We began this session talking about the future, and I’m really excited that 7 or 8 agents are in the clinic beyond the traditional PD-1 and PD-L1 inhibitors. I’d like to wrap up by hearing from each of you individually about what you’re excited about. What’s your source of excitement in the short term, in the next 1 to 2 years, that will really impact the patient experience? That’s why we do this. Anybody can start. Ketta, what are you most excited about in the next 1 to 2 years?

The most important step forward in endometrial cancer treatment is molecular profiling. We really made a great step forward, and we’ll use this information to guide our treatments: surgical treatment, possibly medical treatment, advanced disease treatment. This is the most important step forward, and we performed this more than in the treatment of other tumors—think about treating ovarian cancer and cervical cancer. Endometrial cancer treatment is a step in front of all the others in terms of the ecological malignancies.

We spent a lot of time on that during this 

® conversation because we recognize that education is important. Vicky, you had lots of very good comments—as all of you did. What excited you most though, to boil it down to 1 thing?

 Firstly, I’m very encouraged that we have the first phase 3 trial that investigated a nonchemotherapy combination in advanced recurrent endometrial cancer and essentially responded to a high unmet need. This is only the beginning. We have to accept that we have really reached the ceiling when it comes to chemotherapy for the management of endometrial cancers—at least advanced endometrial cancers. The many exciting studies that we have discussed teach us that we have much to learn. Surely, these studies will further impact the treatment landscape of advanced endometrial cancer. It’s an incredibly exciting time, and I’m privileged to be a small part of it.

It’s an honor to be a part of it. Nicoletta, I am going to give you the last word. So Dave, I want to hear from you next.

What a great group, one I’m honored to be sitting next to. I agree that the molecular signature in the up-front setting is exciting. We can be curing more patients while limiting toxic therapies and providing better quality of life and less long-term morbidity. That’s because of molecular signature. I really must applaud our European colleagues who’ve done a much better job, especially in the up-front setting. Then I challenged you earlier regarding curative and recurrent cancers and endometrial cancers. With these precision therapeutics, these unique combinations, we can cure recurrent uterine cancer in a certain subpopulation. Because of the wonderful work being done by this group and around the world, we can begin identifying those malignancies’ signatures, targeting them, and therefore improving our rate of survival and curative intent, even in the recurrent advanced setting.

I hope so. Nicoletta, it has been my pleasure to work with you for so many years. You always add such wisdom—as all of you do, don’t get me wrong—so I wanted to save the last word for you.

Like everybody else is, I’m extremely excited. We are amid a very impressive moment for the treatment of endometrial cancer. We’re moving forward. David was saying that we may be able to cure more patients in the recurrent setting, but I hope we’ll be able to prevent more recurrence by individualizing the adjuvant treatment. To me, the more fascinating areas are in the discussion of adjuvant treatment. It’s a long-lasting debate. With this personalized approach, we may be able to reduce the number of cases of recurrent disease. But the data in the recurrent setting are extremely encouraging. We now have efficient and effective immunotherapy for the treatment of advanced endometrial cancer. We have a combination regimen, lenvatinib plus pembrolizumab, that works in serous individual cancer, in nonendometrial cancer. This is very exciting. We have seen the data, and it’s all positive: OS [overall survival], PFS [progression-free survival], response rate duration. It’s exciting. For me, immunotherapy has changed the phase of many cancers during the last few years. Finally, this is happening. For the treatment of endometrial cancer, so I’m very excited.

This has been so educational and clear, and I hope the audience and those who participated virtually also enjoyed it. On behalf of 

®, I want to thank all of you. So long for now. Thank you.

Videos

Experts give insight on what they are looking forward to in the endometrial cancer space. 

