Erica DiNapoli

The combination of atezolizumab (Tecentriq) and radium-223 dichloride (Xofigo) did not demonstrate a clinical benefit in patients with metastatic castration-resistant prostate cancer (mCRPC), according to results a phase 1b study that were presented at the 2020 ASCO Virtual Scientific Program.

In the trial, investigators sought to evaluate the safety and tolerability of atezolizumab plus radium-223 in patients with mCRPC, who also had bone metastasis, visceral metastasis and/or lymphadenopathy, and progressed after androgen receptor (AR) inhibitors.

In the analysis, data was collected from 45 enrolled patients with mCRPC as of October 4, 2019. In the initial cohort phase, a concurrent dosing schedule (CDS) was evaluated, in which atezolizumab and radium-223 dichloride were administered on the same day. Following this, patients with mCRPC were randomized 1:1:1 to CDS or 1 of 2 staggered dosing schedules, the latter of which atezolizumab or radium-223 dichloride was introduced a full cycle before the other agent. Patients received 840 mg of atezolizumab intravenously every 2 weeks and 55 kBq/kg of radium-223 intravenously 6 times, for 4 weeks or until unacceptable toxicity or loss of clinical benefit.

Grade 3/4 adverse events (AEs) related to atezolizumab and radium-223 occurred in 34% and 27% of patients, respectively Two patients (5%) had grade 5 AEs related to atezolizumab. At a median follow-up of 13.9 months, the confirmed objective response rate (ORR) was 6.8%, the median relapse progression-free survival (rPFS) was 3 months, and the median overall survival (OS) was 16.3 months.

“The important take-home message of the trial is that we saw a fair amount of immunotherapy-related adverse effects, some of which were significant,” said lead study author Michael J. Morris, MD. “There were two grade 5 adverse effects that we did feel were related to atezolizumab. These were typical side effects such autoimmune hepatitis, autoimmune myositis, and other autoimmune activity.”

, Morris, medical oncologist, clinical director, Genitourinary Medical Oncology Service, and Prostate Cancer Section Head, Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center, discussed the phase 1b results of atezolizumab plus radium-223 in patients with mCRPC.

: Could you elaborate on the rationale of this trial? What prior data suggest that this could be a synergistic combination?

 Radium-223 is an FDA-approved radiopharmaceutical agent that was approved on the basis of prolonging survival in men with bone-dominant metastatic prostate cancer. Preclinical data suggest that, within the area of radium deposition in the bone microenvironment, there is an immune response that may account for at least a portion of its mechanism of action in terms of patient clinical benefit. The reason why we looked at the addition of a PD-L1 antibody, such as atezolizumab, was to leverage that immune effect. We wanted to amplify the immune response and not just on a local level; we wanted to confirm more systemic benefits in patients.

Atezolizumab was given at 840 mg every 2 weeks, until either toxicity or lack of clinical benefit and radium-223 dichloride was given at its FDA-approved dose of 55 kBq/kg every 4 weeks for a maximum of 6 doses. The patient population in the trial comprised men with metastatic prostate cancer. One additional requirement is that men had to have measurable disease so that you could at least see a radiographic effect in either node, which ordinarily you could not see if it was strictly a bone-based disease.

There were essentially 3 different treatment arms that we explored. One was concurrent dosing of radium-223, another was staggered dosing with radium-223 preceding atezolizumab

 and the third was staggering dosing with atezolizumab first followed by radium-223. The primary end point of the trial was safety and tolerability, because this was a phase 1b study. Also, because it did have 3 arms, there was an examination [on the] anticancer affects. Additionally, there were correlative studies looking at approximately 3 pre- and posttreatment biopsies to explore immune effects.

[Aside from the adverse effects], in terms of a countervailing clinical benefit, we did not see anything that we didn’t expect to see with either radium-223 or atezolizumab independently. Radium-223 doesn't independently significantly decline prostate-specific antigen levels, and we didn't see any improvement on that with the addition of atezolizumab. There were 3 patients who had significant and durable radiographic responses: one lasted 192 days, another for 275 days, and the third for 337 days.

However, this was within a total patient population of 44 patients. We didn't believe that we could identify who those patients were [that responded], which has frequently been a problem in terms of immunotherapy and prostate cancer. We felt that the toxicity to clinical benefit ratio did not warrant pushing [the combination] forward.

This is a field that still needs to be actively explored. I do think though that, with immunotherapy drugs, we need to have some sense of how we’re going to mitigate the safety signal in terms of immunotherapy-related toxicity.

