Atul Batra: Thank you. First of all, I need to thank you for inviting me here. And yeah, it's a pleasure to be with you always.
Neeraj Agarwal: So Atul, tell me about the patient population first, and then what is the dose of carboplatin used, and then we can talk about the results. So, what is the patient population here?
Atul Batra: So, this was metastatic castrate-resistant. We shouldn't be calling that castrate-resistant, we would call it ARPI-resistant kind of prostate cancer with metastasis, who had previously received either docetaxel or an ARPI, or both, so all these were allowed. And they need to have a mutation, either germline or somatic in one of the HRR genes. So this was a 15 gene panel. One we removed from the PROfound one, the PPARA, otherwise BRCA2, one, ATM, CHEK2, RAD51, all those genes. And they need to have progressed on their prior line, fit enough to receive carboplatin. And the dose of carboplatin was AUC5, administered intravenously every three weeks.
Neeraj Agarwal: Okay. So, thank you for correcting me. This is a patient population with metastatic castration-resistant prostate cancer. Now, should preferably be called as androgen pathway modulation-resistant prostate cancer, so APM. I'm glad to be getting rid of the word castration.
Atul Batra: Certainly.
Neeraj Agarwal: Nobody liked it, in my opinion, in my experience. So, let's stick to the castration-resistant word for now, because this is how you use the terminology in the trial. So, these patients had metastatic castrate-resistant prostate cancer with either somatic or germline mutation in the HRR genes, homologous recombination repair pathway genes. And they had to have disease progression on a ARPI and docetaxel.
Atul Batra: And/or. So, they could have received one of them or both of them.
Neeraj Agarwal: Okay. And then you treated these patients with carboplatin with pretty much standard dose every three weeks. So please tell us about the results.
Atul Batra: So this was over two years, this was a single [inaudible 00:03:05] study.
Neeraj Agarwal: And how many patients were there?
Atul Batra: So we screened 213 patients, 213 patients over two years at our center. And there were total 45 patients who tested positive, and 39 ultimately were enrolled in the clinical trial. So, the most common mutation was BRCA2, which was the most common, followed by ATM. And then these patients went on to receive carboplatin. So the primary endpoint here was PSA50 response within six months, and which was in the overall population, this was 41%. And in BRCA2 positive mutated patients, this was 63.7%. So, there were 11 patients who had this mutation and six of them responded with this carboplatin.
Neeraj Agarwal: So out of-
Atul Batra: Seven of them. That's 63.7%, yeah.
Neeraj Agarwal: Yeah. So you screened about 213 patients, but about 40 patients who were positive for germline or somatic mutations in HRR genes. And you saw, if I remember correctly, across the board, 40% PSA 50% response, meaning 40% of these patients achieved a more than 50% or more decline of the baseline PSA. And in BRCA2 patient population, it was 63% PSA 50% response. Those are really encouraging data, especially for those patients who do not have access to PARP inhibitors.
Atul Batra: That's true. That was the population that we were targeting, so these patients also did not have access to PARP inhibitors. It was pretty expensive and it's still not accessible and I mean, across the globe, over large populations in Africa or the Southern America, even in India, the cost is a big barrier. So, carboplatin being often called as a poor-man PARP inhibitor, that's why we wanted to do this trial just to see if we are achieving similar numbers. And this could become potentially an option for patients who do not have access to these PARP inhibitors.
Neeraj Agarwal: Very good point. Any safety signal?
Atul Batra: No, we didn't see. Carboplatin has been used, I mean, through generations and-
Neeraj Agarwal: But I'm talking about any excessive hematologic side effects of carboplatin in patients who have say, germline mutation, which basically means those mutations are also present in the hematopoietic cells.
Atul Batra: No, I didn't see that many. So if you go back to ovarian cancer and breast cancer, I mean, these are also the BRCA mutations are much more common there, and platinum is used in nearly all patients breast and ovarian cancer. So, no such signals have previously been seen and we also didn't see such signals.
Neeraj Agarwal: That's great to know, especially when many of our urology colleagues and medical oncology colleagues out there in the community are contemplating alternative therapy for many of these patients worldwide when they don't have access to PARP inhibitors. The message here is that patients with germline testing or germline mutations or somatic mutations in homologous recombination repair genes, they have these meaningful PSA 50% response with carboplatin in a pre-treatment setting. So, either these patients have received docetaxel or they had received PARP inhibitor, ARPI, and they seem to have a meaningful response, in my view.
Atul Batra: Yeah, absolutely.
Neeraj Agarwal: Any data on radiographic progression-free survival or any other response data?
Atul Batra: So we are looking into that more closely, the radiographic progression-free survival, but we have certain patients who have now received up to 20 cycles of carboplatin-
Neeraj Agarwal: Wow.
Atul Batra: ... and they seem to be in a deep response. And whatever data we saw with PARP inhibitors, like BRCA2, are the ones who are primarily the responsive ones, and ATM response is not that great. So, the ATM response was around 30%, and then rest of the mutations were like one each, so it doesn't make sense to make too much out of that. But BRCA2 seems to be pretty impressive response rate, and some of them going for almost more than a year with carboplatin.
Neeraj Agarwal: That's very encouraging. So again, the message looks like, patients who don't have access to PARP inhibitors and who have castration-resistant prostate cancer, which has progressed on either ARPIs or docetaxel, and who have germline or somatic mutations in HRR genes, based on these data and of course based on data from other cancers, carboplatin may be a reasonable option. Would you agree?
Atul Batra: Absolutely. It is an option for those patients.
Neeraj Agarwal: Atul, thank you so much for first of all, congratulations on leading this very meaningful study, and for showing that one more option is feasible for our patients with metastatic prostate cancer with HRR mutations.
Atul Batra: Thank you so much for having me here. It's a pleasure to be here. Thank you.
Neeraj Agarwal: Thanks.