The Future of Endometrial Cancer Treatment

 We have talked about I/O [immuno-oncology], DDR, WEE1, PARP inhibitors, FGF, IDO, selinexor—that’s a lot of stuff. Nicoletta, I haven’t heard from you because I was saving this question for you. Is there any surgical innovation in the treatment of endometrial cancer? Everything we just talked about—we began with you guys saying, “Radiation doesn’t do much.” Then we talked for an hour and a half about systemic therapy. We did not even mention the word 

. Is there anything new in the surgical landscape—you being a high-volume, very respected surgical expert—or is surgery just sort of there? It’s the bread of the sandwich, so to speak. What’s inside?

 You’re right. There have been some advances in surgery, of course. The role of minimally invasive surgery is very well recognized, for instance, particularly robotic surgery in the treatment of patients who are obese—which in the United States is a frequent situation. This has been a big advantage. Also, the sentinel lymph nodes—for years, we’ve been debating the role of a lymphadenectomy in the treatment of endometrial cancer. Is it curative? Is it diagnostic? What do we do after that? Now it’s well established that you can use—we perform only sentinel node biopsies in all patients, even patients who are high risk, because we believe that it’s mainly diagnostic and that it can guide us in terms of picking the proper adjuvant treatment.

In fact, you can spare most patients with major cancer from a lymphadenectomy. This is a big advantage if you think of the terrible sequelae that these patients had in the past, particularly if you’re considering the lymphadenectomy plus radiotherapy and the big lymphedema and so on. This isn’t trivial. This is really something important that we achieved in terms of surgical advances.

 Thank you for that expert opinion. In the United States, we say that because lymphedema is generally 2 things—it’s a lymphadenectomy and radiation together—we’re using less radiation. There might be a therapeutic benefit from removing the lymph nodes, not just 1 of them. Is there traction there? Because we’re not using whole pelvic radiation and with the potential therapeutic benefit of lymphadenectomy, should we swing the pendulum the other way, away from sentinel lymph nodes?

 I’m not sure. But you’re right: Radiotherapy plays a major role in the lymphedema. Therefore, if you just do a lymphadenectomy—let’s say with chemotherapy; after that, this will be less a problem—I don’t see any evidence that a lymphadenectomy can be curative in endometrial cancer. That’s why I believe that the sentinel node is more than enough.

Nicoletta Colombo, MD, PhD, reviews surgical advancements in endometrial cancer.

A Look at Surgical Innovations in EC

Dave, I want you to discuss this point: If PARP inhibitors work in this DNA damage-repair pathway, there’s emerging evidence that maybe WEE1 inhibition might be effective in treating serous cancer. A novel agent is pushing the envelope—it’s so much fun. Tell us about that as an opportunity.

It’s really interesting from a WEE1 standpoint. Joyce Liu presented at last year’s ASCO [American Society of Clinical Oncology Annual Meeting] on an agent—I believe it’s pronounced adavosertib. I’ll say that faster and try not to butcher it that badly.

AZD1775. It is 1 of the few instances in which I can remember the number. Keep telling the story.

The fun part is that I give Brad these entertaining pronunciations, so we always get a good laugh. We just talked a lot about the activity with the lenvatinib-pembrolizumab approach—about 30% in the recent AZD1775 trial. The WEE1 inhibitor, which was used to treat 34 patients, is something we have to take this with a grain of salt—34 patients who Joyce presented had a response rate of 29% with a duration response at 9 months. Everybody had to have 1 regimen of prior systemic chemotherapy, but it’s very interesting because this is an extremely heavily pretreated group of patients with 3 prior regimens. Three prior regimens with a response rate of 29%—in these patients with serous cancers, that’s a very impressive response. This is a very exciting opportunity that we are going to continue to see develop in the future.

The sponsor of that trial is continuing the study. There are at least 2 other WEE1 inhibitors, which are in the clinic. I don’t know if those studies are in the public domain, but there’s going to be an accelerated approval opportunity: Enroll 100 patients, show that there’s a response rate, and then we would design and execute the randomized phase 2 trial. I’m excited about that. I’m just going to roll through these new agents. We’ve already talked about 2. Ketta, CDK4/6 inhibitors really have revolutionized the ER [estrogen receptor]–positive landscape in breast cancer, but you have knowledge of a European trial and some other studies that have generally used an aromatase inhibitor plus CDK4/6. Tell me what you know about that.