What are your theories to the lack of benefit observed with the combination treatment in this patient population? Do you have any theories?

The delivery of the radiation here is not necessarily in the same place as the delivery of the immune effects. Radium-223 delivers therapy with a relatively narrow depth of penetration to the bony compartment itself. Now, how much of that impacts the surrounding tumor bed is unclear. The bone microenvironment is a complex place, but it could also be that we’re not maximizing the interaction between these 2 therapies by delivering a bone-seeking radiopharmaceutical opposed to the immunotherapy.

That’s why we're looking forward to seeing the results of tumor-directed radiation therapy, where we’re actually delivering both treatment modalities in an overlapping area of the bone microenvironment.

Morris MJ, Fong L, Petrylak DP, et al. Safety and clinical activity of atezolizumab + radium-223 dichloride in 2L metastatic castration-resistant prostate cancer: results from a phase Ib clinical trial. 

 2020;38(suppl 15):5565. doi: 10.1200/JCO.2020.38.15_suppl.5565

Articles

Michael J. Morris, MD, discusses the combination of atezolizumab and radium-223 dichloride, which did not demonstrate a clinical benefit in patients with metastatic castration-resistant prostate cancer.

Atezolizumab/Radium-223 Combo Shows No Benefit in mCRPC, But Biomarker Work Planned

The implementation of systematic germline genetic testing in veterans with metastatic prostate cancer appeared to be feasible due to high consent rates, especially with direct oncologist involvement, according to results from a prospective trial. Additionally, data showed that the frequency of germline DNA damage-repair (DDR) alterations is similar to those with prostate cancer who are not veterans.

In the pilot study, investigators studied the feasibility of a systematic workflow that helped oncologists identify veterans with metastatic prostate cancer at VA Puget Sound Health Care System, which cares for veterans who require ongoing cancer therapy. After the patients were prescreened and identified by a research coordinator, an oncologist would discuss germline testing in great detail with both the patients and their families.

A total of 227 patients were approached in this trial. Out of these patients, 84% (n = 182) consented to genetic testing and 90% completed it. Results showed that 7% (n = 12) had a gDDR mutation: 

“The main idea of the study was to identify patients systemically and have oncologists provide germline testing, without creating an extra infrastructure for genetic counseling. Genetic counseling is a different subunit, so patients don’t typically utilize the service,” said lead study author Alexandra Sokolova, MD. “Nowadays, germline testing is important for both patients and their family members because it can help with both the treatment process and the prognosis.”

 Sokolova, a hematology-oncology fellow at Seattle Cancer Care Alliance, discusses the importance of germline testing in patients with metastatic prostate cancer, and the feasibility data observed through a systematic testing model.

: Could you discuss the rationale of this study?

 In 2017, the National Comprehensive Cancer Network (NCCN) recommended germline testing for all men with metastatic prostate cancer. In 2019, this was updated to include all men with high-risk, localized prostate cancer or those [with a family history]. Since prostate cancer is the second most common cancer for men in the United States, this created a strong need to provide germline testing for a larger patient population.

Notably, a lot of men need to have germline testing. At the time, there was no streamlined infrastructure to deliver this service to men, thus, we had to figure out the best way to implement the idea. Ultimately, we decided to create a pilot study, which consisted of systematic delivery of germline testing for veterans with metastatic prostate cancer at the VA Puget Sound Health Care System.

In this study, we tried to test the systematic identification of men with metastatic prostate cancer that would qualify for germline testing. A research coordinator was in charge of prescreening patients at each prostate cancer clinic and would flag patients with metastatic prostate cancer. This helped oncologists understand which patients qualified for germline testing and it reminded them to talk about it with their patients.

Notably, when talking to patients with metastatic prostate cancer, there is a lot of information that must be covered. Oncologist cover their symptoms, their quality of life, their treatment plan, their prognosis, etc.

We created a structure that allowed us to notify oncologists when we identified patients that qualified for germline testing. Oncologists then discussed it with patients during regular follow-up appointments, informing them of the pros and cons. If patients were interested, they would sign a consent form and would provide a saliva test the same day of the appointment. This made the process simple and convenient. We tried to streamline the collection of saliva samples, as well.

If the patients agreed, genetic counseling was provided by the Color Genomics panel. The main idea of the study was to identify patients systemically and have oncologists provide germline testing, without creating an extra infrastructure when it came to genetic counseling. Genetic counseling is a different subunit, so patients don’t typically utilize the service. Out of all the patients approached, 84% agreed to perform germline testing and 90% of them completed the process at the time of data collection. Out of the 190 patients that were approached, 182 completed germline testing.

