Editor’s Note: The 2024 CSCO Ovarian Cancer Session covered various topics, including surgical treatment for ovarian cancer, drug therapy for advanced-stage patients, and data from novel drug research. Dr. Lingying Wu from the Cancer Hospital Chinese Academy of Medical Sciences chaired the session, where Dr. Oliver Dorigo from Stanford University delivered a report on “Cellular Therapy for Ovarian Cancer,” and Dr. Jianyu Rao from University of California, Los Angeles(UCLA) discussed “Precision Treatment Strategies for Ovarian Cancer.” After the session, the three experts participated in Oncology Frontier’s “CSCO International Perspectives” column, engaging in an in-depth discussion on cellular therapy and precision treatment strategies for ovarian cancer.1. After seven years, Oncology Frontier is honored to invite the three of you for another roundtable discussion. Could you first share your impressions of the 2024 CSCO Conference?
Dr. Lingying Wu: Seven years ago, the three of us had an academic discussion at the 2017 CSCO Annual Meeting. The pandemic hindered in-person gatherings in recent years, but this year, we finally reunited in beautiful Xiamen. The scale of the 2024 CSCO Conference is massive, bringing together many international and domestic experts. The agenda covered clinical guideline interpretations, hot topics in clinical practice, and new developments in technologies and research. For example, the Gynecological Oncology session included discussions on CSCO guidelines, the latest standard treatments, international research advancements, and domestic progress. We also saw many achievements from China in the papers presented, which were far more prospective and scientifically rigorous compared to the retrospective studies of the past. I attended other sub-specialty sessions and found them just as packed as our gynecology session. The academic exchange atmosphere and the design of the agendas reached an unprecedented level at the 2024 CSCO.
Dr. Oliver Dorigo: I’m very grateful to Professor Wu for inviting me to this discussion once again, and I must say that Dr. Jianyu Rao is also a close friend. My first CSCO experience was in 2017, which was a wonderful one. Unfortunately, soon after, the pandemic hit, preventing us from attending important events like CSCO in person. International collaboration is crucial for research in gynecological cancers, and I’m impressed by CSCO. I agree with Professor Wu—now we have more trial data to guide clinical decision-making. Over the past decade, precision oncology in ovarian, endometrial, and cervical cancers has seen tremendous advancements, with biomarkers emerging to guide treatment decisions. These developments were highlighted at the 2024 CSCO, generating significant interest. I was thrilled to see full attendance in the sessions and look forward to returning to future CSCO conferences to present my own research findings.
Dr. Jianyu Rao: I completely agree with Professor Wu and Dr. Dorigo. CSCO is an incredibly important conference, not just in China but with significant international impact as well. Although the pandemic slowed down research, collaboration, and exchange, both China and the U.S. have made significant progress in the oncology field over the past seven years. Against this backdrop, CSCO provides a vital platform for exchanging information and fostering international cooperation in the cancer field, and I’m honored to be part of this conference.
2. What types of cellular therapies show promise in treating ovarian cancer? Could you share some recent research findings on cellular therapy for ovarian cancer?
Dr. Oliver Dorigo: This is a very important question. CAR-T cell therapy for solid tumors is a topic of great interest. We’ve successfully developed CAR-T therapies for hematologic cancers such as leukemia and lymphoma, with some already approved for clinical use. However, progress in solid tumors hasn’t been as fast as we hoped. Many trials are ongoing worldwide, and China is leading some of these efforts (I believe Professor Wu is involved in some of these trials). These trials explore CAR-T therapies, other gene-modified T-cell therapies, and therapies involving other cell types like macrophages, making this field full of opportunities. We’re still in the early stages, but we’ll learn a lot from these trials.
Currently, most ovarian cancer patients can tolerate CAR-T therapy. Many ovarian cancer patients have undergone multiple rounds of chemotherapy, raising concerns about whether they can tolerate the lymphodepletion required for CAR-T therapy, which can be toxic. However, I believe the future of cellular therapy is bright. One key challenge is selecting the right antigen, as Dr. Rao pointed out in his CSCO session. Identifying the right antigen is crucial—what proteins or peptides are highly expressed in ovarian cancer? We need to determine which antigens are overexpressed on tumor cells to make CAR-T therapy effective. In my presentation, I discussed using intraperitoneal CAR-T therapy for ovarian cancer. Since ovarian cancer is typically confined to the abdominal cavity, this is a unique feature that allows us to deliver CAR-T cells directly to the tumor site.
There is still much to learn about cellular therapy for ovarian cancer, and I’ll continue following the research developments in China as well.
Dr. Jianyu Rao: I fully agree with Dr. Dorigo. He’s an expert in cellular therapy, especially for ovarian cancer. The field of cellular therapy for ovarian cancer is advancing rapidly, with many new developments. We’ve discussed the challenges of finding the right approach for solid tumors, which are quite different from blood cancers. One major obstacle is tumor heterogeneity, making it difficult to identify key antigens. These unresolved issues highlight the importance of international collaboration—scientists and oncologists must work together to address these challenges and avoid duplicating research.