 It was really exciting to see the results of the ENGOT-EN3-NSGO/PALEO trial last year during ESMO [European Society for Medical Oncology Congress]. We’re taking the opportunity with the lesson we learned in treating breast cancer. Mansoor Mirza was the PI [primary investigator], and he performed this randomized phase 2 trial. It was a small trial, but there was a strong proof of concept suggesting that when we combine the aromatase inhibitor—letrozole, in this case—with palbociclib, a CDK4/6 inhibitor, we are able to increase response rates and progression-free survival [PFS] with respect to letrozole alone. Particularly, the subgroup analysis suggests that the benefit is higher in patients who were pretreated with hormonal treatment. We are designing the phase 3 confirmatory trial, and if these results are be confirmed in the future, we may have this combination to treat all receptor-positive tumors.

This is 1 of the 4 groups of the molecular staging, so it all comes together. It’s really exciting.

 I want to make 1 correction. I may be wrong, but I don’t believe there’s a difference in the response rates, and these agents don’t seem to shrink tumors. They slow the growth. It is much different from when we discussed lenvatinib-pembrolizumab when we discuss these WEE1 inhibitors. In the future development of these drugs, a patient who is not symptomatic, a patient who does not have a rapidly growing tumor, is going to be impacted. So it’s very important, as we develop and look at these drugs, to know that is the problem. The CDK4/6 inhibitors don’t seem to shrink tumors when you combine them with AIs [aromatase inhibitors]; they keep disease stable.

That’s a great point. In breast cancer, they shrink tumors. Go ahead, Ketta.

 I just have a comment on the toxicity of this drug. In the ENGOT-EN3-NSGO/PALEO trial, we have a huge percentage of patients who discontinue treatment because of toxicity. We’re talking about a fragile population. These are older patients with several comorbidities, so this aspect should be taken into account in the next trial.

I’ll get to you in a minute, Nicoletta. Dave, I wanted to highlight you because you’re working on the POD1UM study, FGF/IDO1. Tell us about that.

 This was an interesting umbrella study. They are taking 2 parallel groups of patients: those who have been exposed to previous I/O [immuno-oncology] therapy and those that are not. Those who have not been exposed are using their PD-1 inhibitor, looking at both patients with high MSI [microsatellite instability] as well as the patients with deficiency, as a single-agent therapy. Those that have been exposed are taken out, and we are looking at the unselected population, which is the PD-1 inhibitor, plus the IDO1 inhibitor vs a select population of those with amplified or mutated in the FGFR1, FGFR2, and FGFR3 domain. When they add that, then they’re adding an additional agent that’s specific to the FGFR1, FGFR2, and FGFR3 patient population. We’re being smarter and more personalized in taking that molecular signature to the next level—which is not just 

, not just deficient or proficient MMR [mismatch repair], but taking it and utilizing next-generation sequencing on the tumor to have more rational therapeutics.

We talked about dostarlimab. Dostarlimab should be the seventh checkpoint inhibitor in the clinic. This 1 that you’re talking about, which was used in POD1UM, is called retifanlimab. Retifanlimab has been submitted to the FDA for approval for treatment for patients with anal cancer, especially HPV [human papillomavirus]–positive anal cancer, so that will be seven and then eight. That’s a very congested landscape, but it’s interesting.

Experts in endometrial cancer comment on novel targets of interest that are currently being investigated.

Novel Targets of Interest in EC 

 Let’s transition to discuss patients with recurrent endometrial cancer, or stage IV. They have the same risk of recurrence and death. Vicky, you’re a passionate advocate of this pembrolizumab-lenvatinib combination. You presented these data, which we’re very excited about. But we now have a study on the front line, right?

 It’s a chemotherapy-free regimen vs carboplatin-paclitaxel. Tell us about that.

