Kristie L. Kahl

The National Comprehensive Cancer Network (NCCN) has recommended the combination use of lenvatinib (Lenvima) plus pembrolizumab (Keytruda) for the frontline treatment of renal cell carcinoma (RCC).

This recommendation is key for urologists to be aware of, in particular, because of the role of themultidisciplinary approach to cancer care. “The urologist should be aware of these data in particular because of the question of whether cytoreductive nephrectomy is appropriate or not,” Eric Jonasch, MD, professor in the Department of Genitourinary Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas, and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview with 

“Even with less powerful regimens, the role of cytoreductive nephrectomy has decreased , so that for individuals who have intermediate and poor risk disease, in particular, systemic therapy should be the frontline choice for most patients.”

The panel comprised by the organization based its category 1 recommendation on findings from the phase 3 CLEAR trial (NCT02811861), designed to evaluate the combination of lenvatinib with either pembrolizumab or everolimus (Afinitor), compared with sunitinib (Sutent) for the treatment of patients with advanced RCC receiving therapy in the frontline setting.

Patients were randomized in a 1:1:1 fashion to receive either 20 mg oral lenvatinib once daily plus 200 mg IV pembrolizumab once every 3 weeks (n = 355); 18 mg oral lenvatinib once daily plus 5 mg oral everolimus once daily (n = 357); or 50 mg oral sunitinib once daily for 4 weeks on and 2 weeks off (n = 357).

Progression-free survival (PFS) by Independent Review Committee (IRC) per RECIST v1.1 was the primary end point. Secondary end points included overall survival (OS), objective response rate (ORR) by IRC per RECIST v1.1, safety and health-related quality of life (HRQoL).

The median PFS with lenvatinib and pembrolizumab was 23.9 months (95% CI, 20.8-27.7) compared to 9.2 months (95% CI, 6-11) with single-agent sunitinib (HR, 0.39; 95% CI, 0.32-0.49; 

 <.001). The lenvatinib plus everolimus treatment arm achieved a median PFS of 14.7 months (95% CI, 11.1-16.7) compared to the 9.2 months in the sunitinib arm (HR, 0.65; 95% CI, 0.53-0.8; 

A median OS was not reached in any of the three treatment arms; however, the data indicated the end point was significantly longer in the lenvatinib and pembrolizumab arm compared to the sunitinib arm (HR, 0.66; 95% CI, 0.49-0.88; 

ORR was higher in both the lenvatinib plus pembrolizumab (71%; 95% CI, 66.3-75.7) and lenvatinib plus everolimus (53.5%; 95% CI, 48.3-58.7) treatment arms compared to sunitinib (36.1%; 95% CI, 31.2-41.1). In particular, Jonasch noted that the 16% CR rate with lenvatinib plus pembrolizumab was impressive.

Lastly, patients in the lenvatinib plus pembrolizumab arm achieved the longest median DOR at 25.8 months (95% CI, 22.1-27.9), compared to 16.6 months (95% CI, 14.6-20.6) in the lenvatinib plus everolimus arm and 14.6 months (95% CI, 9.4-16.7) in the sunitinib arm.

“This trial basically showed various, very strong results in all of these domains. … All of these factors, together, show that this is one of the strongest regimens that's been tested so far in advanced kidney cancer,” Jonasch explained. “And so the NCCN panel felt that these data deserve preferred status.”

Although systemic therapy is recommended, Jonasch continued that there could still be the integration of therapy – highlighting the need for a multidisciplinary approach. “[With this recommendation], the integration of surgery and systemic therapy becomes even more important,” he said. “The timing of one versus the other is also important for the patient’s well-being, especially when you can get such rapid response with systemic therapy. But it doesn't, in any way, diminish the role of the surgeon in the team. The team consists of the medical oncologist, the surgeon, the radiation oncologist and the nursing staff, as it has before.”