Dr. Lingying Wu: Cellular therapies have proven more effective in treating hematologic malignancies, especially lymphomas, than solid tumors. For solid tumors, China is still in the research and exploration phase. Early studies have shown that some cellular therapies can be effective in treating ovarian cancer, but the findings are still preliminary. Our team is also planning to conduct some cellular therapy research soon. I agree with Professor Rao’s point about strengthening international collaboration and avoiding redundant research. I hope China can achieve breakthroughs in cellular therapies and catch up with the global advancements in this field.
3. Although China hasn’t yet produced mature results in ovarian cancer cellular therapy, there has been significant progress in the research of PARP inhibitors, immunotherapy, and ADC drugs. What are your thoughts on these developments?
Dr. Lingying Wu: In the field of ovarian cancer, apart from our participation in international collaborative studies, Chinese pharmaceutical companies and domestic colleagues have conducted extensive research on domestically developed drugs, some of which have garnered international attention.
Regarding PARP inhibitors, two Phase III randomized controlled trials (RCTs)—PRIMA and PRIME—showed that niraparib significantly extended progression-free survival (PFS) in the overall population when used as first-line maintenance in newly diagnosed advanced ovarian cancer. The NORA study confirmed that niraparib maintenance therapy prolonged PFS compared to placebo in platinum-sensitive recurrent ovarian cancer. Hengrui’s PARP inhibitor fluzoparib has also succeeded in both frontline and subsequent treatment settings. The FZOCUS series of studies showed that fluzoparib is effective in the general population for first-line maintenance and in platinum-sensitive recurrent patients with different BRCA statuses, with a one-year PFS rate close to 70% in the recurrent treatment cohort. The 2024 CSCO Conference also presented two studies on first-line maintenance therapy with PARP inhibitors: the overall and subgroup results of the FZOCUS-1 study on fluzoparib and the FLAMES study on senaparib. Data from multiple domestic PARP inhibitor studies have been presented and discussed at international conferences, receiving recognition from global peers.
Regarding immunotherapy, although ovarian cancer is considered an immunologically “cold” tumor, immunotherapy can still benefit certain advanced or recurrent patients. Immune checkpoint inhibitors and cellular therapies are worth further exploration.
Antibody-drug conjugates (ADCs) are also a hot topic in ovarian cancer. Chinese pharmaceutical companies are developing ADCs targeting multiple antigens, including TROP-2, B7-H4, B7-H3, HER2, and folate receptor alpha (FRα), and several bispecific antibodies are under investigation. China’s clinical research is now almost in sync with international efforts, and we’ve even seen some first-in-class drugs emerge.
Dr. Jianyu Rao: Cancer is not a single disease but a collection of diseases, and tumor heterogeneity is a major issue. There are also differences in the incidence patterns across different ethnicities. For example, the BRCA mutation rate may vary among ovarian cancer patients from different racial backgrounds, and the incidence of EGFR mutations is much higher in Asian lung cancer patients than in other populations. This underscores the importance of international collaboration in precision medicine. I’ve been involved in research across the U.S., Europe, and other regions and have seen progress in all areas. The West Coast of the U.S. has a large Asian population, so I’m very pleased to see China’s progress in precision cancer treatment, as it benefits not only Chinese patients but also helps doctors in the U.S. manage Asian patients.
4. Dr. Rao, you discussed precision treatment strategies for ovarian cancer at the 2024 CSCO. Could the three of you share more insights on this topic?
Dr. Jianyu Rao: Precision treatment for ovarian cancer is a vast topic, but we must remember that precision diagnosis is the foundation of precision treatment. As a pathologist, diagnosing cancer isn’t just about confirming that it’s cancer. It requires a more detailed analysis, such as genetic testing and protein expression profiling, to help clinicians choose targeted drugs based on biomarkers. Precision diagnosis and precision treatment must go hand in hand for successful outcomes.
Dr. Lingying Wu: At the 2024 CSCO conference, I gave a presentation in the pathology session on the “Treatment Strategies and Pathological Testing Needs for HRD and BRCA-Positive Ovarian Cancer Patients.” The need for pathological testing is crucial for more accurate diagnosis and treatment. Both ADC and PARP inhibitor studies have shown that the efficacy of these drugs can vary based on BRCA mutation status, homologous recombination deficiency (HRD), and homologous recombination proficiency (HRP). Therefore, pathological testing is invaluable in guiding clinical treatment and predicting prognosis.
Dr. Oliver Dorigo: I fully agree with Professor Rao. Today, precision treatment wouldn’t be possible without pathologists. As a surgeon, I can’t operate without an anesthesiologist, and similarly, we depend on pathology information. Clinicians often struggle to identify the correct targets, interpret pathology results, or understand the pathways involved, which is where pathologists provide critical insights. There must be close collaboration and communication between pathologists and clinicians. Pathologists may not always know which targets are of interest to clinicians, so this requires ongoing education and mutual understanding. That’s how we make progress.
