Future Analyses From the 80405 mCRC Trial

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The phase III CALGB/SWOG 80405 trial enrolled 1137 patients with KRAS wild-type metastatic colorectal cancer (mCRC) over the course of 10 years, representing a vast amount of data for future analyses. Topline results from the study revealed that overall survival (OS) was similar in patients with mCRC treated with chemotherapy plus either upfront bevacizumab or cetuximab. The median OS was 29 months with bevacizumab and 29.9 months with cetuximab. The median progression-free survival (PFS) with bevacizumab was 10.8 versus 10.4 months with cetuximab.

In addition to expanded RAS testing, broad molecular analysis will be conducted looking at several alterations, notes Alan P. Venook, MD. Moreover, once all data points are collected, an information technology group will further analyze the results in order to discover subtypes and potential biomarkers. Additionally, this analysis will look at the 10% of patients in the study who went on to receive potentially curative surgery.

Subsequent therapies and the impact of receiving either bevacizumab or cetuximab on second-line therapy is another aspect that needs explored, suggests Al B. Benson III, MD. This will help establish a consistent continuum of care, since OS was significantly longer than traditional benchmarks while PFS remained somewhat consistent, believes Axel Grothey, MD.

In general, the goal of treatment is to administer as little therapy as possible while producing the best outcomes with minimal toxicity, notes Grothey. In many cases, maintenance therapy helps achieve this goal for some patients. In the CAIRO3 trial, maintenance therapy with capecitabine plus bevacizumab was compared with observation for patients who responded to induction treatment with capecitabine, oxaliplatin, and bevacizumab. Overall, a significant correlation between OS and treatment was demonstrated in a multivariable analysis.

Maintenance therapy and breaks remain important, since it is not practical to keep patients on treatment for 29 months, states Venook. Treatment holidays and short breaks should be utilized to control toxicity. However, when giving these breaks, it is important to remain mindful that long pauses in treatment may result in full discontinuation, suggests Charles D. Blanke, MD. To address this concern in the 80405 trial, if a treatment break was longer than 28 days the patient was removed from the trial. Short breaks lasting a few weeks can be utilized to control toxicity but longer pauses consisting of a few months can negatively impact overall outcomes, Venook states.

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