AstraZeneca VP, Head of Medical Affairs, US Oncology, Discusses the Impact of PARP Inhibitors on Cancer Treatment

PE: Overall, can you discuss the impact that PARP inhibitors have had on the cancer treatment landscape?

Doti: I think PARP inhibitors change several ways of how we think cancer. First of all, it’s not just treating directly to a mutation that impacts the growth of a cancer or just blindly impacting the cancer growth like chemotherapy, but actually synergizing on mechanism of repairs by sensitizing the cell with chemotherapy and then using the PARP inhibitor to have long standing responses. That’s why you can use it as a maintenance of an already accomplished response or in combination with another drug in first line ovarian cancer.

Second thing I also mentioned is that mutation that affects the family members beyond the case that is in discussion, that is not unique to BRCA, but it was inaugurated with BRCA, and now we see a lot more of this kind of thinking into oncology, both in solid tumors and in hematological tumors as well. So, I think that it's definitely a tipping point for us in oncology as a whole, by bringing this different kind of thinking when we decide the treatment of a patient and how we impact the whole family members around that. Which it was done before, but not to the extent that we’ve seen it’s been done today.

PE: Can you briefly speak about the history of LYNPARZA® (olaparib)? Specifically, what caused it to lay dormant for so long and what influenced AstraZeneca to keep working on the drug’s development?

Doti: When you're marking drug development, you know this is a journey for years. We have a very conscious decision as a company that we don't develop drugs in isolation. It’s not because we found another mechanism of action or we acquire a company, we just go in that place, and then we move to the next. So, if you see our history in the last 10 years, we decided to go into specific areas of unmet needs such as lung cancer, breast cancer, gynecological cancers, genitourinary gastrointestinal cancers and hematology. And in each of these therapeutic areas that we go, we go all in, right? For us, LYNPARZA was the first of the second generation of drugs that we developed. It helped us and taught us so many things into how to do clinical development here. That’s where we started with second line ovarian. We moved to first line combinations in ovarian. We went also in advanced setting in breast cancer and we also went in the adjuvant setting, which is the other thing that we've learned from LYNPARZA and others to do more. Everything that we do in AstraZeneca we start with the biggest unmet need, which is usually in second line following metastatic, but we want to make sure that we bring our drugs to every single patient that may benefit from it. So, if you see our portfolio, everything that we do, we try to go as early as possible and that is the proof for LYNPARZA both in ovarian and in breast and also in prostate.

Now, if I may, move this a little bit for more personal, LYNPARZA was one of the reasons that I joined AZ eight years ago, and this month is my eight-year anniversary so I’m still celebrating until the 31st of July because when I saw what we can do with this science, we saw that AstraZeneca was thinking oncology in a different way. Although we were not acknowledged as the big players that we are known as today back in 2014, I always thought this is the kind of approach that we need to have. It’s not just solving one indication for a drug, it’s how to solve the patient journey as a whole and LYNPARZA has a lot to do within science today in AstraZeneca.