The treatment of elderly patients with mCRC is still considered to be a debatable issue. Despite the fact that the majority of patients are diagnosed in advanced age, elderly patients under-represented in randomized clinical trials. In addition, the vast majority of elderly patients included in randomized trials are usually selected and only fit elderly patients are finally enrolled. Due to this fact, no definitive conclusion can be drawn regarding the treatment of this population group with mCRC.
The current study describes the results of a chemotherapy doublet plus bevacizumab in elderly patients selected upon CGA. Our results show that the triple combination of XELOX/BEV is effective and well tolerated among fit and vulnerable elderly patients with mCRC. The response rate, PFS and OS compares well to results in younger populations reported in the literature.
Our study has several strengths. First of all, to our knowledge this is the first study to prospectively assess a three drugs combination specifically in an elderly-only population. Designing geriatric-specific chemotherapy trials has been shown to allow for the prediction of treatment related toxicities . This is further supported by our study where the rates of reported adverse events were very low. Also, compliance was excellent with very low rates of dose reduction or cycle postponement. Other strengths of our study include the systematic use of comprehensive geriatric assessments and the homogenous study population, which allowed for careful dose tailoring which led to high response rates with minimal toxicity.
On the other hand, our study suffers from several weaknesses. It is a phase II study with a small number of patients. As a result, we were unable to identify predictive and prognostic factors derived from the Comprehensive Geriatric Assessments. Also, our study population was limited only to fit and vulnerable elderly patients, so our results may not be representative in frail patients with mCRC.
Previous studies have established the efficacy and safety of combination chemotherapy in elderly patients [8–11]. The addition of bevacizumab to chemotherapy in geriatric populations has also been shown to be effective in observational cohort studies, subgroup analyses and pooled analyses of cohorts of other randomized trials [20–23]. Recently, the results of the first randomized Phase III study of capecitabine plus bevacizumab exclusively in elderly patients were published (AVEX trial: bevacizumab plus capecitabine versus capecitabine in elderly patients with previously untreated metastatic colorectal cancer) . Taking into account the inherent hazards of cross-study comparisons, OS was similar between the AVEX trial and our study. However, response rates were higher with the triple drug combination and adverse events were lower. In addition, the patient population in the AVEX study was quite different since it was based on clinical judgment that the patient was not suitable for oxaliplatin or irinotecan-based doublets. It seems that the next logical step would be to directly compare these two regimens; until such data are available, modified XELOX/BEV might be an alternative option for patients requiring a relatively rapid and objective clinical response, such as in patients with potentially resectable disease or in those with rapidly progressive disease and/or with a need for symptoms relief.