Moreover, this recommendation highlights the need for open patient-physician communication. “…the patient or therapy-related details a skilled oncologist evaluates to make these decisions can prioritize those therapies, even within the preferred category. Or there might be some circumstances that will make a preferred regimen not appropriate for a particular patient,” he explained. “So, this is obviously a conversation that needs to occur between the patient and the physician. The physician can then explain what the different regimens are in these various categories, explain why one would be chosen over the other and whether there may be other choices that are not preferred, but that might actually be ideal for that particular patient for various reasons.”

1. National Comprehensive Cancer Network. Kidney Cancer. Version 3.2021. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf.

2. Motzer RJ, Alekseev B, Rha S.-Y., et al. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. Published online February 13, 2021. 

Articles

This recommendation is key for urologists to be aware of, in particular, because of the role of the multidisciplinary approach to renal cell carcinoma care, according to Eric Jonasch, MD.

NCCN adds frontline lenvatinib/pembrolizumab to Category 1 recommendation for advanced RCC

 Interdisciplinary Prostate Cancer Congress® and Other Genitourinary Malignancies, Phillip J. Koo, MD, highlighted the potential of next-generation imaging to revolutionize the management of patients with prostate cancer.

Koo, chief of Diagnostic Imaging, Northwest Region Oncology Physician Executive, Banner MD Anderson Cancer Center, Phoenix, Arizona, discussed the emergence of next-generation imaging; novel imaging agents, such as those targeting PSMA; and how these novel imaging techniques are “here to stay” in the prostate cancer paradigm.

While conventional imaging techniques—such as bone scans, CT, or MRI—date back to the 1970s, their use does have limitations. For example, Koo noted that although bone scans are widely available and can help to identify bone lesions, they rarely identify asymptomatic disease or positively identify disease with the absence of a high PSA. Similarly, while CT scans can follow treatment response and can detect metastases, they cannot detect recurrent tumors and are dependent on size for nodal evaluation, which can result in poor sensitivity.

Therefore, this is why there has been a shift in focus toward next-generation imaging. In particular, this strategy may allow clinicians to see things that they wouldn’t be able to see using conventional imaging.

“It’s almost like the difference between a high-definition TV versus your standard TV,” Koo explained. “And we all recognize [that] with high-def, it’s just amazing what more you can see and how better appreciated that becomes.”

Moreover, he added, several specialized imaging techniques have emerged that may permit the acquisition of digital images at high resolution, which may have diagnostic potential to introduce new opportunities to more accurately assess disease burden. However, there is a lack of standardization or practical application of next-generation imaging in prostate cancer.

Next-generation imaging works by taking advantage of the unique biological aspects of prostate cancer carcinogens. Molecular imaging probes, of which several are already in clinical use or under evaluation, can be divided into images with increased cell metabolism, those that target prostate cancer–specific membrane proteins and receptor molecules, and those that bind to the bone matrix adjacent to metastases to the bone. Therefore, increased metabolism and vascular changes in prostate cancer cells can be evaluated with radiolabled analogs of choline, acetate, glucose, amino acids, and nucleotides, Koo explained.

One example Koo provided of next-generation imaging was 18F-fluciclovine. Approved by the FDA in 2016, 18F-fluciclovine is a synthetic amino acid PET imaging agent that has demonstrated the ability to recognize amino acid transporters, which have been shown to be upregulated in many cancer cells, he explained. Additionally, because the radiotracer was not metabolized or incorporated into newly synthesized proteins, it may not interfere with normal protein synthesis.

“When the data were first reported in patients with biochemical recurrence with a PSA level of less than or equal to 0.79, it actually had a detection rate of 41% which is pretty remarkable given that lower PSA level. That’s why it created a lot of excitement, that we could image disease better at biochemical recurrence,” Koo said.

Next, clinicians have moved into the evaluation of PSMA PET technology. PSMA is a membrane protein that has been shown to have a significant overexpression in prostatic tissue but low expression in normal tissue. Koo explained that high image quality could be achieved with PSMA PET because of the uptake in ligand bonding PSMA into the prostate cancer tumor cells. PSMA PET agents that are currently under investigation include 68Ga PSMA and 18F-DCFPyL PSMA; however, of note, neither imaging agent is FDA approved yet.