Recently, we had an exciting PARP inhibitor approval for patients with DDR mutations. If we identify those mutations, we can inform patients who have DDR mutations, such as 

, which puts them at risk of developing breast cancer, melanoma, or potentially pancreatic cancer. It’s important for them to understand that their family member could also be at risk. For example, their daughters or sisters could be at risk of developing breast cancer later on in life.

Therefore, by providing the service to our patients, not only can we help patients make the right decisions, but we can also help them inform their family members about the process and all that it entails. Encouraging more people to participate in germline testing could save lives.

What steps should be taken to help make germline genetic testing part of clinical practice?

There are several barriers of testing; some of them are on the patient’s side and others are on the providers side. One of the biggest barriers on the provider side is lack of infrastructure. In our old model, when a patient was sent to a genetic counselor, they first had pretest counseling, then testing, and then they had post-test counseling.

This is very time consuming, and, at this time, there aren’t enough resources to provide testing to all patients who qualify. We have to come up with alternative models that could help us streamline and use the resources available to provide this type of care to our patients.

In our study, genetic counseling was done through videos. The genetic counselor was initiated by a medical oncologist who was highly trusted by patients. However, another issue is insurance coverage. Currently, insurance companies don't cover cascade genetic testing. In cascade testing, when a patient has a mutation, family members are also recommended to undergo testing. Oftentimes, patients have a tough time getting coverage for this procedure. This being said, working on policy changes to ensure we have an infrastructure that could help take pressure off our patients is important. We want to provide patients and their families with everything that they need.

What other studies in this space would you like to highlight?

We have another method that helps us deliver germline testing to men with metastatic prostate, but it’s a much different mode. This model is web-based, and it is patient initiated. In this study, after oncologists provide the patients with all the information, patients then proceed to a website where they fill out their information and go through pre-test counseling. If they qualify, a saliva sample is sent to their home, and a genetic counselor later discusses the results over the phone. This model is great for some patients, although, it’s more challenging for others, especially for those who do not have good internet connection or are not savvy with technology.

Sokolova A, Miyamoto AN, Pouv DL, et al. Implementation of systematic germline genetic testing (GT) for metastatic prostate cancer (mPC) patients at the Puget Sound VA prostate oncology clinic. 

. 2020;38(suppl 15):1578. doi:10.1200/JCO.2020.38.15_suppl.1578

Alexandra Sokolova, MD, discusses the implementation of systematic germline genetic testing in veterans with metastatic prostate cancer appeared to be feasible due to high consent rates, especially with direct oncologist involvement.

Systematic Germline Genetic Testing Is Feasible in Veterans With Metastatic Prostate Cancer

 (Keytruda) demonstrated modest clinical activity in patients with advanced recurrent ovarian cancer, according to final results of the phase 2 KEYNOTE-100 trial that were presented during the 2020 ASCO Virtual Scientific Program. 

In the study, 376 patients with advanced recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were enrolled onto 2 cohorts: patients who received 2 or fewer prior lines of chemotherapy and had a platinum-free or treatment-free interval (PFI/TFI) of 3 to 12 months (cohort A) or those who received 3 to 5 prior lines of chemotherapy and had a PFI/TFI of 3 months or longer (cohort B). All patients received 200 mg of pembrolizumab for 2 years, or until disease progression, death, or unacceptable toxicity.

After a median follow-up of 37.8 months, results showed that the objective response rate (ORR) was 8.5% in all-comers, which comprised of 7 complete responses and 25 partial responses. The responses were not found to differ when stratified by lines of chemotherapy or PFI/TFI. However, there did appear to be a trend toward increased ORRs in patients with high PD-L1 expression (combined positive score [CPS] 10 or higher) across both cohorts, at 11.6% in cohort 1 and 18.2% in cohort B. Overall, the median duration of response was 10.2 months (range, 3.3+ to 35.4+).

The median progression-free survival (PFS) was 2.1 months in both cohorts. In cohorts A and B, the median overall survival (OS) was 18.7 months and 17.6 months, respectively.

“We found that, regardless of the degree of platinum sensitivity, there were no differences in the responses,” said lead study author Ursula A. Matulonis, MD. “This was very important. Most of our patients had high-grade serous cancer, however, there were also patients with clear cell cancer. The patients with clear cell cancer demonstrated a trend towards a higher response rate.”