In the U.S., FRα has been a hot target for ADCs in ovarian cancer, as mentioned in some presentations at the 2024 CSCO Gynecological Cancer session. The U.S. has approved an FRα-targeting ADC called mirvetuximab soravtansine (MIRV) for ovarian cancer, which has shown significant benefits for platinum-resistant ovarian cancer patients. At the 2024 ESMO Congress, the PICCOLO trial reported that MIRV also had promising results in recurrent platinum-sensitive ovarian cancer patients with high FRα expression, with at least half of the treated patients responding to MIRV monotherapy. MIRV has paved the way for further development of FRα-targeted ADCs in ovarian cancer. Other FRα-targeted ADCs and ADCs targeting different antigens are also under development. For example, an ADC targeting HER2 has been approved in the U.S. for ovarian and cervical cancer. Clinicians now need pathologists to tell us whether HER2 expression is high enough in ovarian cancer patients to make this drug a viable treatment option.
The field of precision diagnosis has advanced tremendously, and Professor Rao knows this better than I do, as he’s been developing many of these technologies. We need to start integrating these large data sets, using AI to analyze data like mutations, epigenetic modifications, and protein expression to create algorithms that are more predictive of treatment outcomes. This goal will be achieved, though it will take some years. But we already have the tools to get there.
Again, the progress in precision cancer diagnosis is exciting. It’s complex, but let’s see where it leads us. Ultimately, it’s all about benefiting the patients. It’s important to select patients who are likely to respond to a treatment, but it’s equally important to exclude those who would experience only side effects with no therapeutic benefit.
5. Could you briefly describe the work you’re doing in the ovarian cancer field and the research you’re currently conducting?
Dr. Jianyu Rao: Dr. Dorigo has already touched on my focus. Currently, there are many new technologies, tools, and products emerging in cancer diagnosis, and integration is the key. The most critical issue for the future is finding the best way to integrate these effective technologies to provide clinicians with more precise diagnostic information, ultimately aiding patient care. For example, pathological diagnosis may need to incorporate radiographic imaging, histological morphology, molecular changes, and proteogenomics data. We can rely on AI and machine learning for integration. Integrating all these diagnostic techniques to develop a “smart diagnosis” system is what we’re currently researching.
Dr. Lingying Wu: Integrating existing diagnostic techniques into a smart diagnostic system would have clinical significance for early tumor detection, precision treatment, and early recurrence diagnosis. This is also our vision, and I hope we can collaborate with Professor Rao in the future. Our team has conducted extensive clinical and translational research on refractory ovarian cancer, such as platinum-resistant and HRP patients, to identify treatment strategies that can improve five-year survival. This includes research on novel ADC drugs and various drug combination therapies.
Dr. Oliver Dorigo: I’ve been involved in developing immunotherapies for ovarian cancer for a long time, starting with vaccines, with 15 years of research behind me. Recently, I’ve been excited about an intraperitoneal CAR-T cell therapy that targets a protein called B7-H3, which is highly expressed in ovarian cancer. In a few weeks, we will begin treating our first patients, and I hope to return to CSCO in the future to share some results.
Dr. Lingying Wu
Chief Physician, Doctoral Supervisor Tenured Professor at Peking Union Medical College Vice President of Liaoning Hospital of the Cancer Hospital, Chinese Academy of Medical Sciences Vice President of CSCO Chairman of the CSCO Gynecologic Oncology Expert Committee Chairman of the Minimally Invasive Professional Committee of the Chinese Maternal and Child Health Association Vice Chairman of the National Anti-Cancer Drug Clinical Application Monitoring Committee Vice Chairman of the CSCO Clinical Research Expert Committee Executive Director of the Chinese Maternal and Child Health Association
Dr. Oliver Dorigo
Director of the Division of Gynecologic Oncology, Stanford University, and Associate Professor Research Interests: Applications of immunotherapy, particularly developing vaccines and cellular therapies for ovarian cancer His research has been published in Journal of Virology, Proceedings of the National Academy of Sciences, Journal of Immunology, and Cancer Gene Therapy.
Dr. Jianyu Rao
Jianyu Rao, MD, FAcadTM Tenured Professor of Pathology and Epidemiology, UCLA Director of Cytopathology at UCLA, former Director of the Division of Gynecologic Pathology, Director of International Telepathology, and Medical Director of the School of Cytotechnology Renowned expert in cancer biomarkers and prevention research, molecular cytopathology, pathology of urologic and gynecologic cancers, digital pathology, and cancer nanomechanics research His notable achievements include establishing the first international telepathology program for second-opinion consultations and studying actin cytoskeleton remodeling in cancer development and progression, as well as researching cellular nanomechanical analysis as a cancer biomarker.
