PFS events needed for two-way comparison. The researchers analyzed baseline fitness as a predictor of overall treatment utility, both overall and by interaction with dose.
Results showed noninferiority of PFS for level B vs. level A (HR = 1.09; 95% CI, 0.89-1.32), and for level C vs. level A (HR = 1.1; 95% CI, 0.9-1.33).
Fewer toxicities occurred among patients who received the level C dose, as well as better overall treatment utility scores (43%) than patients who received level A (35%) or level B (36%) doses.
Survival outcomes among level A, level B and level C showed similar median OS (7.5 months vs. 6.7 months vs. 7.6 months) and PFS (4.9 months vs. 4.1 months vs. 4.3 months).
Grade 3 or higher nonhematologic adverse events occurred among 56% of patients in the level A and B groups, compared with 37% of patients in the level C group.
Analysis based on age at baseline, frailty and patient satisfaction showed level C had the best overall treatment utility among younger and less frail patients. The higher dose levels did not result in greater benefit for any group.
“This is the largest randomized clinical trial to date specifically investigating frail and/or elderly [patients with] advanced gastroesophageal cancer, and the lowest dose tested as noninferior in terms of PFS and produced less toxicity,” Hall said. “Low-dose treatment may be offered to patients who are suitable for chemotherapy but considered 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.” – by Jennifer Byrne
Reference:
Hall PS, et al. Abstract 4006 Scheduled for presentation at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Disclosures: Hall reports consultant/advisory roles with Elsai, Pfizer and Roche, and research funding to his institution from AstraZeneca, Daiichi Sankyo, Novartis and Roche. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
Back to Top
Nicholas C. Rohs, MD
This is the kind of data that oncologists love to see. One common assumption is that oncologists like to give more and more chemotherapy, but we actually like to give less, and if we can get a more tolerable regimen with equivalent outcomes, that is fantastic.
In a highly deadly disease that is lacking a lot of data because of its rarity, it is great to see new data that can support what we’re doing in clinic. XELOX is a very common regimen we use in our clinic, and to be able to reduce the dose, which I do in my own practice empirically, is very exciting. There still is a subset of patients that I have been concerned about treating, and this may open up the option of treatment for those patients and give them more quality time with us. That is the balance we are trying to strike in clinic. This may also open the option of second-line therapies for patients who do well on the first line and have a fair performance status. We may be able to offer them single agents, or possibly immunotherapies, in the second line.
I’d love to see a little bit more data on how these results might apply to younger, less frail patients. Even when I put my healthy patients through a regimen like XELOX, they can get fairly beaten up.
Also, the investigators use an interesting quality-of-life metric — overall treatment utility — that has been used in two other studies. It would be great to further validate that endpoint, because many of our studies are incorporating these quality-of-life metrics.
Read more about
Click Here to Manage Email Alerts