DR RUGO: So this agent is a proposed trastuzumab biosimilar. And the regulatory agencies, the FDA and the EMA, have developed regulatory guidelines for getting approval of biosimilars. So the first question is what a biosimilar is. And we think about the generics we see all the time — letrozole, aspirin, for example. And these are generally simple chemicals that are easy to reproduce. And you can show that they’re structurally identical and believe, for that reason, that they will also be identical in clinical practice.

The biosimilars really represent a group of complex chemicals, usually targeted biologic agents or supportive care agents such as pegfilgrastim or filgrastim. And they require a much more complicated development and synthesis. And also, it’s, for that reason, in order to say, “Okay. These are complicated agents, so now we want you to reproduce all of the original data.” Obviously you’d never get a drug out there, because that would be cost prohibitory and patient prohibitory. And it’s important for people to understand that issue.

But we need biosimilars, because we need competition for these drugs when they go off patent. Otherwise, the drugs will continue to be very expensive and not available to patients around the world. What we recognized is that trastuzumab is available only to some parts of the world, because of its expense. It really makes it unattainable for many patients and/or they can only be exposed for a short period of time. So the goal with biosimilars is to provide alternatives. What cost they will have? We don’t know. But we know that competition is a good thing.

So we started this trial actually now almost 6 years ago, where we wanted to look at this particular proposed trastuzumab biosimilar. We chose the first-line setting in metastatic disease as our area to study and randomized patients to receive trastuzumab and taxane of choice by institution or the proposed trastuzumab biosimilar and taxane of choice. The regulatory guidelines allow us to have a short-term outcome, overall response rate.

And if the drug has passed all of these hugely complex prior studies, showing structural/physical similarities, similar PK, similar antidrug antibodies, et cetera, et cetera, then the overall response rate is taken as proof that this drug is similar. So our overall response rate at 24 weeks was identical between the 2 arms, essentially. We showed no difference in adverse events or effect on heart function and no difference in immunogenicity. There also was a separate pharmacokinetics study showing exact similarity in healthy adults. So we will continue to follow patients for progression-free and overall survival out to 48 weeks, but the 24-week endpoint is our primary endpoint. And that was the data that we submitted, that will be submitted to regulatory agencies.

Now, there was also a biosimilar for bevacizumab that was presented as a poster session for lung cancer and also showed equivalency. And there’s already an approved biosimilar for filgrastim but not for targeted agents in cancer. There are approved biosimilars for autoimmune diseases out there that people are using based on these kinds of efficacy data.

DR LOVE: Do you think that you can just take this data and widely apply it? And, for example, would you have any concern about using, let’s say, this trastuzumab biosimilar in the adjuvant situation where you’re trying to cure somebody?

DR RUGO: I feel that based on this data and all of the similar physical and immunologic characteristics that it would be safe to use this as a substitute for trastuzumab. And I think that in most places where this will be used, the option will be no therapy or trastuzumab. And by the time the patent runs out in the United States, where patients have access to trastuzumab sometimes for a decade, because they have metastatic disease or have no disease, no progression, that this will come to us after there is a lot more safety data even obtained. And people will feel more confident with the whole idea of biosimilars by that time.

Genomic assays and (neo)adjuvant treatment decision-making

Early-stage breast cancer in the adjuvant and neoadjuvant settings

Management of metastatic breast cancer (mBC)

CDK4/6 inhibitors for the treatment of breast cancer

Checkpoint inhibitors and other novel immunotherapeutic approaches to breast cancer

Triple-negative and BRCA mutation-positive breast cancers