The importance of central pathology pCR review in an international multicenter neoadjuvant study in HER2 positive early BC

Dr Hans-Christian Kolberg - Marienhospital, Bottrop, Germany

Many researchers already know that the LILAC trial was the trial that led to the approval of kanjinti, or ABP-980, the biosimilar for trastuzumab. It was a neoadjuvant study in breast cancer and what many people maybe don’t know, and that is what we are presenting here, that the LILAC study was the first international multicentre study in the neoadjuvant setting in breast cancer that included a central pCR review. Almost every neoadjuvant multicentre study in breast cancer, especially international studies, didn’t in the past include central pCR reviews because it is really very difficult to transport the specimen all over the world to the central pathologist. You cannot send the whole block, you’re sending slices, and then the central pathologist says, ‘I don’t have enough slices,’ so you have to go back to the site. So it’s really hard work to do a central pCR review.

We were able to show that the central pCR review is essential if you’re using complex pCR definitions. So what we showed and what we presented here is that if you use only pCR in the breast as the pCR definition there’s no real discordance between central and local pathology. The more complex your endpoint becomes the more the discordance is and it goes up to 8% which is actually surprising because you would think pCR there’s no tumours there, it should be easy to see. But actually it obviously definitely is not because if you use pCR in the breast and no DCIS the discordance gets bigger and if you really use the clean pCR definition – no invasive tumour in the breast, no DCIS in the breast and no involved lymph nodes anymore after neoadjuvant therapy – the discordance goes up to 8%. That is why we, after those results, recommend including a central pCR review in neoadjuvant breast cancer studies.

Why is it not currently being used?

Because it’s horribly expensive and it’s really difficult. We had in both groups we lost about twenty patients from local to central pCR review and that is actually in the beginning we thought it’s bad that we lost those twenty patients. We had a lot of discussions here at the poster and people came up and said, ‘How did you do that? Losing only twenty patients?’ So it is really hard to do. You have to be in constant communication with your sites and you have to be in constant communication with the central pathology and it really makes a study, an international study that is expensive anyway, a lot more expensive. So actually people don’t do it because it’s expensive and if you don’t test it you don’t know the difference and then you’re fine with your local pCR result.

For the approval of that special biosimilar, ABP-980, in breast cancer it was crucial to use the central pCR review because in the local pCR review actually the results crossed the border of biosimilarity. In the central pCR review the results were well within the borders and so it was approved as a biosimilar. So if the sponsor had not in the beginning planned a central pCR review that would actually have endangered the results of the study and the approval of the drug. That is now, in my country, in Germany, the most prescribed trastuzumab, a lot more than the originator. So that was really important but people are not using it generally because it’s very expensive.

Is this commonly used globally?

Yes. In Europe we even have quotas for biosimilars. In the region where I work if there is an existing biosimilar for a biological we have to prescribe at least 30% of the biosimilar. And because there is no real rationale for giving one patient the biosimilar and one patient not there’s a lot of people who use only biosimilars for existing antibodies.

Anything you’d like to add?

We believe, and the results we showed today, we think it’s important not only to look at the primary endpoints of a study but to really go on datamining. If you have a good dataset you really should look at it and think what else is worth reporting because it may help people conduct trials and it may answer things. So what we want to encourage is look at your data and look if there is something else that can be reported because it may really help people.