DR BRUFSKY: This is very important, practically, for the clinic, mainly because basically what it shows, even though it’s a Phase II trial — there’s not comparative randomized data — the data that comes out of that are very similar to the experimental arm of CLEOPATRA when used with weekly paclitaxel. So this is basically TH/weekly paclitaxel. It gives a lot of people comfort that you can use weekly paclitaxel.
The issue was initially — and I think this is more important for a practical reason — that insurers would only pay for trastuzumab/pertuzumab and docetaxel. Now, I believe, based on this data or data like it, the NCCN formulary allows the use of paclitaxel. So physicians can use paclitaxel now with these drugs and get them reimbursed. We’ve been able to. And I’m assuming, because NCCN formulary is, most Medicare patients probably are able to get it reimbursed also. For that reason, that’s very practical data.
DR LOVE: I just want to go around the table a little bit and get some input from you in terms of how you’re using pertuzumab right now in your own practice. Ruth, maybe you can talk a little bit about in what situations you’re thinking about pertuzumab, what you combine it with and how you feel about using it in later-line therapy.
DR O'REGAN: Pertuzumab/trastuzumab and docetaxel would be my first-line treatment of choice. The bigger question is: Can we get it paid for in the later stages? Because we have Phase II data without chemotherapy with pertuzumab and trastuzumab showing activity. And I’ve been successful in some patients in getting it, but I think that’s going to be a question going forward.
DR LOVE: Sara, how are you using pertuzumab?
DR HURVITZ: We cannot get it beyond the first-line setting. It’s a real struggle.
DR LOVE: Hope, how do you use pertuzumab?
DR RUGO: Also first line. I mean, we’re both in California where reimbursement, I think, is a little more challenging than many other places in the United States. And I’ve found that, depending on the type of insurance, we can’t authorize trastuzumab/pertuzumab in combination. And based on the data recently published from the earlier-phase trial, it appeared that even in patients who were progressing on chemo and trastuzumab, that that combination was effective and was not associated with significant toxicity. So I’ve been able to give it to a few patients, but not many, when that was a reasonable option to go with antibody therapy alone.
Otherwise, the NCCN in the most recent guidelines, I think, is agnostic in terms of type of taxane and also allows first and second line. So that’s very helpful. I think that we can get approved first and second line without any difficulty. If I have a patient with a private insurer who’ll approve it, I’ll give it late line because based on that Phase I trial — Phase I/II, essentially — it suggests that that combination works even in patients progressing on trastuzumab. I think that survival benefit in the CLEOPATRA trial is very compelling.
DR LOVE: Can you comment on the magnitude of benefit in survival data?
DR RUGO: I think the magnitude of survival is really impressive. The hazard ratio is 0.66. It’s a 34% relative improvement in survival. If you project out, of course, it continues to widen, which is, I think, intriguing because in that trial you couldn’t cross over.
DR LOVE: Adam, are there situations where you would use hormone therapy/trastuzumab and pertuzumab without chemo?
DR BRUFSKY: I’d like to be able to do that on study. The PERTAIN study — it’s aromatase inhibitors/trastuzumab versus aromatase inhibitor/trastuzumab/pertuzumab — but you’re allowed to give paclitaxel for 3 months before, or 4 months before, if you want.
DR LOVE: So, just to ask you the same question I’ve been asking other people: In what situations do you use pertuzumab?
DR BRUFSKY: I would use THP, I think, initially, like most people, with docetaxel. The data now from Memorial — I have no problem up front, giving it with paclitaxel if I had to. And I have no problem giving it in later lines. I mean, I think that unfortunately we’re repeating all the mistakes we did with trastuzumab 10 years ago — not doing it beyond multiple lines. I wish we had data on later lines to show the insurance companies.
And I’ve had no problem getting it paid for, actually, beyond first line because of the NCCN coming out in — I think it was September — with their statement, so I use that against my insurers. But I don’t live in California, so that’s kind of tough.
DR LOVE: Same question to Edith: How do you use it and which chemo?
DR PEREZ: I prefer the first-line regimen. It’s actually participation in a trial that is called the VELVET trial. This is a global Phase II study we’re doing looking at vinorelbine/trastuzumab and pertuzumab. We have 2 cohorts of patients. In the first cohort, they get one drug and then the other and the other. We have completed that cohort of patients already.
In the second cohort, the patients will get vinorelbine. And then in one single IV bag they get the combination of trastuzumab plus pertuzumab. We’re looking at safety and efficacy with the idea that if we can show that we can combine the 2 antibodies in 1 IV bag, it will save time for our patients. And I think using vinorelbine instead of a taxane, it’s actually very compelling along with anti-HER2 therapy.
DR LOVE: For efficacy or toxicity?
DR PEREZ: Both.
DR LOVE: Same question to you, Lisa.
DR CAREY: I’ve typically used it first line. And I’ve used it with both docetaxel and with weekly paclitaxel, both ways. I have used it only once later line, but it was a compelling circumstance of a patient who I’ve been managing for several years with metastatic HER2-positive, hormone receptor-negative breast cancer, who has liver-dominant disease — symptomatic liver disease. And every time I give her a HER2-targeted agent, the liver disease shrinks down, her symptoms go away. It lasts for 10 to 12 months. It comes back. She comes with a visible mass and saying, “Oh, my stomach hurts again.” I change the HER2-targeted. I tweak it. First it was trastuzumab, then I added lapatinib. I’ve been tweaking. And I was running out of tweaks to do the last time that she came in, and it was right after pertuzumab was approved. I got approval for her to get — I’m almost embarrassed to say — she’s on gemcitabine/trastuzumab/pertuzumab as her fourth- or fifth-line HER2-targeted therapy. Her liver tumor went down and her symptoms went away.