Dr Graham on Advancements in the Management of Ovarian Cancer

"Relatively recent data suggest that neoadjuvant therapy is as good as adjuvant therapy, so we are giving a bit more neoadjuvant chemotherapy. Now that we have those data, it’s important for our patients because it leads to equal outcomes. We can consider not just aspects of… the tumor, but also what’s going on with the patient."

Deena M. Atieh Graham, MD, medical oncologist at John Theurer Cancer Center at Hackensack Meridian Health, discussed recent treatment developments and the current therapeutic landscape for patients with advanced ovarian cancer.

The majority of patients with ovarian cancer continue to present with stage III or IV disease, which underscores the need for effective systemic strategies, Graham began. Recent data suggest that neoadjuvant chemotherapy offers outcomes comparable to primary cytoreductive surgery, leading to increased use of this approach, particularly for patients who may not be optimal surgical candidates at presentation. This shift allows oncologists to consider not only tumor burden and resectability but also patient-specific factors, such as overall health and surgical fitness, when determining initial management strategies, Graham explained.

Another key area of evolution is the use of maintenance therapy following initial treatment. In patients with 

 wild-type tumors who are also homologous recombination deficiency (HRD) negative based on germline or somatic testing, maintenance therapy with bevacizumab (Avastin) remains a commonly used option. This approach is generally reserved for patients who are less likely to derive benefit from receiving PARP inhibitors, Graham noted.

-mutated disease, the use of maintenance PARP inhibitors has become a standard of care and is now widely integrated into frontline disease management. These therapies have been shown to prolong progression-free survival, reinforcing their value in biomarker-selected populations. The broader use of PARP inhibitors has fundamentally changed the treatment paradigm for 

-mutated ovarian cancer and has highlighted the importance of timely and comprehensive biomarker testing early in the disease course, Graham concluded.

Videos

Deena M. Atieh Graham, MD, discusses notable shifts within the ovarian cancer landscape leading to better patient outcomes. 

Deena M. Atieh Graham, MD, medical oncologist at John Theurer Cancer Center at Hackensack Meridian Health, discussed the FDA approval of mirvetuximab soravtansine-gynx (Elahere) following World Ovarian Cancer Day. 

Dr Graham on the Significance of the FDA Approval of Mirvetuximab Soravtansine in Ovarian Cancer 

“Antibody-drug conjugates [ADCs] are here to stay [in ovarian cancer]. In other tumor types such as breast cancer, we’ve learned that it’s not just about the target; an ADC is made up of the linker, the payload, and the target. There are always ways to manipulate those 3 [elements]. Those of us who [treat] patients with ovarian cancer need to understand more about these tumors [in order to create] more targeted therapies.”

Deena M. Atieh Graham, MD, medical oncologist at John Theurer Cancer Center at Hackensack Meridian Health, discussed the FDA approval of mirvetuximab soravtansine-gynx (Elahere) following 

In March 2024, the FDA granted regular approval to mirvetuximab soravtansine

 for the treatment of patients with folate receptor α (FRα)–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have previously received 1 to 3 systemic therapy regimens. The approval was supported by data from the phase 3 MIRASOL trial (NCT04209855). Patients who received mirvetuximab soravtansine (n = 227) experienced a median overall survival of 16.5 months (95% CI, 14.5-24.6) vs 12.7 months (95% CI, 10.9-14.4) for patients who received investigator’s choice of chemotherapy (n = 226; HR, 0.67; 95% CI, 0.50-0.88; 

The development and approval of mirvetuximab soravtansine underscores the shift towards targeted therapies in ovarian cancer, which now also include HER2-directed agents, Graham said. In the past, most patients with ovarian cancer were treated in a similar manner, but now with the emergence of more targeted agents, oncologists can use personalized medicine to a greater degree, she continued. There is also interest among investigators in moving targeted treatments into the maintenance setting of ovarian cancer, Graham noted.

Mirvetuximab soravtansine is currently being evaluated in combination with bevacizumab (Avastin) in the maintenance setting in the phase 3 GLORIOSA study (NCT05445778). GLORIOSA is enrolling patients with FRα-high ovarian cancer who did not experience disease progression after second-line treatment with platinum-based doublet chemotherapy and bevacizumab. Patients will be randomly assigned 1:1 to receive mirvetuximab soravtansine plus bevacizumab or bevacizumab monotherapy.

Deena M. Atieh Graham, MD, discusses the FDA approval of mirvetuximab soravtansine.

Deena M. Atieh Graham, MD, medical oncologist at John Theurer Cancer Center at Hackensack Meridian Health, discussed ongoing studies of note in patients with ovarian cancer following World Ovarian Cancer Day.

Dr Graham on Notable Ongoing Studies in Ovarian Cancer

"The future [of ovarian cancer treatment] is an individualized approach to [treating] each patient. This will be the key to identifying the treatments that work and minimizing toxicities or exposure to medications that may not work.”