, Matulonis, professor of medicine at Harvard Medical School, medical oncologist and chief of the Division of Gynecologic Oncology at the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute

 discussed the final results from the KEYNOTE-100 trial of pembrolizumab in patients with advanced recurrent ovarian cancer.

: Could you discuss recent therapeutic advances in ovarian cancer?

There is a lot going on for patients with ovarian cancer and treatment paradigms are frequently changing, especially for women who are newly diagnosed. Just a few weeks ago, there were 2 FDA approvals. PARP inhibitors were approved for use, after the completion of chemotherapy, in patients with newly diagnosed advanced ovarian cancer. In addition to this, the PAOLA-1 trial added olaparib (Lynparza) to bevacizumab (Avastin

In terms of patients with recurrent disease, many different avenues and treatments are currently being tested. Some of these data 

was presented at the 2020 ASCO Virtual Scientific Program. The treatment landscape for ovarian cancer is truly booming with activity right now. Investigators are now wondering: how robust are these results? How do they affect PFS and OS

? What toxicities are the patients experiencing? 

Could you elaborate on the historical challenges of immunotherapy in ovarian cancer?

Over a decade ago, multiple trials showed that newly diagnosed patients that exhibited T-cell infiltration did better than those who did not; they had an improved OS. Investigators now understand that the immune system plays a role in how cancer behaves. In addition to this, early results of ipilimumab (Yervoy) showed that a few patients had prolonged responses to the single agent.

When analyzing different checkpoint inhibitors in patients with recurrent ovarian cancer, the results are not overwhelming. They only seem to show moderate activity. Back in 2015, we started with a very small trial of nivolumab (Opdivo

), and this showed about a 15% response rate. In 2019, data from single-agent avelumab (Bavencio) showed a response rate of 10%. 

Additionally, updated data from the KEYNOTE-100 trial, which had a follow-up of over 30 months, studied single-agent pembrolizumab in 376 patients with advanced/recurrent ovarian cancer. The overall response rate was 8%. For patients with predominately platinum-resistant ovarian cancer, response rates with chemotherapy were quite low as well. In some instances, response rates with chemotherapy in the platinum-resistant setting is 0%. For example, in the AURELIA trial, topotecan had a response rate of 0% when used alone. Although, with the addition of bevacizumab, the response rate increased.

The use of liposomal doxorubicin demonstrated similar results, with response rates between 5% and 10%. Ultimately, this is a challenging patient population to treat.

In the KEYNOTE-100 trial, patients were broken up into 2 groups. Patients in group A were less heavily pretreated and received at least 1 to 3 prior lines of treatment; they had to have a PFI of at least 3 to 12 months. Conversely, patients in group B were more heavily pretreated. This group of patients could receive up to 6 lines of prior treatment and had to have a PFI of 3 months or greater.

Another factor was the level of PD-L1 expression. This is defined by a CPS, which looks at the PD-L1 expression in all types of cells. For CPS scores of 10 or higher, response rates were just below 20%.

In this study, the responses were similar, regardless of the number of prior lines of therapy. The level of platinum sensitivity also did not predict the responsiveness.

What does this mean for any potential role for pembrolizumab in clinical practice?

[In ovarian cancer], pembrolizumab does not yet have FDA approval. Its current approval is based on its FDA approval of microsatellite instability–high (MSI-H) tumors. The issue is, most of our patients have high-grade serous cancer, they do not have MSI-H tumors. In fact, only 8% of all ovarian cancers will have a MSI-H tumor. For high-grade serous cancer, MSI-H status is in about 2% to 3% of patients. This being said, that FDA approval of pembrolizumab in MSI-H tumors does not encompass most of our patients with advanced recurrent ovarian cancer. Currently, pembrolizumab, as well as other immunotherapy agents, are being tested as combination therapies.

There is certainly a lot going on in this space. Investigators are now trying to deduce the best way to incorporate immune-oncology agents into treatment plans for patients with microsatellite stable (MSS) tumors.

Have any new safety signals emerged in the KEYNOTE-100 trial?

There were no newly discovered safety signals in this trial. A majority of toxicities were fatigue, nausea, hyperthyroidism, hypothyroidism, colitis, etc. These are toxicities that are commonly seen when using immuno-oncology agents.

What is the main takeaway from this longer follow-up?

