Expert Predicts the Trajectory of Biosimilars in Oncology

Haythem Y. Ali, MD

Several biosimilars for trastuzumab (Herceptin) are under investigation, with one achieving an FDA approval at the close of 2017. The FDA approved MYL-1401O (Ogivri; trastuzumab-dkst) for use in HER2-positive breast cancer, as well as HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.

Data from the phase III HERITAGE trial presented at the 2018 ASCO Annual Meeting showed that adding MYL-1401O (Ogivri; trastuzumab-dkst) to a taxane as initial therapy followed by MYL-1401O monotherapy as maintenance produced a nearly identical progression-free survival (PFS) rate at 48 weeks compared with trastuzumab (Herceptin) in patients with HER2-positive metastatic breast cancer.¹

Through 48 weeks, the PFS was nearly identical between the 2 arms at 11.1 months (P = .842) with similar confidence intervals (MYL-1401O, 8.81-11.20; trastuzumab reference, 8.60-11.20). HR stratified by assigned taxane, tumor progression, and tumor endocrine status for 48-week PFS was 0.95 (95% CI, 0.714-1.251; P = .694).

Data from a separate abstract presented at ASCO showed that the bevacizumab (Avastin) biosimilar PF-06439535 demonstrated similarity to the EU bevacizumab reference product for overall response rate (ORR), with similar pharmacokinetic and immunogenicity profiles for the frontline treatment of patients with advanced nonsquamous non—small cell lung cancer.

Results from the ongoing double-blind, randomized trial (NCT02364999) showed that the ORR at 19 weeks (confirmed by week 25) in the intent-to-treat population, the primary endpoint of the trial, was 45.3% (95% CI, 40.01-50.57) for PF-06439535 combined with paclitaxel and carboplatin compared with 44.6% (95% CI, 39.40-49.89) for bevacizumab-EU combined with paclitaxel/carboplatin.²

The success of these agents may be signaling a future role for biosimilars as a whole in cancer care, said Haythem Y. Ali, MD.

OncLive: How will you decide whether to give standard trastuzumab or a biosimilar?

In an interview with OncLive, Ali, a senior medical oncologist at Henry Ford Hospital, discussed the state of biosimilar development and implementation in the field of oncology.Ali: I believe that a lot of this decision making is probably going to be taken out of our hands completely, and we will be told which one to use by payers. And, I think that is fair. One has to understand biosimilars and not be afraid of them. The FDA has put together very nice rules to determine what biosimilar is considered an effective biosimilar and which is one is not. If the producers of biosimilars meet those criteria, it is really not fair to discriminate against them.

There is one thing that gives me some pause. In the metastatic setting, it is easy to see whether something is working or not, because you have a way of monitoring the patients and their response. Therefore, it is not going to be hard for you to figure out if something is working out or not. I have some trepidation in the adjuvant setting and even the neoadjuvant setting. In the adjuvant setting, you are sort of taking a leap of faith, and you have to be really comfortable with that medication before you give it without fear or discomfort.

Is there any rationale for conducting studies of biosimilars in the adjuvant setting?

Is there anything that regulatory agencies, investigators, or institutions can do to ease the transition of biosimilars into mainstream cancer care?

Are there any clinical trials of other biosimilars that look promising?

Do you foresee biosimilars having a larger role in oncology over the next decade?

I would say that initially, we will use it in the metastatic setting, start feeling comfortable that it is doing what it is supposed to, and then once we gain more comfort, it will be much easier to accept it as an adjuvant treatment, as well.The problem with adjuvant studies is that they take such a long time to figure out. If you mandate adjuvant studies before you use it, we will never get a single biosimilar. This is because by the time that we answer the question, we will have moved on to other adjuvant therapies. It is reasonable to make sure that the efficacy is reasonable in the metastatic setting, and once you are comfortable with that, you should be comfortable prescribing it in the other setting that the reference drug is approved for. It is a personal comfort, and it shouldn't take us long to figure out whether these drugs really do what they are saying. We should be able to answer the remaining questions with a few metastatic patients.There are some providers who may be thinking of them like generics, but they have a different name. [We need] more education about why the name is different, why we need these different sets of rules, and why these rules are good enough to tell us that the drugs are working. It is more education than anything. Last year, I was at the 2017 ESMO Congress and there was a session with 4 different biosimilars of trastuzumab, and the studies were exactly the same. There are a lot of biosimilars out there all targeting the same thing—bevacizumab (Avastin), trastuzumab, and rituximab (Rituxan)—every biologic that you could possibly think of will have a biosimilar. There will always be innovation. I can't imagine it being only biosimilars, but how many of us are actually using branded tamoxifen? We are not. These old biologics are probably going to be replaced by biosimilars. However, new biologics will come in. That is part of innovation.

References

1. Manikhas A, Pennella EJ, Bondarenko I, et al. Biosimilar MYL-1401O monotherapy versus trastuzumab monotherapy after combination therapy: Toxicity, efficacy, and immunogenicity from the phase 3 HERITAGE trial. J Clin Oncol. 2018,36 (suppl; abstr 110).
2. Socinski MA, Von Pawel J, Kasahara K, et al. A comparative clinical study of PF-06439535, a candidate bevacizumab biosimilar, and reference bevacizumab, in patients with advanced non-squamous non-small cell lung cancer. J Clin Oncol. 36, 2018 (suppl; abstr 109).