Next-generation imaging versus conventional imaging

In a prospective, single-center, open-label, single-arm comparative study, Michael S. Hoffman, MD, and colleagues compared 18F-fluciclovine and PSMA PET-CT scans for localizing biochemical recurrence of prostate cancer after radical prostatectomy in patients with low PSA concentrations (<2.0 ng/mL).

The investigators found that, among the 50 participants, detection rates were significantly lower with 18F-fluciclovine PET-CT (n = 13 [26%]; 95% CI, 15%-40%) than with PSMA PET-CT (n = 28 [56%]; 95% CI, 41%-70%), with an odds ratio (OR) of 4.8 (95% CI, 1.6-19.2; 

 = .0026) at the patient level. They concluded that PSMA should be the PET tracer of choice when PET-CT imaging is considered for subsequent treatment management decisions in patients with prostate cancer and biochemical recurrence after radical prostatectomy and low PSA concentrations.

“The accuracy was much better than conventional imaging, [which was] not surprising, and they had a greater treatment impact,” Koo said. “It also had fewer uncertain results. So that’s something that I think is very important: An imaging test having less equivocal results is more powerful…hopefully this can get rid of that hedge in the future for radiology and nuclear medicine.”

Translating next-generation imaging into practice

With all of these data, Koo highlighted that it led to a “monumental day” in December 2020: The FDA approved the first PSMA-targeted PET imaging drug for men with prostate cancer.

“[The approval] actually had 2 indications. Number 1, it had the indications for use in patients with biochemical recurrence, which is something that we were used to. But the biggest difference for this approval was it was actually approved for patients at initial diagnosis,” Koo noted. “So it says that it’s indicated for suspected prostate cancer metastases, which are potentially curable by surgery or radiation therapy. This was pre-definitive treatment, which was something new for these next-generation imaging agents.”

Before concluding, Koo did note that next-generation imaging does no replace pathology: “PET CT can’t detect that microscopic level of detail disease in these patients, so we need to sort of separate the 2, because I often see that being assumed when it comes to pet imaging.”

However, Koo added, next generation imaging is here to stay. “For those of you in the audience who are resistant, I recommend that you start getting a bit more and more comfortable each year because it’s not going anywhere.”

1. Koo PJ. Next Generation Imaging in Prostate Cancer. Presented at: 14th Annual New York GU Congress; March 12-13, 2021.

2. Bach-Gansmo T, Nanni C, Nieh PT, et al. Multisite Experience of the Safety, Detection Rate and Diagnostic Performance of Fluciclovine (18 F) Positron Emission Tomography/Computerized Tomography Imaging in the Staging of Biochemically Recurrent Prostate Cancer. 

. 2017;197(3 Pt 1):676-638. doi:10.1016/j.juro.2016.09.117.

3. Calais J, Ceci F, Eiber M, et al. 8F-fluciclovine PET-CT and 68Ga-PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single-centre, single-arm, comparative imaging trial. 

. 2019;20(9):1286-1294. doi: 10.1016/S1470-2045(19)30415-2

At the New York GU 14th Annual Interdisciplinary Prostate Cancer Congress® and Other Genitourinary Malignancies, Phillip J. Koo, MD, highlighted the potential of next-generation imaging to revolutionize the management of patients with prostate cancer.

Next-generation imaging marks dawn of new era in prostate cancer paradigm

Imaging with 18F-DCFPyL, a novel prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical for positron emission tomography (PET), may identify occult prostate cancer and more accurately characterized disease burden, according to a subanalysis of the OSPREY trial presented at the 2021 Genitourinary Cancers Symposium.

“18F-DCFPyL-PET/CT identified M1 disease in the majority of patients examined who otherwise had locoregional disease,” the researchers wrote. “These data suggest that 18F-DCFPyL-PET/CT may be a useful tool in properly staging men with both metastatic and nonmetastatic relapsed disease, which could lead to superior treatment paradigms than currently exist using conventional imaging.”

