Extra Commentary
Will the results of the Phase III FIRE-3 study comparing first-line FOLFIRI/bevacizumab to FOLFIRI/cetuximab in patients with KRAS WT mCRC change your practice (Heinemann V et al. Proc ASCO 2013;Abstract LBA3506)?
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Steven R Alberts, MD, MPH |
| Chair, Division of Medical Oncology Professor of Oncology Mayo Clinic Rochester, Minnesota |
At this point, the results of the FIRE-3 study have not altered my practice. The study showed differences between the 2 arms in terms of overall survival. However, this could have been because of differences in later-line therapy. Until we have additional data clarifying what types of therapy patients received in later lines and how the patients fared overall, I’m reluctant to change my practice.
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Al B Benson III, MD |
| Professor of Medicine Associate Director for Clinical Investigations Robert H Lurie Comprehensive Cancer Center of Northwestern University Chicago, Illinois |
The study results showed no difference in progression-free survival or response rate between the 2 regimens. The overall survival curves showed a separation, but it was not until much later in the follow-up period. So it’s a stretch to think that it was the first-line therapy that affected overall survival. It will take more review. We’re all awaiting the results of the CALGB-80405 study.
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Charles S Fuchs, MD, MPH |
| Myeloproliferative Disorders Program Director Center for Gastrointestinal Cancer Dana-Farber/Harvard Cancer Center Professor of Medicine Harvard Medical School Boston, Massachusetts |
The results of the FIRE-3 study have not altered my practice. The study was relatively small to assess front-line therapy. The primary endpoint was investigator-assessed response rate, which was unusual. The current belief among oncologists is that cetuximab confers a better response. So this could have resulted in a bias.
It is also curious that the median duration of therapy was about 5 months, which is short. The overall survival curves did not separate until 12 to 15 months after treatment and showed a 3.7-month survival benefit in favor of cetuximab. It’s possible that therapy in the later-line setting influenced the results. It’s an interesting study but is controversial. I have no doubt it will be discussed at the upcoming NCCN meeting, and I’m not sure what effect the results will have.
The CALGB-80405 study evaluating cetuximab and/or bevacizumab with combination chemotherapy for patients with mCRC is a well-powered study and has overall survival as its primary endpoint. The findings from that study are now all the more important.
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Richard M Goldberg, MD |
| Professor of Medicine Physician-in-Chief, OSUCCC - James Cancer Hospital and Richard J Solove Research Institute Klotz Family Chair in Cancer Research The Ohio State University Columbus, Ohio |
In the FIRE-3 study, patients were randomly assigned to receive first-line FOLFIRI/bevacizumab versus FOLFIRI/cetuximab, but they received it for an average of only 5 months after treatment. No difference was observed in the response rate and in progression-free survival, and yet a 3.7-month difference was observed in overall survival. The investigators did not report on later lines of therapy. My analogy to this is that treating mCRC is like a baseball game, in which you have multiple innings. If I were in during the first inning and made a hit that drove in a run, I might claim that my team won the game because of my performance in the first inning. But it’s likely that all of the innings in the game are relevant to overall survival. As I commented at the ASCO press conference, I would like to see more data about second-, third- and fourth-line treatment for these patients.
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Axel Grothey, MD |
| Professor of Oncology Department of Medical Oncology Mayo Clinic Rochester, Minnesota |
The results of the FIRE-3 study have swayed me away from using cetuximab in a setting in which the need for a response is serious. I’m critical about the overall survival data, which showed a separation in curves after about 2 years in favor of cetuximab without any significant difference in investigator-assessed overall response rate and progression-free survival. It is difficult for me to believe that the difference in overall survival is related to the short duration of first-line therapy.
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Howard S Hochster, MD |
| Attending Physician Associate Director (Clinical Research) Yale Cancer Center Professor of Medicine Yale School of Medicine New Haven, Connecticut |
I am less likely to use cetuximab as first-line therapy in view of the data from the FIRE-3 study at ASCO 2013.
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Herbert I Hurwitz, MD |
| Associate Professor of Medicine Division of Hematology/Oncology Clinical Director, Phase I Program Co-leader, GI Oncology Program Duke University Medical Center Durham, North Carolina |
I don’t believe that the data from the FIRE-3 study are mature enough to change my practice. The data suggest that bevacizumab and cetuximab regimens have similar efficacy. But as a single binary choice, bevacizumab still appears better as a first-line agent.
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Wells A Messersmith, MD |
| Professor and Director GI Medical Oncology Program Co-Leader, Developmental Therapeutics Program University of Colorado Cancer Center Aurora, Colorado |
No, it will not, because I question whether a bias exists in the recommendations for second-line treatment in that trial. We’re awaiting the results from more mature data to be presented later.