This study showed moderate activity in patients with recurrent or platinum-resistant ovarian cancer, regardless of the level of platinum sensitivity or the number of prior lines of treatment. This is much different than chemotherapy. In chemotherapy, response rates drop significantly depending on how heavily pretreated the patients are. That’s not what we’re seeing in this trial; we’re seeing very uniform levels of responsiveness.

Matulonis UA, Shapira R, Santin A, et al. Final results from the KEYNOTE-100 trial of pembrolizumab in patients with advanced recurrent ovarian cancer.

. 2020;38(suppl 15):6005. doi:10.1200/JCO.2020.38.15_suppl.6005

Pembrolizumab demonstrated modest clinical activity in patients with advanced recurrent ovarian cancer.

Pembrolizumab Continues to Show Modest Clinical Activity in Advanced Ovarian Cancer

The addition of apalutamide to androgen deprivation therapy (ADT), significantly improved overall survival (OS) and metastasis-free survival (MFS) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC), according to final results from the phase 3 SPARTAN trial.

With a follow-up of 52.0 months, 428 OS events had occurred. Median OS was significantly longer with apalutamide plus ADT versus placebo plus ADT, at 73.9 months versus 59.9 months (HR, 0.78; 95% CI, 0.64-0.96; 

 = .0161). When adjusted for crossover effects, apalutamide increased median OS by 21.1 months versus placebo (73.9 months vs 52.8 months). Apalutamide also extended median second progression (PFS2) by 14.4 months compared with placebo (55.6 months vs 41.2 months; HR, 0.55; 95% CI, 0.46-0.66; 

“In a nutshell, the results were striking. Patients who started on the placebo arm developed metastasis in 16 months and patients who started on apalutamide developed metastasis in 40 months. There was a 2-year improvement in MFS,” said lead study author Fred Saad, MD, FRCS. “Additionally, there was an improvement in the time the of PFS2 in patients who started on apalutamide compared with those who started on placebo, by over 50%.”

 during the meeting, Saad, the Raymond Garneau Chair in Prostate Cancer; a professor, chief of Urology, and director of Genitourinary Oncology at the University of Montreal Hospital Center; and the director of Prostate Cancer Research at Montreal Cancer Institute, discussed the final results from the pivotal phase 3 SPARTAN trial in nmCRPC.

: Could you provide background on the SPARTAN trial? What previous data have been seen with this drug in prostate cancer?

: SPARTAN is one of the first phase 3 studies to tackle the issue of nonmetastatic castration-resistant disease. We enrolled patients who were at high risk of [developing] metastatic [disease], and high risk was defined as a prostate-specific antigen (PSA) doubling time of less than 10 months. Patients were nonmetastatic, based on conventional imaging.

Patients were randomized 2:1 between apalutamide and placebo, which was the standard of care of just continuing ADT with nothing else, until patients became metastatic. The primary end point of the trial was MFS. We captured metastasis on imaging that was scheduled on regular intervals. The SPARTAN trial is very unique because we followed patients until second progression, so PFS2. This was quite unique; it was the first study I’ve been involved in, after 30 years of studies, that made an effort to capture PFS2. We tried to understand what patients received as subsequent therapy and we followed them until they progressed again. The main question we wanted to answer was, “Does starting in the nonmetastatic state make a difference, or should we wait until [a patient developed metastatic disease] before we start the subsequent therapy?”

Another unique quality of this trial was that patients were offered 

 at the time of progression. Patients were not left in limbo; they were offered an active agent that was also being used as the standard of care in the metastatic setting.

In a nutshell, the results were strikingly positive. Patients who started on the placebo arm developed metastasis at 16 months and patients who started on apalutamide developed metastasis at 40 months; this translated to a 2-year improvement in MFS, and this continued to carry over in the PFS2, where there was an over 50% improvement to time to PFS2 in patients who started on apalutamide compared with those who started on placebo.

Apalutamide received regulatory approval based on earlier results from this trial. Since its approval, how has

Clearly, the results regarding MFS were beyond what we expected when we started the clinical trial. It completely changed because it was the first agent approved for treating patients with nmCRPC in the high-risk category.

We now had something to offer our patients who were at high risk of metastases. We were very concerned of being in a state of limbo between having something to offer or doing nothing until their disease became metastatic. Patients found that strikingly unnerving that we would do nothing until their disease became metastatic. It didn’t make any sense, but we couldn’t do anything until we proved that we had something useful. To this end, this agent completely changed what we were able to offer our patients.