In the poster presentation, Jeremy C. Durack, MD, MS, interventional radiologist, Memorial Sloan Kettering Cancer Center, noted that previous topline results demonstrated the following:

18F-DCFPyL helped to identify recurrent/metastatic prostate cancer, with a positive predictive value (PPV) of 82% and sensitivity of 96%.

18F-DCFPyL demonstrated a 40% sensitivity rate, compared to 40% with conventional imaging, as well as a high PPC (87%), an 83% net present value, and 98% specificity in men at high risk for metastatic prostate cancer.

18F-DCFPyL facilitated initial therapy for patients.

In the prospective phase 2/3 study OSPREY study (NCT02981368), conducted across 10 sites in the US and Canada, Durack and colleagues evaluated 18F-DCFPyL in 385 patients broken into 2 cohorts: cohort A (men with high-risk prostate cancer per National Comprehensive Cancer Network guidelines) and cohort B (men with presumptive recurrent or metastatic prostate cancer based on radiologic findings).

The bolus intravenous injection of 18F-DCFPyL was administered at 9 mCI (333 MBq), with imaging beginning 1 to 2 hours after administration.

18F-DCFPyL detection rates were systematically analyzed. The prospective analysis included 3 blinded, independent 18F-DCFPyL-PET/CT readers and 1 blinded conventional imaging reader.

In their poster presentation, the researchers reported on cohort B, in which 18F-DCFPyL-PET/CT was evaluated in 117 men with radiologic evidence of local recurrence or metastatic disease on baseline anatomical imaging, including a CT scan or MRI, or whole-body bone scintigraphy and in whom at least 1 lesion was deemed amenable to biopsy.

Key efficacy end points from cohort B included sensitivity of 18F-DCFPyL imaging within metastatic lesions relative to histopathology, positive predictive value (PPV) within metastatic lesions, and detection rates between 18F-DCFPyL and conventional imaging.

At baseline, 82 patients (71%) had radiographic M1 stage disease, including 14 patients with M1a, 50 patients with M1b, 18 patients with M1c; 33 patients (29%) were M0 stage at baseline by central conventional imaging review; and 2 patients were unevaluable. In addition, 28% (n = 32) had PSA <2.0 ng/mL.

Of the 33 patients with M0 stage using conventional imaging, 18F-DCFPyL up-staged 19 (58%) men to M1 stage. Ten (91%) of 11 men underwent an extra-pelvic biopsy and were confirmed to have M1 disease by pathology, including 9 patients with M1b and 1 patient with M1a.

Of the 82 patients with M1 stage at baseline using conventional imaging, 18F-DCFPyL up-staged 10 men (12%) to a higher M1 sub-stage, including 4 patients from M1a to M1b or M1c and 6 patients from M1b to M1c. Moreover, 18F-DCFPyL down-staged 18 men (22%) to M0 in this group.

“Conventional imaging and bone scintigraphy are suboptimal modalities for identifying (prostate cancer),” the researchers wrote. “PSMA-based imaging is highly promising for (prostate cancer) detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for PET that may be useful in staging of (prostate cancer).”

1. Durack JC, Alva AS, Preston MA, et al. A prospective phase II/III study of PSMA-targeted 18F-DCFPyL-PET/CT in patients (pts) with prostate cancer (PCa) (OSPREY): A subanalysis of disease staging changes in PCa pts with recurrence or metastases on conventional imaging. Presented at: 2021 Genitourinary Cancers Symposium; February 11-13, 2021; Virtual. Abstract 32.

The novel PSMA-targeted radiopharmaceutical for PET identified M1 disease in the majority of patients examined who otherwise had locoregional disease, according to a subanalysis of the OSPREY trial.

18F-DCFPyL may aid in staging men with metastatic, nonmetastatic relapsed prostate cancer

Dr. Concepcion, can you talk about some of these new therapies that were approved in 2020?