Sure. This is based on the promising phase 2 results, and now the results of Study 309/KEYNOTE-775. This is essentially a randomized open-label trial to compare the safety and efficacy of lenvatinib plus pembrolizumab in combination vs carboplatin-paclitaxel chemotherapy as first-line treatment for patients with advanced or recurrent endometrial cancers. Essentially, patients who have stage III or stage IV recurrent endometrial cancer will be eligible. They may have received chemotherapy only if it was administered concurrently with radiation therapy, and patients will be randomized 1:1 to lenvatinib at 20 mg orally once daily, plus pembrolizumab at 200 mg every 3 weeks vs the standard paclitaxel-carboplatin IV [intravenous] every 3 weeks. The study has a dual primary end point of PFS [progression-free survival] and OS [overall survival]. The study is close to accrual, so we’re really happy to see that it accrued, and we’re looking forward to the data.

 I was a little skeptical until I saw the results of Study 309/KEYNOTE-775. Whoa—this whole idea of a chemotherapy-free regimen, which is what the study is, is so exciting. I’m excited, and I’m glad that it did enroll. Let’s continue this conversation. There are 3 ways to make anti–PD-1 and anti–PDL-1 agents better. One is to add a VEGF, and you told us about adding lenvatinib. The second is to add chemotherapy and radiation, and that’s what we’re going to talk about next. Certainly, the third would be an additional checkpoint inhibitor such as an anti-TIGIT or a CTLA4. But let’s talk about this idea of adding chemotherapy to checkpoints. This is the second opportunity to make single-agent checkpoints better. Nicoletta, 3 studies try to answer that question of I/O [immuno-oncology] therapy vs chemotherapy in the recurrent metastatic setting. Talk to us about those 3 studies.

You’re right. There are 3 trials that include more or less the same populations. We are talking about recurrent or metastatic advanced endometrial cancer, with all comers in all trials. They are stratified according to their MSI [microsatellite instability] status, but all comers are included. The first trial is the NRG-GY018 study, and it’s looking at a combination of carboplatin and paclitaxel plus a pembrolizumab placebo in treating stage III or IV recurrent endometrial cancer. pembrolizumab is the I/O together with carboplatin-paclitaxel. The other trial is the RUBY trial, and that accepted the same design, but dostarlimab is used instead of pembrolizumab plus chemotherapy or a placebo. It’s a study of the same population with the same stratification factors. The AtTEnd study is again, the same design, but it uses atezolizumab. We have patients with advanced or recurrent endometrial cancer. It’s a phase 3 placebo-controlled study enrolling patients. As far as I know, the first part of the RUBY trial is completed. Now it’s open for a second phase, which is a little different in the design. AtTEnd is also enrolling. We enrolled more than 350 patients, so we hope to conclude the accrual by the end of the year. I don’t have the details on the accrual, but I think it’s still enrolling patients. These are the 3 very similar trials; the statistical design is a little different, but they all look at OS and PFS. In the RUBY trial the primary end point is PFS, but they will look also at OS. In the AtTEnd trial, we have OS and MRD [minimal residual disease] as the primary end point. These are the 3 ongoing trials in the front line.

 NRG-GY018 uses pembrolizumab, RUBY uses dostarlimab, and AtTEnd uses atezolizumab. In the NCI [National Cancer Institute]–funded GY018, the MSI-high cohort is separate. It’s completely powered and completely analytical rather than welcoming all comers. It’s 2 studies rolled in 1, but you’re right. They’re very similar. Dave, what do you think of PARP inhibitors in treating endometrial cancer? You mentioned that RUBY will include that, but we do have a trial with durvalumab. Dave, tell us about DUO-E and how that’s different.