We still had people wondering whether delaying metastases was something that was really worth doing; they wanted to see overall survival (OS). OS is an extremely high bar when you are following patients very closely and are starting therapy in the metastatic state, much earlier than in the real world. Personally, I was cautiously optimistic because patients were treated very well; so many therapies were available in the placebo arm to catch up in terms of OS.

The data presented at the 2020 ASCO Virtual Scientific Program were truly striking. Even though patients received effective subsequent therapy very early in the placebo arm, we saw over a 14-month improvement in OS in patients who start apalutamide up front, rather than just waiting for metastasis to develop before starting very effective therapy. That is 3-4 times as long as the survival advantages that were seen when we start patients in the mCRPC state compared with starting them on placebo.

We went from a 4-month improvement when waiting for metastases, to a 14-month improvement when starting in the nmCRPC setting, which is probably very low-volume metastatic disease in reality. The importance of early therapy make a lot more sense now and I hope that all this controversy of whether or not to treatment the nonmetastatic state is diminished.

sets the agent apart from other androgen receptor inhibitors available in this space?

Apalutamide is certainly in line with the other pure androgen receptor–targeted therapies. The agent really differs from the androgen synthesis inhibitors like abiraterone; it is not acting on the production of androgen, but on the blockage of the androgen receptor, such as enzalutamide (Xtandi) and darolutamide (Nubeqa). Thus, they are very similar in terms of efficacy. Interestingly, we saw less fatigue with apalutamide.

We conducted a clean quality of life (QoL) analysis and it was very reassuring. In the asymptomatic state, when a patient has nonmetastatic disease, we gave a drug that would potentially have adverse events. However, patients remained with very stable QoL and showed no signs of deterioration. If anything, we saw a trend deterioration in QoL in the placebo arm.

Ultimately, all 3 drugs are very efficacious and well tolerated. It’s great that we now have multiple options for treating an entity that was once considered an orphan entity in terms of treatment options.

Did you learn anything else in terms of the safety profile of this agent with the longer follow-up data?

We already had a good idea of how well it was tolerated, along with potential issues that could arise. For example, a slightly higher [rate of] fatigue [was observed] with apalutamide than with ADT alone. However, this was expected; it’s a class effect of these agents. Some patients did develop a rash, although it was very tolerable in the vast majority. A percentage of patients developed low-grade hypothyroidism, although this was also very easy to manage and was not found to be too bothersome for most patients. This was something that we actually looked for.

We don’t know whether the other agents have this issue with hypothyroidism. This was an elderly population with a median age of 74. Patients were followed on apalutamide three times as long as they were on the placebo arm. Thus, we have three times the opportunity to capture negative adverse events (AEs). The bottom line is to ask whether these AEs negatively affected the QoL of our patients and the answer was no.

Is anything left unanswered from this study that you hope to address with future research?

Every time we answer a question, multiple questions arise. This leads to good research. The vast majority of patients respond very well to apalutamide. However, one of the unanswered questions is, “What should we do for patients who don’t respond well?” Over 90% of patients respond to this agent, but what is happening in the group of patients who do not respond? How should we treat those patients?

We are going to be presenting some data on PSA kinetics, on combining PSA with genomic profiles. We are trying to figure out whether there are better ways to find early signals where we may have to intensify therapy over apalutamide alone. Although this agent may work for a majority of the patients, there is a minority that we are still trying to figure out. Impressive OS data have been reported with apalutamide in the metastatic hormone-sensitive state. This being said, I believe a case is building for combination therapy.

I’m leading a trial that is examining the combination of 

 plus apalutamide up front to see whether we can do better than 

 alone. Hopefully, we will be able to report these results in the coming months.

Saad F, Small EJ, Chowdhury S, et al. Final survival results from SPARTAN, a phase III study of apalutamide versus placebo in patients with nonmetastatic castration-resistant prostate cancer. 

 2020;38(suppl 15):5516. doi:10.1200/JCO.2020.38.15_suppl.5516

The addition of apalutamide to androgen deprivation therapy, significantly improved overall survival and metastasis-free survival in patients with nonmetastatic castration-resistant prostate cancer.

Author | Erica DiNapoli

Articles

Atezolizumab/Radium-223 Combo Shows No Benefit in mCRPC, But Biomarker Work Planned

Systematic Germline Genetic Testing Is Feasible in Veterans With Metastatic Prostate Cancer

Pembrolizumab Continues to Show Modest Clinical Activity in Advanced Ovarian Cancer

Saad Highlights Striking Survival Benefit With Apalutamide in nmCRPC