 There has been a lot of advancement in the whole management and approval of agents in advanced prostate cancer, let's just start there. And I think it's important for our viewing audience. When we talk about prostate cancer, whether it's localized or whether it's advanced, I think we need to be very specific on the type of patient that we're discussing. Because again, I think that the therapies, whether it's in surgery, radiation, active surveillance in the localized space, or whether it's in the advanced space, all the trials, all the therapies, all the indications depend upon the particular phenotype we're discussing.

For localized prostate cancer, I think we need to be discussing patients as they fall into NCCN risk stratification. So, they're either very low risk, low risk, favorable intermediate, unfavorable intermediate, high risk, and very high risk. Depending upon the risk stratification, we will determine what options are available to you. And as we know, in the localized prostate cancer space, especially very low risk and low risk, we should be utilizing and talking to our patients about active surveillance, which is not appropriate in the unfavorable intermediate or high-risk patients. So that's why we need to be very specific when talking about low risk or local prostate cancer, or the advanced prostate cancer space, which I define as anybody that you're thinking about starting androgen deprivation therapy.

Historically, in the metastatic castration resistant prostate cancer space, which used to be known as M1, we've pushed back a little bit to this arbitrary designation of M0 or nonmetastatic castration resistant prostate cancer. Over the past five years, there has been a market change in the paradigm and the therapeutics in the metastatic castration-sensitive prostate cancer space. But we have patients in the nonmetastatic castration-sensitive prostate cancer space, which historically has the biochemical failures. When we focus specifically on castration-resistant prostate cancer, most of the last decade, we saw a slew of agents that were approved, whether they be androgen receptor targeting agents, or synthesis inhibitors as receptors or receptor antagonists; autologous immunotherapy; alpha emitting radiopharmaceuticals; and taxane therapies. Once (those therapies were) flushed out, we really didn't see a whole lot. but over the past couple of years, we've seen all those agents now get approved in a much earlier phenotype. So initially, all of those mechanistically different agents were approved in metastatic castration-resistant prostate cancer. Now, some of those agents have been approved in the nonmetastatic castration-resistant prostate cancer. That entire nonmetastatic castration-resistant prostate cancer space may completely go away as we utilize molecular imaging. So, we've seen a push towards some of these agents earlier in the disease, primarily the nonmetastatic castration-resistant prostate cancer space. And that's been over the past couple years. We've seen therapeutic regimens change for the metastatic castration-sensitive prostate cancer space, that's either patients that present with de novo metastatic disease, or patients that progress beyond definitive therapy. But it's only been this past year where we've had finally a newer mechanistically different newer agent that finally has been approved for metastatic castration resistant prostate cancer.

 I think that this whole thing is about precision guided therapy. Having been in practice now, for the better part of 20 years, I've seen the era of giving everybody some sort of hormonal agent and probably a lot of it was used inappropriately. I think that the paradigm is shifting to (doing somatic tumor testing). We're going to look at the biology of the tumor, we're going to look for whether or not you have hereditary cancer inheritance, and we might have a lock in a key for your disease. So that lock and key has come about with things that are called PARP inhibitors.

We now know that patients have some sort of deleterious DNA repair gene abnormality, and that's a basket of multiple genes. The one that has the biggest claim to fame are 

. Those patients have been shown, without any doubt, that usage of these PARP inhibitor therapies, specifically olaparib (Lynparza) and rucaparib (Rubraca), are of benefit in that disease space. So, they're a little bit different in a labeling indication, the labeling indication for Lynparza is pretty broad based. And that is inclusive of anyone who has catrate-resistant prostate cancer and has failed some sort of novel hormonal agent. If those patients have some sort of deleterious mutation, it's really a pretty provocative improvement in overall survival. What needs to be worked out is which genes have the best survival? As you look at that gene pool, is the 

 mutation? We're beginning to understand that, but it's another tool we have in our toolbox.

Another tool that we have in our armamentarium is the possibility of checkpoint inhibitor therapy. Checkpoint inhibitors are immune stimulating agents, for lack of a better term. There's a lot of buzz on that in the urology world. We have a potential indication that's really based on patients who have precision-guided therapy. You're going to look at their tumor mechanism, see if they have some sort of mismatch repair, see if the patients have a high tumor mutational burden. As we start to embrace these checkpoint inhibitors, it’s very exciting times in terms of these new approvals for these new drugs. And just like anything in life, once you get approval, then the pharma companies drive that approval earlier and earlier in the disease.

