The lowest dose of oxaliplatin/capecitabine tested was as effective in elderly and frail patients with advanced gastroesophageal carcinoma as the highest dose investigated. It was also associated with fewer side effects and a better quality of life.
The results of the prospective randomized open-label phase III study GO2 with 512 patients were presented by Peter S. Hall, University of Edinburgh, UK, at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 2, 2019.
"In median, patients are 75 years old at the time of diagnosis of advanced, inoperable gastroesophageal carcinoma, and many are frail," says Hall. "However, the standard chemotherapy regimens are being developed with the help of clinical trials in which mostly non-frail patients under the age of 65 were enrolled."
A survey conducted by Hall in 2011 among British oncologists showed that most elderly and frail patients reduced the dose of chemotherapy, although there is virtually no evidence of this. In a randomized phase II study (321GO), the British working group compared different chemotherapy regimens in frail elderly patients with gastroesophageal carcinoma with oxaliplatin and capecitabine being the best acting substances.
Therefore, Hall and his colleagues now investigated the benefits and risks of different doses of oxaliplatin and capecitabine chemotherapy in elderly patients with gastroesophageal carcinoma in a randomized, multicenter, prospective open phase III GO2 study. The study was designed for non-inferiority. Between 2014 and 2017, 61 centers in Great Britain included 512 patients at the median age of 76 years who were not sufficiently fit for chemotherapy with three substances but were eligible for chemotherapy with reduced intensity. Randomized, they were treated as follows:
On the one hand, the non-inferiority of the lower doses compared to arm A in the effect on progression-free survival (PFS) should be demonstrated. Secondly, the dosage of the best Overall Treatment Utility (OTU) was determined, which included disease control, side effects, quality of life and patient assessment.
The results of the study clearly show that the lowest dose of oxaliplatin/capecitabine was not inferior to the higher doses in terms of progression-free and overall survival (arm B vs. A hazard ratio 1.09, arm C vs. A HR 1.10). Overall survival in all three groups was comparable with 7.5 months (arm A), 6.7 months (B) and 7.6 months (C). Progression-free survival was also similar to 4.9 months (A), 4.1 months (B) and 4.3 months (C).
In addition, Arm C achieved the highest OTU score with 43%, which was due to better tolerability of the therapy and a better quality of life of the patients. In arms A and B, the score was 35 and 36% respectively. In arms B and C, the quality of life improved on average compared to the initial value.
The tolerability of the therapy was best in Arm C, where patients could also be treated more with one therapy cycle.
"This is the largest randomized trial in this age group to date," said discussant Ian Chau, Royal Marsden NHS Foundation Trust, UK. Clinical trials would usually be conducted on younger patients. Although in studies comparing younger and older patients both achieved similar PFS or OS, patients should be sufficiently fit for therapy.
The study had fulfilled the primary endpoint, as the PFS the non-inferiority had been proven. None of the doses examined had been found to be better. Normally, an HR equivalence limit of 1.2 was set in non-inferiority studies, but in GO2 it was set at 1.34 in the PFS, which Chau described as "generous". He described the consequences as follows: "For the GO2 study, a predefined non-inferiority limit for HR of 1.34 with a PFS duration of 4.4 months in the control arm means that we accept a PFS of about 3.2 months as not inferior in the group with reduced CAPOX dose." The GO2 study is a study with a PFS duration of 4.4 months in the control arm. Nevertheless, it was clear to him that elderly and frail patients could be treated with a reduced dose. However, more and more patients would also receive second- and third-line therapy, which is why it would now be necessary to investigate further how these therapies are designed in order to prolong the OS.
Hall PS, et al. Optimizing chemotherapy for frail and elderly patients (pts) with advanced gastroesophageal cancer (aGOAC): The GO2 phase III trial ASCO 2019, Chicago, May 31 to June 4, 2019, Abstract 4006, http://abstracts.asco.org/239/AbstView_239_259067.html