For a patient with HER2-positive, ER-negative metastatic disease my first-line therapy would be trastuzumab and pertuzumab in combination with weekly paclitaxel. I recommend the addition of pertuzumab to all patients because it yields a survival benefit without a lot of toxicity.

My usual second-line treatment for patients in the same situation is T-DM1. I believe the difference between the patients who fare well on T-DM1 and those who don’t is their HER2 status. A patient must have HER2-positive disease to benefit from the drug. I can’t send the message strongly enough that if you haven’t checked a patient’s HER2 status in a while or you’re not absolutely certain about the expression levels in your patient, she should be sent for a biopsy.

Paclitaxel/trastuzumab/pertuzumab is my usual first-line therapy for a patient with HER2-positive, ER-negative disease. Many patients with HER2-driven disease will cycle through multiple HER2-targeted therapies that are options in this arena. The trick is to optimize long-term options for these patients.

I have adopted the use of pertuzumab because it has shown a progression-free survival advantage and is generally well tolerated. I can usually only access pertuzumab in the first line. It is harder to justify for patients for whom trastuzumab has failed in the adjuvant setting. That’s the reason for leading with pertuzumab, trastuzumab and a taxane for this patient who has not received prior therapy.

T-DM1 is my typical second-line therapy because its use is supported by the data. My second-line therapy used to be capecitabine/lapatinib. But if you have a drug like T-DM1 that overperforms and is less toxic, then I tend to adopt it. I reserve T-DM1 for the second line unless the patient experiences relapse during or immediately after adjuvant trastuzumab. If I had the opportunity to access it in the first line, I might use T-DM1 as a single agent for a patient who has low-burden, ER-negative, HER2-positive disease and use the THP triplet for more aggressive tumors. It is possible that T-DM1 is equivalent to dual HER2 targeting, but I suspect not.

I would consider trastuzumab and weekly paclitaxel with or without pertuzumab for this patient. The CLEOPATRA trial, which investigated the addition of pertuzumab to docetaxel and trastuzumab as first-line therapy for patients with HER2-positive metastatic disease, was supportive of the addition of pertuzumab. However, I find it difficult to determine who will benefit most from pertuzumab. We have attempted to determine whether patients with certain tumor characteristics would benefit from pertuzumab, but we’ve failed to identify such a population. The majority of patients will experience a response to taxane/trastuzumab, especially if they’ve received no prior therapy.

My preference for second-line therapy for patients with HER2-positive, ER-negative metastatic disease would be T-DM1. I can justify using it and can obtain approval for it in this setting. T-DM1 was shown to be more effective than lapatinib/capecitabine. Pertuzumab is not an option because I can’t get it covered by insurance outside of the first line.

I would administer trastuzumab/pertuzumab and weekly paclitaxel in this scenario. The CLEOPATRA trial demonstrated a survival advantage for patients who received pertuzumab in addition to docetaxel/trastuzumab as first-line therapy. I don’t know of any other option that is better than the combination of 2 antibodies and a taxane used in that study. I’ve administered it fairly often and found that the regimen is fairly well tolerated.

My preference for a taxane is weekly paclitaxel, which appears to be better tolerated than the docetaxel used in the CLEOPATRA study. The response rate to paclitaxel regimens in a nonrandomized Phase II study is high, so I feel confident that it’s a reasonable substitution.

My choice for second-line therapy for a patient with HER2-positive metastatic disease would be T-DM1, assuming she had received THP in the first-line setting. I believe T-DM1 is superior to capecitabine/lapatinib, which was standard second-line therapy.

I would choose trastuzumab/pertuzumab and weekly paclitaxel as first-line therapy for this patient because of the benefit observed in the CLEOPATRA study. I have found the paclitaxel regimen to be better tolerated than docetaxel and I’m generally more comfortable with paclitaxel in the metastatic setting. Paclitaxel can be continued longer than docetaxel. We now have safety data from a relatively small study indicating that it’s a feasible regimen.

The data from the EMILIA trial suggest that T-DM1 is the optimal second-line treatment, so that would be my recommendation in that setting. T-DM1 is better tolerated and has a significant survival advantage compared to lapatinib and capecitabine.

I would recommend trastuzumab, pertuzumab and weekly paclitaxel for a patient in this situation.

My choice for second-line therapy would be T-DM1. The data with T-DM1 indicate that it results in good disease control and longer survival with minimal toxicity.

My usual first-line therapy for a patient in this scenario would be trastuzumab/pertuzumab and weekly paclitaxel. I’ve used this regimen 4 or 5 times and have found it to be well tolerated.

For a patient with HER2-positive metastatic disease who has already received pertuzumab, my choice would be T-DM1 in the second line. I would consider T-DM1 in the first line for a patient whose disease recurred within a year of treatment with adjuvant trastuzumab and a taxane.

My preference for first-line therapy in this scenario would usually be trastuzumab/pertuzumab and weekly paclitaxel. However, if patients are working and/or have to travel some distance, I recommend docetaxel. The cumulative toxicity of docetaxel limits the number of cycles that can be administered, so for other patients I would opt for paclitaxel.

My recommendation for second-line therapy depends on what the patient received in the first-line setting. If she received THP in the first-line setting, based on the results of the EMILIA study, I would use T-DM1 in the second line. If her first-line treatment was T-DM1, then I would use a pertuzumab combination as second-line therapy.