Arjun Pon Avudaiappan: And thank you for the opportunity to share our findings with the audience. So it's a real great opportunity for us.
Zachary Klaassen: Awesome. We're excited to have you here because I think this is really important. The discussion around how low should the PSA get. Why is it important to try to get PSAs less than 0.2?
Arjun Pon Avudaiappan: 0.2 has been traditionally the baseline expected nadir value in the treatment of prostate cancer for quite a long time over decades. Maybe after radical prostatectomy or during the follow-up treatment with ADT, often it has been 0.2 has been set as a cutoff and it has been the targeted value to say the response has been good and the patient's outcome are being improving and it has been proven quite well in many of the studies.
So over decades now the treatment intensification has happened where many other multimodal treatments has come up for patients with metastatic hormone-sensitive prostate cancer to say with ADT in combination with the ARPIs or an ADT, ARPI and docetaxel, what we called as a doublet and triplet therapies.
But how is that still the baseline of 0.2 is being? Is it effective or not was one of the question that has been recently being rose around the situation? So you wanted to keep 0.2. And add it and check how it goes through.
Zachary Klaassen: Yeah, it's a great background. So I know you did an extensive systematic review of meta-analysis. Maybe just walk our listeners through the methodology for this analysis.
Arjun Pon Avudaiappan: We looked into the databases like PubMed, Embase and other Cochrane databases and we looked into all the randomized controlled trials, which has been reporting about the 0.1 value as one of their post-hoc analysis or being one of the part of their primary analysis part.
So we individually extracted those studies which have been reporting it and we wanted to give and substantiating additional evidence to those to say that does the poll analysis still demonstrate the same effectiveness as individual studies has been responded? So that was the initial point of the starting.
Zachary Klaassen: Excellent. So walk our listeners through the results because it's important results. You looked at all these trials and how many patients, how many trials, what were the hazard ratios you guys found?
Arjun Pon Avudaiappan: So the hazard ratio was around say to say 0.02 to point, we are looking into different parts of the oncological outcomes like the progression-free survival, the overall survival, the radiation [inaudible 00:02:39], and the PSA response survival and the castration sensitive resistant progression. So looking at all the points, we were able to come to an average hazard ratio between 0.19 to 0.35 somewhere around.
So that was looking quite significant findings saying around say there's a 70% response and with the better survival outcomes in patients assuming those with the 0.2.
Zachary Klaassen: Yeah, that's fantastic. I know when I was looking at this, it struck me that these hazard ratios 0.2, 0.22 compared to the intention to treat population where we know these drugs all work very well, hazard ratio is about 0.6, 0.7. What's the message to our patients based on your guys' findings and the importance of PSA less than 0.2?
Arjun Pon Avudaiappan: We have been looking at the previous historical studies, which is showing that 0.2 has been the ideal cutoff to say there is a good response and not like and the patient might have been progressing and this meta analysis as well showed in spite of the patients who was either only the ADT or an ADT in combination with other therapies, still 0.2 had a good cutoff to say whether the patient has a good response or the patient might have good chances to progression.
So recently we could see many studies coming up saying that the serum PSA with a deep response and alternative response kept setting a cutoff at 0.2 and less than 0.02 to see the impact of these combined therapies of doublet and triplet therapies. So this significantly says that when the patients are able to reach below 0.2 or 0.02, they have much better survival outcomes compared to patients who are much more than that.
So this plays an important role to help us in deciding whether the patient needs an escalation or a de-escalation of treatment. That way we can also limit the exposure to the additional treatment modalities for these patients.
Zachary Klaassen: Yeah, it's a great answer. I think that's really important to know. The patients see the PSAs in the chart that can track it. We know the importance of less than 0.2 and as you said, 0.02. This has been really nice conversation to really highlight this. Any take-home messages or concluding statements for our listeners?
Arjun Pon Avudaiappan: Over years, serum PSA has been our traditional biomarker and we have been using it for radical prostatectomy and also on follow-up on various treatments and still even with evolution of the further treatments like doublet and triplet therapy, still serum PSA, which is ideal screening tool which has been earlier being used and which are one of the easier modalities and easily accessible biomarkers is available. It still holds as a good biomarker for patients in these multimodal treatment as well.
Zachary Klaassen: Yeah, well said. Arjun, congratulations on the great work in the presentation at ASCO this week.
Arjun Pon Avudaiappan: And I would like to thank my team as well.
Zachary Klaassen: Absolutely.
Arjun Pon Avudaiappan: Which is Dr. Mohammed Arfat Ganiyani, who's also associated with me and Dr. Rohan Garje, who has been my principal investigator for this to help us proceeding over this [inaudible 00:05:24].
Zachary Klaassen: Wonderful. Thank you so much.
Arjun Pon Avudaiappan: Thank you.