 The DUO-E trial is also looking at a carboplatin-paclitaxel backbone with durvalumab followed by durvalumab maintenance plus or minus olaparib. We’re really looking at this subpopulation of patients who are potentially going to benefit. We have talked about serous cancer, with the uterus being more similar to what we see in ovarian cancer—not molecularly; that is somewhat true—but there are some significant differences when we look at them molecularly. For me, it does make sense that some of those patients with 

 Kara, you had mentioned the RAINBOW trial. Now we have, I guess, RUBY part 2 or DUO-E— RAINBOW with PARP inhibitors. It seems as if we might really answer this important question. What do you think about PARP inhibitors in treating endometrial cancer?

They may play a greater role, particularly for patients with 

 mutations. For sure, we will see the results of this trial, and then we will better define when to use it in the algorithm of treatment, if we should use it in the adjuvant setting or in the first-line metastatic setting. Then we’ll see the results in treating ovarian cancer or how we can use PARP, which is another possible strategy, but they’ll play a role alone or in combination with immunotherapy.

 It’s been fun to develop this collaboration between ENGOT [European Network of Gynaecological Oncological Trial groups]—which is your group, Dave—and my group, GOG [Gynecologic Oncology Group]. With that collaboration, we can do all these trials. Many people would say they compete. We started our conversation—it’s good to have lots of opportunities in the trials, are different in subtle ways. I’m excited, and I’m grateful and thankful for that collaboration. There’s a whole other class of agents. There’s this trial called ENGOT-EN5, or SIENDO. Vicky, I know you’re pushing the envelope with these novel agents. Tell us about that study.

This trial is evaluating an agent called selinexor, which is a novel oral selective inhibitor of nuclear export. Essentially, this agent forces the nuclear retention and activation of tumor-suppressor proteins. This drug, in combination with low-dose dexamethasone, is already approved to treat relapsed/refractory multiple myeloma. It’s also approved to treat relapsed/refractory diffuse large B-cell lymphoma. It has shown activity across a number of other hematologic malignancies and solid tumors. It has shown some efficacy treating endometrial cancers that have been previously treated. In the absence, as yet, of an approved maintenance therapy for patients with endometrial cancer following a platinum-based therapy, this drug is being evaluated in a maintenance setting in patients who have achieved CR [complete remission] or PR [partial remission] following platinum and taxane chemotherapy.

 This study is interesting based on its mechanism of action, which you talked about, and also the setting. This is the Athena of endometrial cancer: You finish your chemotherapy, and then you’re randomized. All options need to be on the table. All classes of agents need to be studied. It’s collaborative, as that trial is, the ENGOT-GOG collaboration.

Key opinion leaders take a look at the evolving treatment landscape in endometrial cancer, discussing ongoing trials in the space.

Insight on Ongoing Trials in EC 

I’d like to incorporate the molecular features into the selection of adjuvant therapy. Ketta, talk to us a little about PORTEC-4a and the TAPUR trial? Thank you.

The PORTEC-3 trial gave us a lot of interesting information. Even though there was retrospective analysis, it suggested that, according to the molecular feature that the tumor presented, the response to treatment may be quite different. In particular, the patients with 

mutations have a good prognosis; they probably don’t need any adjuvant treatment. On the contrary, the 

 mutations tumors had a worse prognosis and seem to benefit with chemotherapy. The intermediate prognosis is that the MMR (mismatch repair) deficient population seems not to have such a good response to chemotherapy when we combine chemotherapy plus radiation treatment. These patients would require another kind of treatment, like I/O [immuno-oncology] therapy. The last group—the group with no specific molecular characteristics—gained a little benefit from chemotherapy. Taking in consideration all these aspects, we are designing a new generation of clinical trials that use this information to guide adjuvant treatment. The first trial using this information was the PORTEC-4a trial. It was very interesting because the PORTEC-4a trial was an adjuvant radiotherapy trial for patients with stage I intermediate-risk endometrial cancer. Most of us do not consider radiotherapy a treatment to offer to this patient because it increases local control but has no impact on overall survival. According to only clinical characteristics, we risk overtreating a lot of patients when we offer radiotherapy to all of them

