Expert Point of View: Axel Grothey, MD

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Axel Grothey, MD

These studies inform our clinical practice and have a meaningful impact on how we treat our patients.

—Axel Grothey, MD

Putting the maintenance trials into context was Axel Grothey, MD, Professor of Oncology at the Mayo Clinic, Rochester, Minnesota, who commented, “These studies inform our clinical practice and have a meaningful impact on how we treat our patients.”


In the DREAM Trial, Dr. Grothey questioned the use of bevacizumab (Avastin) alone as the control arm as well as the heterogeneity of the induction regimens, but said “the results validate the trial design and make the study interesting.”

Bevacizumab/erlotinib yielded a 23% reduction in progression, despite a very short duration of erlotinib treatment (median, 3.6 months), and the hazard ratio (HR) was similar for overall survival (HR = 0.79). “The study is remarkable in retaining the differences between the arms,” he said, though he cautioned that “the curves separate late and the delta is based on very few patients.”

The similarity in postprogression therapy suggests that this difference was driven by the short duration of therapy with erlotinib, a drug that has not shown efficacy as a single agent in colorectal cancer. Interestingly, no impact from KRAS status was observed, Dr. Grothey pointed out.

He noted that the bevacizumab/erlotinib doublet is also showing interesting activity in other tumors. In non–small cell lung cancer, this regimen has reduced progression by 29% to 46% in recent studies. He concluded that the results of DREAM are “a bit puzzling” and warrant confirmatory studies.

AIO KRK 0207

The AIO trial contained an interesting three-arm design, but the noninferiority assumption was “too generous,” according to Dr. Grothey. “I am not a fan of looking for noninferiority. We are trying to get better outcomes for patients, and we should not be asking how much lower we should set the bar,” he commented.

He felt the 24-week induction regimen was too long and suggested that the low rate of reinduction in the combination arm (21%) affected the primary endpoint.

Nevertheless, the findings mirror the guidelines and clinical practice, and further studies are not needed, he concluded. “We are validating that something for maintenance is better than nothing, and fluoropyrimidine/bevacizumab is the winner here. For future maintenance studies, this regimen is the appropriate control arm.”


The evaluation of the EGFR monoclonal antibody as maintenance therapy is interesting, and the findings are hypothesis-generating, said Dr. Grothey, who felt the results were “as expected” and that additional studies are warranted.

“The results do not yet have implications for clinical practice, and this is clearly not a standard of care. One could question whether EGFR monoclonal antibodies are the right agents for long-term treatment,” he said. “We need to refine the population that can benefit.” ■

Disclosure: The Mayo Foundation has received funding from Genentech, Bayer, Pfizer, Eisai, and Eli Lilly for research conducted under Dr. Grothey’s leadership.


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