Bradley Monk | Gynaecologic oncologist and Medical Director, the Late-Stage Clinical Research Program, Florida Cancer Specialists & Research Institute, USA
Your career in gynaecologic oncology has spanned several decades. What initially drew you to this field, and how has it evolved since you first started?
As a young man trying to figure out what I would and should do with my life, it occurred to me, and it’s still true, that cancer is going to kill a lot of us, maybe most of us.
So, I thought I should join the fight. It is that simple. I didn’t have a personal connection to someone who had died from cancer; I just knew it was a major threat, and I wanted to help. Second, gynaecological oncology is the only specialty in medicine that specialises in cancer. So, for example, among radiation doctors, radiation oncologists specialise in radiation; surgical oncologists specialise in surgery; medical oncologists specialise in systemic treatment; and so on. I specialise in cancer, gynaecologic cancer, cancers of the female reproductive tract.
For how the field has evolved since I started is, in the beginning, it was mostly a surgical specialty, and surgery was hard. Now we individualise the surgery, we do minimally invasive surgery. If it’s an advanced ovarian cancer, we give neoadjuvant chemotherapy. So, now the predominant portion, because we’re nimble, is systemic therapy; that is chemotherapy. Over the last several decades, we’ve seen more than 20 new indications, and several medications approved, in all of our tumour types as a result of what I’m passionate about: clinical research.
Looking back at your early training at the University of Arizona, USA, and your fellowships at University of California, Los Angeles and University of California, Irvine, USA, how did those experiences shape your passion for research and clinical care in gynaecologic cancers?
It takes several components to be successful in clinical trials, research, and even patient care. You have to be motivated and consistent because there is no all-at-once in life. But what is just as important as motivation and consistency is mentorship. I am a product of elite mentors, including Dave Alberts, the Cancer Center Director at the University of Arizona, Tucson, USA, a very famous gentleman in gynaecologic cancer. My mentor during residency was Jonathan Barrick, who went on to become the OBGYN Chair at Stanford University, California, USA; and then Philip de Siya, who was the President of the Gynecologic Oncology Group (GOG). There were also many others, including Maury Markman, President of Medicine & Science, City of Hope National Medical Center, Atlanta, Chicago and Phoenix, USA, who has been a fantastic mentor to me. I’m a product of that, and I try to pay it forward and mentor others because it is a team effort as we work together in the fight against cancer.
With your extensive research in cervical, endometrial, and ovarian cancer, how do you see the field of gynaecologic oncology evolving over the next 5–10 years, especially considering recent innovations discussed at ESGO?
Last year alone within the gynaecologic cancer space, we had six FDA approvals. I founded the GOG Partners Research Organisation over 15 years ago, and at the time, we had 4 years without any approvals, then we went another 4 years without any approvals. In total we had 8 years, with no new FDA approvals. We’ve witnessed remarkable advancements, especially in cervical and endometrial cancers. Before last year, we saw breakthroughs with chemotherapy and anti-angiogenic treatments. The evolution of treatments in this field is undeniable.
Anti-angiogenics remain a crucial part of gynaecologic cancer treatment, particularly in endometrial cancer, where lenvatinib and pembrolizumab received second-line approval for pMMR endometrial cancer. Angiogenics were among the first novel agents in this field and marked the first targeted therapy ever approved for a gynaecologic cancer (cervical cancer). It was FDA-approved in 2014.
That same year, PARP inhibitors also gained approval. Over time, their use has expanded from later-line treatments to earlier in the treatment process. We now have biomarkers such as Homologous Recombination Deficiency (HRD). Immunotherapy is now approved for cervical and endometrial cancer. At ESGO, we had a very provocative, positive immunotherapy, pembrolizumab trial.
Another breakthrough has been antibody–drug conjugates. Last year, two antibody–drug conjugates received full FDA approval, telisotuzumab vedotin in cervical cancer and rituximab and tancine tissue factor and folate receptor, respectively.
