We know that before the advent of PARP inhibition as maintenance in the upfront setting, we already knew that primary debulking surgery should be the preferred option in advanced ovarian cancer patients compared with neoadjuvant chemotherapy followed by interval debulking. So we were curious to see if this was confirmed in the PARP inhibition era, also according to the BRCA mutation status...
We know that before the advent of PARP inhibition as maintenance in the upfront setting, we already knew that primary debulking surgery should be the preferred option in advanced ovarian cancer patients compared with neoadjuvant chemotherapy followed by interval debulking. So we were curious to see if this was confirmed in the PARP inhibition era, also according to the BRCA mutation status. And so we addressed this issue by a propensity match analysis of more than 200 patients per arm comparing BRCA wild-type patients and BRCA-mutated patients receiving primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery, and all the patients received PARP inhibition. What we realized is that still now in the PARP inhibition era, primary debulking surgery achieved better outcomes in terms of both progression-free survival, overall survival, overall survival too, which was quite expected. This is also true according to the BRCA status. So it’s true in the BRCA wild-type patients as well as in the BRCA-mutated patients. But also we look at the interaction between the BRCA status and the surgical approach. And what we found, which was unexpected, is that the effect of neoadjuvant chemotherapy is more detrimental in the BRCA-mutated population than in the BRCA wild-type. As if probably, yes, neoadjuvant is an option still now, but probably is not the best option in the BRCA-mutated patient because, yes, it’s true that the response to neoadjuvant chemotherapy may be better in the BRCA wild-type, but after, when they have to receive the PARP inhibition, probably there could be some biological reason, maybe a reversal of the mutation, that may reduce the benefit of the PARP inhibition following chemotherapy. So these data are preliminary, need to be confirmed, but are the first evidence suggesting that the neoadjuvant can be more detrimental in the BRCA-mutated than in the BRCA wild-type.
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