Medicine Matters oncology

So in a very quick summary, there was a time to radiographic progression-free survival with adding ipatasertib to abiraterone in first-line castration-resistant prostate cancer. And this was supported with some early evidence of clinical benefit, in improvements in time to pain progression with no compromise on overall survival. The data is very reassuring, that we see a biological target attack with the biological drug with clinical benefits.

The drug's not available yet for prostate cancer. There were some side effects that need to be mitigated. Namely, blood sugar control and diarrhea being the main issues. And with experience, physicians and patients will know how to mitigate those.

The data is not yet submitted to the FDA or regulatory agency. So it's not ready for prime time and use in general prescribing patterns yet. But we'll definitely try to put all the data together and work out when the data will be best ready to be presented to the FDA for possible general use.

So this is clearly a drug that hits a specific target, the AKT inhibitor. The AKT can be activated in a number of different ways. And the most common way is loss of the PTEN.

We possibly also find other patients by expanding the biomarker portfolio, such as do patients with a PI3 kinase mutation, or an AKT mutation, benefit from this? So future work is trying to define other patients in other settings in prostate cancer that benefit. Whether we use it for metastatic hormone-sensitive prostate cancer, or in combination with other agents.

And that's a work in progress. At this stage, we've got a strong signal with the P10 loss. But we need to refine the biomarker.

We also note that patients who have PTEN loss by analysis of the genome, the DNA exome, if you have loss of the P10 at the exome level, had more of an impressive improvement in radiographic progression-free survival, with about a 36% decrease rate of progression. However, that was a subpopulation of the total study. It was a secondary endpoint. But again, encouraging news that if we get a more accurate biomarker, we may actually see and identify patients who are more likely to benefit.

So there's a new drug, in combination with abiraterone, for prostate cancer. And the very important question is, how does this fit in with our treatment armamentarium? With indications for using abiraterone in metastatic hormone-sensitive prior to the castration-resistant setting. Other patients may enter the castration-resistant setting having only had hormone therapy alone with ADT. Or docetaxel, like the IPATential 150 Study.

So a physician will actually have to think about whether this drug, when it becomes available, hopefully, where it fits into their treatment portfolio, recognizing we have a very complicated chessboard with many different drugs approved in different settings. The chemotherapy docetaxel is approved in hormone-sensitive and castration-resistant abiraterone and enzalutamide are both approved in hormone-sensitive and castration-resistant. So trying to work out how to play chess pieces on this ever-increasing chessboard is going to be a challenge.