When you look at the progress we’ve made in chemotherapy, anti-angiogenics, PARP inhibitors, immunotherapy, and antibody–drug conjugates, it’s clear how far we’ve come. But we’re not stopping here.
There are still exciting new opportunities on the horizon, including hormonal therapies, radionuclides, and T cell engagers. The ESGO 2025 Congress just concluded. What were some of the most exciting advancements or discussions that stood out to you during the event?
I would like to thank the organisers for the 26th European Congress of Gynaecologic Oncology, held February 20th–23rd in Rome, Italy. This is a very exciting and beautiful meeting, and if you didn’t attend this year, you should attend next year.
The main Phase III trial presented was KEYLYNK-001, also known as GOG trial 3036. It was also an European Network of Gynaecological Oncological Trial (ENGOT) study, with ENGOT serving as the lead group among 43 organisations. The presenting investigator, Ignace, represented ENGOT on behalf of GOG.
As I mentioned, the fourth innovation is immunotherapy. While it is approved for cervical and endometrial cancer, it has not yet been approved for ovarian cancer. However, we now have three studies, including the DUO-O trial with durvalumab, which is particularly exciting as it explores the combination of olaparib and durvalumab in the frontline setting.
We also have another study involving dostarlimab and niraparib, called FIRST, with a positive press release. It hasn’t been presented at ESGO yet. However, the KEYLYNK-001 trial (GOG 3036) was presented, and it addressed several key questions. One of these was whether there’s an opportunity to add immune therapy, specifically anti-PD-1 pembrolizumab, to the commonly used treatments in newly diagnosed advanced ovarian cancer, which often include PARP inhibitors, bevacizumab, or both. The short answer, similar to the DUO-O trial with durvalumab, is no.
Immunotherapy alone, as seen in other studies, including some I’ve led, added to chemotherapy in newly diagnosed advanced ovarian cancer, isn’t sufficient. What the DUO-O and KEYLYNK-001 trials demonstrated, and what the FIRST trial will likely show as well, is that when you combine a PARP inhibitor (discovery number three) with immunotherapy (discovery number four), the results are striking. There is an important benefit in prolonging progression-free survival and not having a decrement in overall survival, because it’s not powered for overall survival of adding either durvalumab and olaprib, or pembrolizumab and olaprib versus chemotherapy.
So, what about the role of bevacizumab? Bevacizumab was included in KEYLYNK-001, and if you wanted it, it was provided free of charge to the patient. But why might you not receive it? There are several contraindications, such as if the patient has an open wound, as I was just dealing with one case like that it’s not a good candidate for bevacizumab. Other contraindications include kidney disease, uncontrolled hypertension, and bevacizumab is generally not used in patients who have had a complete resection. It’s more commonly used in cases with large-volume disease or Stage IV cancer. While bevacizumab wasn’t the focus of analysis in KEYLYNK-001, it was available to those who needed it. So, don’t focus too much on whether or not to use bevacizumab, because it essentially serves as a surrogate for disease-related factors.
Some of the other immunotherapy studies, including those I’ve led, such as Javelin 100 and Athena Combo, were negative. There are reasons for this. The key difference between those studies and positive ones like DUO-O and KEYLYNK-001 is that immunotherapy requires a tumour microenvironment to be effective. For instance, if the tumour is surgically removed or destroyed with chemotherapy, the microenvironment is disrupted or even non-existent, making it difficult for immunotherapy to work. In a study I presented at the European Society for Medical Oncology (ESMO) Congress last fall, Athena Combo involved patients who had responded to chemotherapy, where the cancer was essentially gone, and in this case, there was no tumour microenvironment to educate with immunotherapy and PARP inhibitors. On the other hand, in DUO-O and KEYLYNK-001, the tumour microenvironment was intact, and interestingly, the more cancer present, the better the treatment worked. This is a positive outcome because it targets the harder-to-treat populations. So, KEYLYNK-001 builds upon the results of DUO-O, which was presented in its final form in June last year.
