Camille Hertzka, vice president and head of oncology, US Medical, AstraZeneca, speaks on how the OlympiA findings may warrant greater need of genetic testing for BRCA mutation and the efficacy of olaparib by patient subgroup.
With olaparib shown to be an effective treatment option in early breast cancer, all patients should then be tested for the genetic BRCA mutation as soon as possible, said Camille Hertzka, vice president and head of oncology, US Medical, AstraZeneca.
Are there patients who are not receiving genetic tests that should be receiving them in light of the results of OlympiA? How early should genetic tests take place?
I would say that all patients with breast cancer should be tested for a genetic BRCA mutation. And I would say even further, it's not only related to the OlympiA data, it is even further now, but it has been the case over the past year. As soon as we identified the BRCA mutation, that the BRCA mutation and the BRCA segments were going to drive a different biology in breast cancer, it became something important to look for.
So, it's important because it's a different biology, it's a different prognostic for patients. So, from a natural history of the disease, it's important, but what is very important is that it's a genetic mutation, which means that there is an increased familial risk of developing a cancer. And so it's important to do the test for the patient, but also for their family.
So, I would say, regardless of anything else, it's a critical step that should be done. And we see actually relatively high testing rates when we look at testing today of BRCA in the earlier stage of breast cancer.
Now, that needs to be improved, so we need to continue to raise awareness of the family implication of BRCA about the fact that this is really a different disease. It's one breast cancer within the groups of breast cancer. And if everybody starts to understand how distinct his disease is, that is going to really drive even further testing.
Now, as soon as OlympiA data will be approved and will have a regulatory approval, then it will be another story, because on top of being a distinct biological disease, there will be a treatment option for these patients that is going to improve their outcome.
So, yes, I think that there's still a lot to do, but there are so many good reasons for testing that I hope it's going to happen very quickly. And the question on how early: as early as possible.
Can you estimate how many more breast cancer patients would be candidates for olaparib based on these results?
So, that's always a very difficult question, because it's an estimation obviously. So, if we look at the number of patients that we estimate having triple-negative breast cancer (TNBC), who could be treated in this early stage, we think about 17,000 patients in the United States—knowing that 16% of them should have a BRCA mutation. So, that's the estimation we would have for this subgroup.
If we look at the HR-positive [hormone receptor-positive] group of patients, here it’s a larger group of patients, it's more frequent, we have 165,000 patients in the United States being HR-positive. Out of this 165,000, we estimate 5% of BRCA mutation.
So, HR-positive breast cancer is more frequent, but less BRCA mutation in this group than in patients with TNBC. If we were looking at the absolute number that we would have, it would probably be still bigger with the HR-positive patients just because of the higher incidence of HR-positive breast cancer.
Were there any subgroup results that were noteworthy?
Going back then on the data of the OlympiA study, and I have to talk about this because I find this data very important to remember, so if you look at the primary end point of the study, which was IDFS [invasive disease–free survival], for olaparib vs placebo, we have a hazard ratio of 0.57, and that is in the ITT [intention to treat population].
To answer the question that you have on subgroups. The benefit was observed across all the different subgroups that we had in the study. Also, again, that's an exploratory analysis, but the one thing that I thought was interesting is a sensitivity analysis that was planned from the very beginning for this interim analysis.
Because we knew that a 2.5 year follow-up, although was a lot, was potentially a question that we could have, in terms of is it enough for breast cancer, there was a pre-plan sensitivity analysis, which was looking at the first patient enrolled in the study that would have 3.5 years of follow-up, and that represents a group of 900 patients.
So, for that group, we have therefore more measured data and full data that would feel very comfortable with. And the good news here that we observed was that the hazard ratio was very similar with 0.61. So, very, very consistent, which reassured us that the hazard ratio we see in the ITT population is real, it's really happening.
So, that's a very important analysis, which is not exactly a subgroup analysis, as usually you would say, but it's still a subgroup analysis.
Tutt ANJ, Garber JE, Kaufman B, et al; OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. Published online June 3, 2021. doi:10.1056/NEJMoa2105215