Deena M. Atieh Graham, MD, medical oncologist at John Theurer Cancer Center at Hackensack Meridian Health, discussed ongoing studies of note in patients with ovarian cancer following 

2025 SGO Annual Meeting on Women’s Cancer

, investigators presented data from part 1b of the ongoing phase 2 DENALI trial (NCT05128825) which is examining the WEE1 inhibitor azenosertib in patients with platinum-resistant ovarian cancer, Graham explained. At the January 13, 2025, data cutoff, response-evaluable patients with cyclin E1–positive disease (n = 43) achieved an objective response rate (ORR) of 34.9% (95% CI, 21.0%-50.9%). Patients in the intention-to-treat population with cyclin E1–positive disease (n = 48) experienced an ORR of 31.3% (95% CI, 18.7%- 46.3%) and a median duration of response of 6.3 months (95% CI, 2.7-not estimable).

Graham also noted that investigators are anticipating the results of the ongoing phase 3 GLORIOSA study (NCT05445778). GLORIOSA is examining the antibody-drug conjugate (ADC) mirvetuximab soravtansine-gynx (Elahere) in combination with bevacizumab (Avastin) vs bevacizumab monotherapy as maintenance therapy in patients with folate receptor α (FRα)–high ovarian cancer who did not experience disease progression following second-line treatment withplatinum-based doublet chemotherapy plus bevacizumab, she added. The primary end point of the study is investigator-assessed progression-free survival (PFS).

In March 2024, the FDA granted full approval to mirvetuximab soravtansine

 for the treatment of patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have previously received 1 to 3 systemic therapy regimens. The regulatory decision was supported by findings from the phase 3 MIRASOL trial (NCT04209855), which demonstrated that patients who received the ADC (n = 227) achieved a median overall survival of 16.5 months (95% CI, 14.5-24.6) compared with 12.7 months (95% CI, 10.9-14.4) among patients treated with investigator’s choice of chemotherapy (n = 226; HR, 0.67; 95% CI, 0.50-0.88; 

 = .0046). The median PFS was 5.6 months (95% CI, 4.3-5.9) vs 4.0 months (95% CI, 2.9-4.5), respectively (HR, 0.65; 95% CI, 0.52-0.81; 

Deena M. Atieh Graham, MD, discusses ongoing studies of note in patients with ovarian cancer following World Ovarian Cancer Day.

Dr Graham on the Evaluation of RAGE Inhibition for Therapy-Related Cardiotoxicity in Breast Cancer

Deena Mary Atieh Graham, MD, gynecologic medical oncology, breast medical oncologist, John Theurer Cancer Center, Hackensack University Medical Center, discusses the rationale and objectives of a phase 1/2 pilot study (NCT05256745) evaluating RAGE inhibition to reduce cancer therapy–related cardiotoxicity in women with early-stage breast cancer.

Graham explains that this study aims to investigate the potential role the RAGE inhibitor azeliragon in mitigating long-term cardiac toxicity associated with certain chemotherapeutic regimens for patients with breast cancer. Although providing patients with effective cancer treatment remains a crucial goal, promoting long-term quality of life and survivorship is important for patients with breast cancer, she explains.

Graham and colleagues presented a posted on this trial in progress at the 

. The primary objectives of the study are to assess changes in high-sensitivity troponin levels—a biomarker for cardiac injury—before and during treatment with azeliragon, and to evaluate the safety and tolerability of this agent when given with standard chemotherapy. Pharmacokinetics and bioavailability of the chemotherapeutic agents in combination with the RAGE inhibitor are also being analyzed.

Investigators aim to enroll 24 patients, and 8 had already been enrolled as of the May 20, 2024. Seven patients had completed treatment, two were actively receiving treatment, and one was in screening.

Graham explains that chemotherapy regimens administered to patients in the study were selected by the patients’ oncologists, and they included commonly used protocols such as doxorubicin plus cyclophosphamide, docetaxel in combination with carboplatin, trastuzumab (Herceptin), and pertuzumab (Perjeta), and docetaxel plus cyclophosphamide. Some patients also received dose-dense paclitaxel.

The RAGE inhibitor is being administered during later chemotherapy cycles, and patients are then monitored closely, Graham continues. The primary hope for this study is that RAGE inhibition will prove to be a safe strategy that does not alter the bioavailability of the chemotherapeutic agents, thereby setting the foundation for future research into cardioprotective strategies in breast cancer treatment, Graham concludes.

Deena Mary Atieh Graham, MD, discusses a pilot study evaluating RAGE inhibition to reduce therapy-related cardiotoxicity in early-stage breast cancer.

Deena Mary Atieh Graham, MD

Articles

Dr Graham on Advancements in the Management of Ovarian Cancer

Dr Graham on the Significance of the FDA Approval of Mirvetuximab Soravtansine in Ovarian Cancer

Dr Graham on Notable Ongoing Studies in Ovarian Cancer

Dr Graham on the Evaluation of RAGE Inhibition for Therapy-Related Cardiotoxicity in Breast Cancer