PORTEC-4a is very interesting because it divides patients into 3 groups according to the molecular characteristic: low risk, intermediate risk, and high risk. The study doesn’t offer any treatment—no radiation—to the low-risk group while offering radiation treatment only to the intermediate- and high-risk groups. This trial represented the first example of a trial that used the molecular characteristics of the tumor to guide adjuvant treatment. It’s the first but not the only 1; a lot of trials are arriving. In particular, there’s a huge international project called the RAINBOW trial. They use different treatments according to the molecular characteristic in the adjuvant setting. In this scenario, patients with tumors who have 

 mutations receive chemotherapy and then PARP inhibitors for 2 years. Those with MMRD [mismatch repair–deficient] tumors received radiation treatment and then immunotherapy for 1 year. Those with MMSP [malignant melanoma of soft parts] tumors received radiation treatment and hormonal treatment, with adjuvant as maintenance. Those with 

 tumors do not receive any adjuvant treatment, so it’s a completely different way to approach treating endometrial cancer. It is straightforward in the treatment of the disease.

We’re excited about that. That’s on topic with the adjuvant treatment. There’s another international trial that ENGOT [European Network of Gynaecological Oncological Trial groups] and the GOG [Gynecologic Oncology Group] are collaborating on. It’s called KEYNOTE-B21, and it’s basically taking patients with newly diagnosed endometrial cancer positive nodes—even patients with 

 mutations, to your point about molecular characterization—and treating them with chemotherapy and adding a placebo or pembrolizumab. Radiation is elective. This whole adjuvant space and molecular partitioning are both really important.

Experts discuss the importance of incorporating molecular features into the selection of adjuvant treatment.

Incorporating Molecular Features into Choosing Adjuvant Therapy 

Let’s talk about sequencing. It’s clear that carboplatin-paclitaxel is the frontline therapy. Maybe LEAP-001 will show that pembrolizumab-lenvatinib is a better option, but for now that’s where we are. What I’m seeing people say is that pembrolizumab and lenvatinib have these associated adverse reactions; this place has a platinum-sensitive endometrial cancer recurrence. I’m going to change the sequencing, and I’m not going to use pembrolizumab-lenvatinib as a second line treatment. I’m going to give the patient another round, not of doxorubicin or paclitaxel—this was done in Study 309/KEYNOTE-775—but I’m going to re-treat them with carboplatin-paclitaxel, particularly in the adjuvant setting. Now they have recurrence. Is there any rationale, Nicoletta, to have a platinum-sensitive recurrent endometrial cancer and re-treat with platinum? Or is that just an inappropriate extrapolation from treating ovarian cancer?

I do believe that platinum and Taxol [paclitaxel] are effective drugs in endometrial cancer, so I don’t think they should be definitely abandoned. In terms of rechallenging, we don’t have specific trials for endometrial cancer setting the cutoff for the treatment or platinum sensitivity. We frequently use the experience treating ovarian cancer to treat endometrial cancer. However, the results of rechallenging with platinum in endometrial cancer are a little less brilliant compared with ovarian cancer. Therefore, there is definitely space and a need for improvement in this setting. For patients with deficient mismatch repair, it is easier. If you have a recurrence and the patient receives adjuvant treatment, I would go for I/O [immuno-oncology] very easily before using chemotherapy. It’s more difficult and challenging for the patients with proficient-repair endometrial cancer in this metric, not MSI [microsatellite instability]–high cases. Here, I would use a lot of clinical judgment. For instance, if you perceived that the patient had the benefit from adjuvant treatment because she has a long disease-free interval—she was high risk, but she has a very longer disease-free interval—I would probably use a platinum to start with. I would keep the new combination for later on because, as we have heard, this is a very attractive combination, a very effective combination, but of course there’s toxicity. Therefore, it’s not that we doubt that platinum is without toxicity, but we’re used to this platinum and toxicity, so whenever you believe that this may be effective, I would probably try this drug first and then go to the combination or the new combination.

