The potential of PARP inhibitors in new cancer groups and in combination with other treatments

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Published: 18 Jun 2019
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Dr Jennifer Litton - The University of Texas MD Anderson Cancer Center, Houston, USA

Dr Jennifer Litton talks to ecancer at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting about using PARP inhibitors in other tumour types, outside of ovarian and breast cancer, and in combination with other treatments.

She explains that combinations with PARP inhibitors are particularly exciting with immunotherapy highlighted as a promising combination option.

This programme has been supported by an unrestricted educational grant from Pfizer.

Outside of ovarian and breast cancer we’re seeing very promising signals in other tumours such as the POLO trial we’re seeing in pancreatic cancer. We think there are other mechanisms in effect that may allow other tumour types such as lung cancer to have some responses to PARP inhibitors as well. Now that we have some cancers that we need to know different status of their metastatic tumour, their PD-L1 staining for immunotherapies and looking at mutations in their tumour is becoming much more standard, we’re going to find a new group of people, I hope, that might benefit from these drugs.

What should researchers in this area focus on in the next couple of years?

We’re seeing very exciting combinations with PARP inhibitors with multiple different agents. Whether it’s with immunotherapy because we’re seeing some different changes in the immune microenvironment of breast cancer when people are exposed to PARP inhibitors and we’ve had two trials start to present, the TOPACIO trial and MEDIOLA, among many others that are ongoing. So the PARP and immunotherapy question and story is still coming.

There are a lot of other combinations with other DNA damage repair that make a lot of sense when we start to really delve into the mechanisms of resistance to some of the PARP inhibitors. Whether we add it with radiation, whether we add it with other inhibitors of other pathways are all ongoing.

We’re really excited, we have two PARP inhibitors now that are FDA approved for metastatic breast cancer showing that these drugs are very similar as far as showing improvement in progression free survival and the quality of life improvement. But the ongoing research to expand who can potentially benefit outside of people with germline BRCA as well as expand the amount of time duration. We’re spending a lot of time also moving these into the early breast cancer looking at the pre-operative and neoadjuvant. Can it potentially replace chemotherapy in the future? I think that question is a worthy question to be asked.