This is a study that tests a new immunotherapy for the treatment of metastatic triple negative breast cancer. Triple negative breast cancer is a difficult type of breast cancer to treat; it’s one of the subtypes, the subtype, that really has no currently approved targeted therapies in the United States. It is negative for both the oestrogen and the progesterone receptor as well as HER2 so endocrine therapy and HER2 targeted therapies will not be appropriate for those particular patients. As a result we’re only left with chemotherapy with which to treat these women. Triple negative breast cancer tends to be somewhat more aggressive than other breast cancer subtypes as well and that combination of factors make triple negative breast cancer really an unmet medical need for better therapies for women.

Why did you go for checkpoint inhibition and why specifically this PDL1 agent?

Triple negative breast cancers are a particularly attractive target for cancer immunotherapy. They are characterised by a higher frequency of tumour infiltrating lymphocytes than most other breast cancer subtypes. These are the types of immune cells that can lead to an immune response against the cancer and cause tumour rejection, making them candidates for more likely response to an immune based therapy. Triple negative breast cancers tend to have more mutations than other breast cancer subtypes as well, that creates an opportunity for the cancers to prevent  very new, novel proteins to the immune system that it can recognise as foreign so they may be more easily recognisable by the immune system than other breast cancer subtypes. Finally, triple negative breast cancers are more likely to express PDL1 within the tumour, that’s the target of this new monoclonal antibody drug, MPDL3280A. PDL1 is associated with a process that down-regulates the immune response and prevents the immune response from being able to cause a reduction in the tumour and tumour rejection.

So you’re basically fine-tuning the immune response, harnessing it without doing too much damage?

That’s exactly right.

What did you do in the study?

So this study was a phase Ia study that looked at this particular drug, MPDL3280A, in a variety of tumour types, including triple negative breast cancer. The study initially tested the drug at a variety of different doses to generate safety information as well as identify a dose and then undertook expansion cohorts in a variety of different solid tumours, including triple negative breast cancer. Initially for patients with triple negative breast cancer a certain level of PDL1 expression by the immune cells within the tumour was required for enrolment. In addition, patients had to have a good performance status as well as have measurable disease by RECIST and no evidence of autoimmune disease.

What did you find in terms of toxicity, safety and efficacy, importantly?

In 54 patients that are evaluable for safety and side effects the drug was actually generally safe and quite well tolerated. The most common side effects were fatigue and nausea, anorexia, very mild side effects, so generally patients enjoyed a good quality of life on this agent. There were some higher grade side effects that included skin rash and shortness of breath as well as adrenal insufficiency and then one case of a more severe form of inflammation of the lung called pneumonitis. From an efficacy point of view the overall objective response rate was 19% in a group of 21 patients that were evaluable for clinical response. Importantly, the 24 week progression free survival rate is 27%. This really sets this agent apart from chemotherapies where patients can initially respond but typically progress quite quickly through this. So it’s important to note that these responses can be quite durable.

So the immune system is locked in, it’s actually doing some work. What does this mean for doctors, do you think, right now?

Right now, these data are early and additional patients are being enrolled on this study. This dataset indicates that this type of an approach has great promise for triple negative breast cancer; it can induce objective responses, including complete responses, to the therapy that can be quite durable. That is really the advantage of this type of therapy. In addition it’s quite well tolerated and the true response rates and such will need to be borne out in larger trials that enrol very significant numbers of patients. But overall it shows great promise for a type of breast cancer that currently has no targeted therapy options and really is a tumour in search of a much more effective therapy than what we have currently with chemotherapy.

Finally, very briefly, do you think this is the beginning of immunotherapy for breast cancer?

Yes, I really do. Yes. I think immunotherapy will be the way of the future and in particular combinations of immunotherapy with other drugs that can support the immune system and even more effectively harness it in a synergistic way to further increase the response rates that we see with these agents and also support the immune system so that we maintain that durability and longevity of the response.