Chris, I think you make some really great points. The big point is when you start looking at PARP inhibition, and it is critical that in order to really understand how this drug works, you have to understand DNA damage repair. So basically, all of these pathogenic variants and mutations really are happening in DNA damage repair genes, which is sort of a broad category. When you have DNA damage repair genes, you really have 2 different types of pathways. You have homologous recombination, which is 

 checkpoints; and you have the DNA mismatch repairs, which are single stranded breaks in a number of genes, including 

. You also have to look at microsatellite instability. And it's important to understand the difference of what makes a tumor MSI-high. Now all of a sudden, you have neoantigens that get manufactured by these tumor cells, which makes them more immunogenic. So to Chris's point, the concept, especially as we move further and further along down this progression of heavily treated CRPC patients…what we as urologist need to start looking at is obviously an understanding of the molecular drivers and understanding of the DNA damage repair pathways, but more importantly, what testing should we be ordering when the patient progresses? Should is be somatic or germline?

Our understanding of potential germline mutations is now relevant in prostate cancer, and I'll let Chris address the newer approval this year, as it went along with the approval of PARP inhibitors, is this concept of liquid biopsy. But you also have some other tests out there, which are androgen receptor variants – the AR-V7 assay, which is a circulating tumor cell assay. Once a patient starts to progress, you need to be thinking of a whole battery of tests that will include or preclude what your next line of therapy is, not just focusing on 1 particular therapy, because then you're going to potentially lose out on some other therapeutics that the patient may benefit from.

 I completely agree. I think that the era of managing hormonal manipulation to treat the cancer is going to be just 1 chapter in the life story of this prostate cancer patient. I think hat a lot of urologist are comfortable with injectable therapy, but few are comfortable with oral, antihormonal therapy and even fewer are going to be comfortable with these real chemotherapies. For a lot of us that are passionate about this, we want to help our colleagues be educated about retaining these patients. And the reason why, quite honestly, is that we're converting this disease from what was uniformly fatal a couple of years ago into something that becomes more chronic.

These patients who are failing on novel hormonal therapy are still pretty healthy, and they still want to see their urologist. Part of that is becoming comfortable with these newer drug indications. Pandora's box is going to be open with all these additional precision therapies that are available for other disease states. It's a really kind of exciting time for us. And I think our job as the clinician-scientist is to be able to communicate that to our physician urology colleagues in a way that they can understand and be able to use these drugs. Because if you're not doing the molecular testing, if you're not looking under the covers, you're going to miss the potential benefit for the patient. You have to be following the guidelines for these genetic tests. And these are all new in the NCCN. If you have a patient who has high risk disease, you might consider doing some of these hereditary tests.

According to the NCCN guidelines, patients with metastasis ought to have somatic tumor testing done. So that's just a complete paradigm shift for us. And it's been made a little bit easier, because we have the availability of looking at circulating tumor cells rather than biopsies for that. It's a pretty intriguing time for us. I think once the real world comes back post-COVID, and we have the ability to get together in rooms, educate ourselves, that in the next year, hopefully, this is going to be really hot topic.

 Chris, I think you make a really excellent point. At the last live meeting I went to, my friend Dave Patterson, who's the chairman of urology at Vanderbilt talked about toxicity in the face of therapeutic side effects. The point that you made earlier is that many patients, even though they've blown through 2 or 3 lines of therapy, many of these patients still maintain a great quality of life and they want to maintain that quality of life.

There is also financial toxicity. For example, CAR T-cell therapies could be approaching $1 million dollars. This is kind of unsustainable, so we need to think of toxicity, not just as what the drug does to the patient, but the maintenance of quality of life for these patients as well as the financial toxicity. And again, as some of these agents get older, we know that there are some other potential more suitable, maybe even potentially more patient-friendly agents out there that we could be utilizing, especially in the in the area of androgen receptor targeting agents.

