177Lu-PSMA Appears Feasible Following Ra-223 in Metastatic Castration-Resistant Prostate Cancer

A. Oliver Sartor, MD

In a previous phase 3 study, radium-223 (Ra-223) demonstrated an encouraging overall survival benefit and favorable toxicity profile as treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). New reviewed data from patients who received 177Lu-PSMA following treatment with Ra-223 showed that subsequent 177Lu-PSMA was a feasible option for these patients, according an analysis presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program

The global, prospective, observational REASSURE study (NCT02141438) followed patients with mCRPC who received Ra-223 for over 7 years. Data were collected from this analysis to investigate the safety and outcomes of patients with mCRPC who received subsequent 177Lu-PSMA following Ra-223 treatment.

Out of 1465 patients, 26 had received subsequent 177Lu-PSMA following Ra-223. Thirteen patients (50%) had received Ra-223 in combination with another therapy in the second-line setting. Ra-223 was given in a median of 6 doses. Following the end of treatment, 3 patients (12%) had drug-related serious adverse events, and 9 (35%) had grade 3/4 bone marrow suppression-relevant hematologic adverse events.

The median duration of 177Lu-PSMA treatment was 3.5 months, and 19 patients (73%) had received this therapy in the fourth-line setting or later. The median overall survival was 28 months from the beginning of Ra-223 treatment compared with 13.2 months from the start of 177Lu-PSMA.

In an interview with Targeted Oncology, A. Oliver Sartor, MD, professor of Medicine, medical director of Tulane Cancer Center, and C. E. and Bernadine Laborde Professor of Cancer Research at Tulane University, discussed the findings for subsequent 177Lu-PSMA following Ra-223 as treatment of patients with mCRPC, as well as the next steps for this research.

TARGETED ONCOLOGY: What was the rationale for evaluating this particular regimen?

Sartor: The beta emitters have been approved for some period of time in prostate cancer, but those beta emitters that are approved include things like samarium-153 and strontium-89. More recently, there are new beta emitters around which there's some excitement. In particular, these are the BCMA-targeted 177Lu-PSMA products, and there was a randomized phase 2 showing some positive results at ASCO. There's a large phase 3 that is fully accrued called the VISION trial, and, as it turns out, almost all the PSMA 177Lu-PSMA trials have excluded prior radiopharmaceuticals, so there's virtually no data. It turns out that the alpha betta Ra-223 has been in use an FDA-approved treatment for some years now. What we did was try to understand how these 2 may interrelate and if there were safety signals that would come through. We really couldn't have a lot of efficacy signals given the limited trial design issues that we were faced with, but nevertheless, we wanted to know, were there any issues that might arise if these agents for used sequentially?

TARGETED ONCOLOGY: What were the methods of design for this, and what did the patient population look like here?

Sartor: The group that has been involved with Ra-223, which includes a fair number of us, had been charged with looking at longer-term follow-up for the Ra-223-treated patients. It turns out we have a pretty extensive database that we can draw upon for understanding what the ultimate outcomes might be for these particular Ra-223-treated patients in selected centers that are involved with the so-called REASSURE registry. In addition to outcomes such as leukemia, secondary cancer, and survival, we also collected data with regards to subsequent therapies that we don't understand if the subsequent therapies were effective or not. However, we can understand whether or not they were used and how long they were used, so we can get some durations. That’s really the substrate for the study. People who have been treated with Ra-223 in a selected series of practices, all participating in a prospective registry, and all reporting on subsequent years of 177Lu-PSMA in their patients.

TARGETED ONCOLOGY: What were the results that we saw at ASCO this year?

Sartor: What we understood from the study of this registry is that a series of patients actually did receive sequential radiopharmaceuticals, alpha and beta particles given in sequence. This is important because there's no prior data, and we're not able to discern if there was activity more or less. However, we did not pick up any safety signals.

In this context of safety, we believe that even though it's not a particularly exciting result, these are important results that seem to indicate that these 2 agents can be used sequentially without undue harm. Now, we know that this will take prospective trials in order to properly vet out who might or might not benefit and if there are any toxicities that we did not recognize, so we understand this is very preliminary. It is a baby step, but it's a first step, and that's why it's important.

TARGETED ONCOLOGY: This research is still early, but what are the plans moving forward with this research?

Sartor: There are 2 elements. The first is we're going to continue to expand on the REASSURE registry to continue to examine the patients as they're treated. We've also reached out to individual investigators involved in the study, and of these individual investigators, we are requesting additional information about the safety and efficacy, so we can have more data than what was reported back in the registry. Should we achieve this goal, we'll have a little more insight of the sequential use to these radiopharmaceuticals.

TARGETED ONCOLOGY: What do you hope that oncologists take away from these findings?

Sartor: I think the take-home message right now is that the radiopharmaceuticals are a new and exciting field, and we're just beginning to explore how they might best be utilized in prostate cancer. As we move forward, there is much to learn, not only in the prospective trials that have been designed but also the smaller studies regarding sequential use in turn will help inform clinicians about treatment choices, particularly after the FDA approves 177Lu-PSMA.

_Reference

_{Sartor AO, la Fougere C, Essler M, et al. Disease characteristics and outcome of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who received a beta emitter (177Lu-PSMA) after an alpha emitter (radium-223). J Clin Oncol. 38: 2020 (suppl; abstr e17592). doi: 10.1200/JCO.2020.38.15_suppl.e17592}