Are there situations in which you would use T-DM1 combined with pertuzumab outside of a trial?
If a patient had not received pertuzumab in the first-line setting, would you use it in the second line or beyond? If so, in what situations would you use it?
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Kimberly L Blackwell, MD |
| Professor of Medicine Director, Breast Cancer Program Duke Cancer Institute Durham, North Carolina |
I would not recommend T-DM1 combined with pertuzumab outside of a trial. I’m awaiting the results of the MARIANNE study that is comparing T-DM1 with pertuzumab to trastuzumab and a taxane for patients with metastatic breast cancer.
I would administer a course of pertuzumab and a taxane in the second line and beyond if I could get it covered by insurance in patients who have not previously received it.
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Lisa A Carey, MD |
| Richardson and Marilyn Jacobs Preyer Distinguished Professor for Breast Cancer Research Chief, Division of Hematology and Oncology Physician-in-Chief North Carolina Cancer Hospital Associate Director for Clinical Research Lineberger Comprehensive Cancer Center Chapel Hill, North Carolina |
I would not administer T-DM1/pertuzumab off protocol. I believe this is an interesting combination and I’m looking forward to the data from the MARIANNE trial.
I tend to use drugs in the manner in which they have been approved. If I could access pertuzumab or T-DM1 in any line I would be more free form. For a patient who had low disease burden, I would use T-DM1 early in treatment. If a patient had a low platelet count, however, I might not choose T-DM1.
It would be interesting to see the data comparing the efficacy of trastuzumab/pertuzumab and a taxane to that of T-DM1. My guess is that dual targeting will play a role in the treatment of HER2-driven cancer. I incorporate trastuzumab/lapatinib regularly into my practice. I have had patients who have been through 4 or 5 different permutations of anti-HER2 therapies. For some of them, that’s the path to the longest disease control.
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Julie R Gralow, MD |
| Professor, Medical Oncology Jill Bennett Endowed Professorship in Breast Cancer University of Washington School of Medicine Director, Breast Medical Oncology University of Washington School of Medicine/Seattle Cancer Care Alliance Member, Clinical Research Division Fred Hutchinson Cancer Research Center Seattle, Washington |
I would not use T-DM1 combined with pertuzumab outside of a trial. I’m awaiting the results of the MARIANNE study.
If I could access pertuzumab I would use it in the second line and beyond. We don’t have approval for it in these settings currently, but I see no reason why it wouldn’t work. I believe it will eventually be approved as later-line therapy.
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Clifford Hudis, MD |
| Chief, Breast Cancer Medicine Service Solid Tumor Division Department of Medicine Memorial Sloan-Kettering Cancer Center Professor of Medicine Weill Cornell Medical College New York, New York |
I would not use T-DM1 combined with pertuzumab outside of a trial.
I have used pertuzumab in the second line and even beyond many times. In fact, this is permitted according to the NCCN guidelines. No reasons are apparent that pertuzumab wouldn’t work as later-line therapy. Early drug development data suggest it is effective in these settings. I believe patients deserve one shot at pertuzumab, even if it’s not in the first line.
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Ian E Krop, MD, PhD |
| Associate Physician Dana-Farber Cancer Institute Assistant Professor of Medicine Harvard Medical School Boston, Massachusetts |
I would not administer T-DM1 combined with pertuzumab outside of a research setting because currently no data show that it would have additive benefit. I’m looking forward to the results from the MARIANNE study.
I would consider treatment with pertuzumab in conjunction with trastuzumab and chemotherapy in the second-line setting and beyond if a patient had not received the drug previously. While we do not have randomized data confirming a benefit to pertuzumab in later lines of therapy, we do have a small Phase II study indicating that the combination of pertuzumab and trastuzumab is active in this setting. Based on this result and the observation that the benefit of other HER2-directed agents has not been dependent on line of therapy, I believe it is reasonable to consider this combination in a later line for patients who have not previously received pertuzumab. I don’t, however, use it more than once.
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Kathy D Miller, MD |
| Co-Director, IU Simon Cancer Center Breast Cancer Team Ballvé Lantero Scholar in Oncology Associate Professor of Medicine Department of Personalized Medicine Division of Hematology/Oncology The Indiana University Melvin and Bren Simon Cancer Center Indianapolis, Indiana |
I would not use T-DM1 combined with pertuzumab outside of a trial because we don’t have clinical trial data demonstrating that the combination is superior. A Phase II trial of T-DM1 and pertuzumab shows that this combination yields a shorter progression-free survival compared to the pertuzumab/trastuzumab/docetaxel regimen from the CLEOPATRA trial. This may be an unfair cross-trial comparison in some ways, but we have no Phase III data and the imperfect cross-trial comparisons that we have don’t suggest that it will be better. The data from the MARIANNE trial may suggest otherwise, but currently I would not recommend this approach.
If I could access pertuzumab in later-line settings, I would use it. It would be a shame for women with HER2-positive disease to die without having a chance to benefit from pertuzumab therapy just because they had the misfortune of having gone through the first-line setting before the drug was available.
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Joyce O’Shaughnessy, MD |
| Co-Director Breast Cancer Research Program Baylor-Charles A Sammons Cancer Center Texas Oncology US Oncology Dallas, Texas |
I would not recommend T-DM1 combined with pertuzumab outside of a trial because I would not be able to get it covered.
If I could access pertuzumab, I would want to use it as soon as possible because of the benefit observed in the CLEOPATRA study. If a patient has not received pertuzumab previously, I would use it in the second-line setting and beyond.
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Hope S Rugo, MD |
| Professor of Medicine Director Breast Oncology and Clinical Trials Education University of California, San Francisco Helen Diller Family Comprehensive Cancer Center San Francisco, California |
I would not administer the T-DM1/pertuzumab combination outside of a research setting. It would not be covered by insurance and it would be impossible to justify in the absence of randomized clinical data.
I would consider pertuzumab in the second-line setting and beyond and have argued strongly for it since it was approved. In a Phase I study trastuzumab and pertuzumab were effective for some of these patients. Interestingly, in my practice, I haven’t seen it work in the majority of patients in the late-line setting. However, the patients to whom I’ve administered it had particularly resistant disease.