 The hot button topic with thesee expensive and Part D drugs are patients feel the heat on that because, again, it's not billed directly to Medicare, like the injectables are. In the last couple of years, we've seen 1 of the drugs go off-patent. So the drug called Zytiga, which is the traditional form of medicine called abiraterone, the generic went off patent. And there's a generic availability now. And, you know, I think for a lot of us, we thought, well, this is going to be great, it's going to be easily accessible, we're going to be able to get it easier, it's going to be dirt cheap, and that's really far from the truth.

In the real world, using the generic means a couple things. One, there's effectively no payment assistance; there's no sort of pharma backing on that because it's generic. There's no educational support of any sort. At least in my practice, I rely heavily on my industry partners to provide me information to then provide to patients, like getting a website and looking at it. Using those resources makes my job easier.

There is a formulation of abiraterone that is micropolymerized, called Yonsa, and it was really manufactured to try to harness the benefit of trying to take abiraterone, which we know has benefit in CRPC patients in a way that's easier for the patients. Getting back to complains, there’s the financial aspect and also the aspect that it is easier for the patient to take. So when you take generic abiraterone, quite honestly, it's a pain. It's difficult because you have to take it on an empty stomach. And, you know, for a lot of patients, there's pill issues. They take all their pills in the morning with breakfast, and then you've got another sort of additional set of pills that need to be taken on an empty stomach. And really the advent of this drug is that is was formulated in such a way that it can be taken with or without food. From a compliance standpoint, at least in my practice, I've found that to be much easier, and I've really leveraged my relationship with the manufacturer to try and get patient assistance. So when a patient has a generic, there's no one out there to help them besides my own staff. So I want to be able to if I decide a patient has to go on a drug, to give it to them without having to fight a ton of fights on that. Raoul, what are your thoughts on this micronized version of abiraterone?

 Yonsa was quietly approved. We’ve been looking at this drug for a couple of years, and there are clearly some inherent advantages of this micronized formulation. Chris, you bring out a great point that when the original abiraterone acetate went generic and these generic companies were lining up, 1 thing that patients depend upon or practice depends upon is pharmaceutical manufacturer support. It's important to understand that Yonsa not a generic drug, it is a branded drug. And so Sun Pharmaceuticals can actually give your practice support very similar to any other branded drug that we're using.

When you look at the data, relative to areas under the curve bioavailability, because of this micronized formulation, which allows for better absorption and, therefore, better levels within the bloodstream, they're able to use a lower dose, which potentially has its benefits. With Yonsa, there is a lower dose; you don't have to worry about food and the variability with or without food; and the plasma concentration is relatively stable.

When you look at the androgen receptor antagonists, it's sort of the same story. We have enzalutamide (Xtandi) and apalutamide (Erleada), which are receptor antagonists, but we also know that there is a significant fatigue factor and potentially a seizure risk with those 2 agents. Now, a little bit mechanistically different but still a novel hormonal therapy is darolutamide (Nubeqa), which we believe, has less of a fatigue factor. So as we take into account the quality of life issue, these things all have to be taken into consideration when talking to a patient

To your point, Chris, which is why I think that people have moved these oral agents up into the whole cascade, is people would rather take an oral pill as opposed to an injection. That's why it's going to have its advantages as an LHRH antagonists, because it's a pill. But I think it's important for the audience, if you're going to treat advanced prostate cancer, you can't pick and choose which 1 of these agents you're going to deliver. You have to be willing to give all agents whether it's pills, injections, radiopharmaceuticals, because they all will be part of the potential therapeutics out there as these patients progress and develop resistance mechanisms.

Kristie L. Kahl

Articles

NCCN adds frontline lenvatinib/pembrolizumab to Category 1 recommendation for advanced RCC

Next-generation imaging marks dawn of new era in prostate cancer paradigm

18F-DCFPyL may aid in staging men with metastatic, nonmetastatic relapsed prostate cancer

PARP Inhibitors and Immunotherapy in Prostate Cancer