Two ASCO Abstracts May Transform Metastatic Castration Resistant Prostate Cancer Treatment in First-Line Setting

At the 2023 ASCO Annual Meeting, there were 2 abstracts that have the potential to change the treatment of metastatic castration resistant prostate cancer (mCRPC) in the first-line setting, explained Veronica Ajewole, PharmD, BCOP, during a panel discussion at the inaugural 2023 PTCE Oncology Pharmacists Connect conference. These abstracts were on the TALAPRO-2 trial (abstract 5053) and PROpel trial (abstract 5012).

The panelists started off the discussion with TALAPRO-2 trial (NCT04821622), which was a double-blind, randomized, placebo-controlled, phase 3 trial assessing talazoparib (Talzenna; Pfizer) in combination with enzalutamide (Xtandi; Astellas) vs placebo in combination with enzalutamide.

Prostate cancer illustration | Image credit: Dr_Microbe - stock.adobe.com

According to panelist Jamie K. Joy, PharmD, community site pharmacy operations manager at Fred Hutchinson Cancer Center in Seattle, Washington, talazoparib in combination with enzalutamide will definitely become a treatment option for this mCRPC patient population.

“This is actually under FDA review right now. Now, the patients were ECOG 1 one or less, so fairly fit patients,” Joy said. “I do think that this could become a standard of care. [However,] I do think the right patient has to be picked, as there were more toxicities in these patients, as we see a lot with the PARP inhibitors, and then also you're adding another pill. So now they're on 2 drugs. So the pill burden and financial considerations, I think those are the things I would think about.”

Rebecca Tombleson, PharmD, BCOP, board certified oncology pharmacist in Tampa, Florida, explained that although she thinks talazoparib plus enzalutamide is definitely an interesting combination, what concerns her is the 90% discontinuation rate.

“So, as mentioned, you really have to make sure you're choosing the correct patient for this regimen. Beyond the adverse event profile, which was pretty concerning in terms of anemia, what I love was it was very transparent, as patients had baseline issues with anemia going into the study. So we knew to expect that,” Tombleson said. “However, we saw really deep issues with anemia and transfusion dependence occurring right around 3 months, and as far out as 6 months, with patients needing transfusions for their support through their anemia.”

Tombleson noted that although she does think the combination therapy is a helpful regimen for the right patient, the concern remains that the transfusion dependence may negate some of the benefits gained from the freedom of an oral regimen due to the need for monitoring.

Ajewole agreed on this point, noting that there is also added cost to needing that additional support around transfusion.

“If we need to have transfusion refractory support, you're looking at additional coordination,” Ajewole said. “Patients on oral oncolytics are not used to coming into the clinic often. So if they do need to get transfusion, there are additional things to consider when it comes to coordination of care.”

Joy added that this patient population is also generally not monitored that long as well. So anemia up to 6 months is pretty long, with patients potentially needing closer monitoring in the beginning of treatment.

“That's just something to be aware of for patients that get put on this [combination therapy],” Joy said. “Then another thing I wanted to point out is the dosing is actually different for this in prostate [cancer] than it is in breast [cancer]. I just wanted to point that out, because we're pharmacists, so the dosing in the study was 0.5 milligrams, and the breast dose is 1 milligram.”

Ajewole noted that this was an important point for practice, as pharmacists may often assume the dose will be 1 milligram for all patients, but in this case, it would be 0.5 milligrams. Based on weight and renal dysfunction, the dose reduction could go to 0.35 milligrams. Of note, most patients in the study that did have a dose reduction modification stayed on 0.4 milligrams.

For the second abstract on the PROpel trial (NCT03729362), Ajewole noted it was particularly interesting that the study data led to the FDA approval of the abiraterone (Zytiga; Janssen Biotech) plus olaparib (Lynparza; AstraZeneca) combination therapy 2 days before the start of the ASCO annual meeting.

Additionally, Joy noted that from a managed care perspective, there's also compendium support for this combination therapy.

“It is for those patients with suspected deleterious or delayed various germline or somatic homologous repair gene mutated [mCRPC]. We're still waiting on guidance, to the best of my knowledge, from NCCN,” Joy said. “I think it's great to also see a quality-of-life study done in this patient population. I loved it, and I think members of the audience loved it as well.”

Beyond measuring quality of life, this newly approved combination therapy also has an impact on medication adherence, compliance outcomes, and duration of treatment, according to Joy.

“So I think all those things are really helpful when you see that the quality of life is maintained between treatment arms,” Joy said. “What I would caution is that, while the endpoints of this study on quality of life didn't pick up a difference in quality of life, there are still other quality of life issues to be considered, namely cost. So there is not an insignificant increase in cost to go on combination therapy with olaparib versus olaparib plus abiraterone. So even though there wasn't a difference in the study arms, I would want to keep that in mind.”

Joy added that the lack of benefit with that quality of life is also further complicated by the commonly reported anemia adverse event as well.

“So those are just things to caution,” Joy said. “There's definitely clear value in that BRCA-mutated patient population, it's just the other patients that we would have to really consider and really make some judgments on who we start on this.”

Ajewole noted that, in this way, it really all boils down to identifying the best patient and who can actually afford the combination therapy.

Additionally, Joy went on to mention that the fact that the study accounted for pain among patients shows how the study had a bit more of a real world and real-life approach than is common.

“On the other hand, it's subjective, so we have to think about that, and how people report that out,” Joy said. “Another thing was that a patient group actually came in on more opiates than the placebo group, which I thought was interesting that that wasn't quite matched [in each arm]. And there were more opioid-naive patients in the treatment group who did start opioids. So I think that just kind of gives another level of information there that I'm not exactly sure what to do with, but I do think it is interesting and contributes to the data.”

Reference

Ajewole V. Therapeutic Developments Transforming the Treatment of Prostate Cancer. Presented at: 2023 PTCE Oncology Pharmacists Connect in Austin, Texas; June 16, 2023.