Immunotherapy is given alongside chemotherapy and continued during the maintenance phase. In the maintenance phase, PARP inhibitors are then added. Interestingly, this approach doesn’t seem to require specific biomarkers, such as a PDL-1 score or an HRD score. While there is some enrichment with HRD, it’s not essential, unlike in the case of combining PARP with bevacizumab in the PALO-1 study, where biomarkers like HRD are critical.
At ESGO 2025, there was significant focus on personalised medicine. How do you see this approach evolving in gynaecologic oncology, and what role do you think it will play in future treatment strategies?
Personalised medicine, surprisingly, is a little controversial, because you want to individualise, which is different than personalised. Let me give you an example, an antibody–drug conjugate, such as for cervical cancer, is individualised, it is only used in a certain population, but it’s not biomarker-informed, which, in my opinion, is a good thing, because you don’t need that biomarker to work. On the other hand, mirvetuximab soravtansine, an antibody–drug conjugate for ovarian cancer, is only approved in the tumours where the expression level in 75% of the cells is two plus or more, which is about a third. So, you can say, that’s great, we know who it works in. I would say it is absolutely necessary to know who it doesn’t work for. But the downside is we don’t want to identify where it doesn’t work. We want to give it to as many patients as possible.
Then certainly these other medications, such as PARP inhibitors, have molecular signatures such as BRCA. All BRCA is homologous recombination repair and efficient. For immunotherapy, in recurrent cervical cancer we use a PDL-1 score. In endometrial cancer, we use mismatch repair deficiency assessment or MSI-high. So, there are places where it’s important. Every cancer is individualised, treatment-wise, best for the patient, but sort of the personalisation the biomarker needs to be understood in its context.
What challenges do you think persist in this field, and how are congresses like ESGO helping to address these gaps through research, collaboration, and innovation?
I want to discuss the mechanisms of resistance. For example, platinum (usually carboplatin, and sometimes cisplatin) is commonly used, but we still don’t understand the mechanisms of platinum resistance. It’s interesting, right? We certainly don’t understand the mechanisms of resistance to anti-angiogenics or immunotherapy. We know a little bit about PARP inhibitor resistance, but it’s heterogeneous. Not every cancer is resistant in the same way. If we don’t understand how the cells are resistant, we can’t defeat it. So that’s, really important. Number one, mechanisms of resistance.
Number two, which is related, concerns the new antibody–drug conjugates that use topoisomerase payloads. With these, you’re probably looking at a one-and-done treatment. We have many antibody–drug conjugates in the clinic now, but if they share a similar mechanism of action for the payload, you’re likely to get one round. If the tumour becomes resistant, it’s probably not going to respond to another topoisomerase-based therapy. Of course, if there’s a loss of the target, such as switching from HER-2 to TROP-2, it might be possible to try a different approach. However, based on the preclinical data, some of which was presented at ESGO, the mechanisms of resistance to these antibody–drug conjugates align with traditional mechanisms of chemotherapy resistance. But as I’ve already mentioned, we still don’t fully understand them, things like efflux pumps, and how DNA damage and apoptotic pathways are activated.
Finally, let’s talk about sequencing. Suppose you have three options: an anti-HER2 antibody-drug conjugate, one of these other antibody-drug conjugates, and hopefully, TROP-2 will be approved soon. Which one do you use first? The problem is that we haven’t studied sequencing well enough. If I were to add a fourth point, it would be comparative effectiveness. Sequencing is obviously important, but so are head-to-head comparisons. So, if I get it, the question is, which one is next, but also which one is better? And as a general rule, in drug development, we don’t compare drug A versus drug B. We generally only study drug B after drug A. So, we have a lot to do with sequencing and understanding the mechanisms of resistance and comparative effectiveness.