-mutated subgroup that you nicely outlined, which are frequently cirrus under the microscope—although not universally—does that influence that decision of sequencing? Or are you going to do what Nicoletta suggested, which is basically use this as a second line as long as it’s not MSI-high? I’m probably going to go to pembrolizumab and lenvatinib.

According to the subgroup analysis of the PORTEC-3 trial, for sure, but the clear impression is that 

 tumors gained more benefit from chemotherapy. These are the data we have now and possibly in the future, this tumor will be treated with more than chemotherapy. Some very interesting ongoing trials suggest that these patients may also derive benefits from PARP inhibitor maintenance, and we have some trials addressing these issues. Based on the data we have—particularly in the setting that Nicoletta reported—for patients who have received only adjuvant treatment with a long remission, I would go with chemotherapy.

I have to call the group out here. There is 0 data that supports re-treatment after prior exposure. If it would have worked, the patient would have been cured of their disease. For stage I serous cancer of the uterus, you wouldn’t have given them chemotherapy. We cure 90%-plus of those patients. It would have worked. You wouldn’t have a recurrence. We need to challenge this dogma. We have extrapolated information from ovarian cancer. There are little to no data to support re-treatment with the carboplatin-paclitaxel. Vicky, you told us 30% of patients had an overall response rate. When we look at those who had tumor shrinkage, we’re talking about two-thirds of patients. I see more of that data. When you really looking at this—I challenged this dogma myself—for that patient who has high-volume disease, response rates with pembrolizumab and lenvatinib are pretty good. I want to question us on this, and I don’t think we should continue with this dogma. We need to research it further.

Do you want to rebut that? Then Vicky, I have 1 question. And then we’ll wrap it up. Go ahead if you want to make a comment.

We have a trial ongoing. The LEAP-001 trial will answer those questions. It’s just matter of time. We’ll see. Of course, maybe it is a stupid dogma, yet we do see a response also with chemotherapy when you rechallenge them. It’s not that they don’t respond. They respond with both regimens, so let’s wait for the LEAP-001 trial, and then we’ll have the answer.

I have a short comment. We have retrospective data suggesting there’s a rule for rechallenging with platinum. Following the European guidelines, we introduced this hypothesis. I agree with you, David, that this hypothesis was mainly based on the absence of an alternative, because when the clinician has more therapeutic alternatives, they can do more. Ten years ago, if we had all the alternatives we’re facing today, we would not request to rechallenge with the drug. But during the time we have no alternative, we have the opportunity to reintroduce and see a response to platinum. In the near future, we’ll have more data, and we’ll be able to answer more accurately what the appropriate sequences and algorithms are.

Very diplomatic. I love that. Vicky—and also those of you who are involved in this trial—you’ve been very careful not to provide confidential information. I respect that, but we all want to know when the drug will be available, particularly in Europe, where it’s not available. Quite frankly, we also want to know when it will be FDA approved because the marketing will change. You can’t really market the data, or promote it, until it’s FDA approved. The press release was in December. Generally it takes 10 to 11 months, so that would be October to November for FDA approval? Is that a reasonable assumption?

 That’s a very reasonable assumption. Everybody involved is trying to proceed as diligently as possible. That’s what I can say to that. Can I just make 1 point, though, about the chemotherapy rechallenge question? I actually agree. There is no 1 size that fits all. The pembrolizumab data are very compelling. The efficacy is profound, and it is a robust regimen, but we have to consider the patient who is sitting in front of us. The truth is that not everybody will be robust enough to receive pembrolizumab and lenvatinib. Those patients may benefit from chemotherapy platinum-based free challenges. Of course, we must consider the patients who have the lower-grade endometrial adenocarcinomas. We didn’t talk about hormonal therapy, but obviously that’s also on the table for some of our patients.

Experts in endometrial cancer comment on therapeutic sequencing in endometrial cancer.

Bradley J. Monk, MD, FACS, FACOG, University of Arizona, Creighton University, & Arizona Oncology Practice of US Oncology

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