Dr Crafton on the Use of Mirvetuximab Soravtansine in Ovarian Cancer

Sarah Crafton, MD, gynecologic oncologist, Allegheny Health Network, discusses the potential future of antibody-drug conjugates (ADCs) in patients with ovarian cancer.

ADCs are a unique, novel class of cancer therapy that has had notable success in ovarian cancer, Crafton begins. In 2022, 

the FDA approved the ADC mirvetuximab soravtansine

-gynx (Elahere) for the treatment of patients with folate receptor α (FRα)–positive, platinum-resistant ovarian cancer. The positive data from the pivotal phase 3 SORAYA trial (NCT04296890) indicates that ADCs will continue to be developed to treat patients with this disease, Crafton emphasizes.

HER2-directed ADCs have the potential to change clinical practice for patients with ovarian cancer, Crafton says. Although more ovarian cancer–specific data with ADCs need to be generated, interim results from the phase 2 DESTINY-PanTumor02 trial (NCT04482309), 

which were presented at the 2023 ASCO Annual Meeting

, have sparked excitement across oncology, Crafton explains. This trial evaluated the safety and efficacy of the HER2-directed ADC fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with a variety of HER2-expressing solid tumors.

In the population of patients with ovarian cancer (n = 40), the overall response rate (ORR) was 45.0%, including complete response, partial response, stable disease, and progressive disease rates of 10.0%, 35.0%, 35.0%, and 17.5%, respectively (1 patient was not evaluable). The ORR per independent central review was 42.5%. The 12-week disease control rate was 70.0%, and the median duration of response was 11.3 months (95% CI, 4.1-not evaluable). Although the number of patients with gynecologic cancers enrolled in DESTINY-PanTumor02 was relatively small, these early findings validate the ongoing further research with HER2 as a biomarker in this patient population, Crafton emphasizes.

FRα is another common target for ADCs in ovarian cancer, Crafton notes, adding that additional ovarian cancer clinical trials are investigating TROP2 as another potential target for ADCs in this patient population. Many of the ADCs targeting FRα and TROP2 are still in early development, but they will be important to watch for in the future, Crafton notes.

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Sarah Crafton, MD, discusses the potential future of antibody-drug conjugates in patients with ovarian cancer.

Dr Crafton on the Impact of Mirvetuximab Soravtansine on Clinical Practice in Ovarian Cancer

Sarah Crafton, MD, gynecologic oncologist, Allegheny Health Network, discusses the integration of mirvetuximab soravtansine-gynx (Elahere) into clinical practice in the treatment of ovarian cancer, highlighting how the agent has bolstered interest in evaluating other antibody-drug conjugates (ADCs) in earlier settings.

ADCs represent a promising class of anti-cancer therapies with notable success in ovarian cancer, Crafton begins. This is exemplified by the FDA's 

accelerated approval of mirvetuximab soravtansine

 for pretreated adult patients with folate receptor α (Frα)–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer in November 2022.

The regulatory decision was based on findings from the phase 3 MIRASOL trial (NCT04209855), in which progression-free survival, objective response rates, and overall survival was increased with the ADC compared with single-agent chemotherapy.

The Allegheny Health Network has since participated in several clinical trials evaluating mirvetuximab soravtansine, assisting in the familiarization with the agent before its widespread adoption, Crafton says. As a result, the integration of mirvetuximab soravtansine into clinical practice has been relatively seamless, she asserts. The integration of this agent is supported by established infrastructure and close collaboration with ophthalmologists to manage ocular toxicities associated with this medication, Crafton adds.

Although mirvetuximab soravtansine is currently available for use in the platinum-resistant setting, ongoing trials are exploring its potential use in earlier lines of treatment, Crafton continues. The phase 3 GLORIOSA trial (NCT05445778) is investigating mirvetuximab soravtansine with or without bevacizumab (Avastin) as maintenance therapy in patients with platinum-sensitive disease, offering insights into expanded treatment options, Crafton states. The trial is ongoing and recruiting patients. Additionally, a phase 2 investigator-initiated trial (NCT04606914) at the University of Alabama Birmingham is assessing mirvetuximab soravtansine with carboplatin in the neoadjuvant setting, Crafton details.

These ongoing trials hold promise in advancing the use of mirvetuximab soravtansine for patients with ovarian cancer, potentially expanding its therapeutic benefits to patients in earlier stages of the disease, she states. Investigators remain optimistic about the prospects of integrating this novel ADC into various treatment paradigms to improve outcomes for patients with ovarian cancer, Crafton concludes.

Sarah Crafton, MD, discusses the integration of mirvetuximab soravtansine-gynx  into clinical practice in the treatment of ovarian cancer.

Dr Crafton on Emerging Therapeutic Targets in Ovarian Cancer

Sarah Crafton, MD, gynecologic oncologist, Allegheny Health Network, discusses novel therapeutic targets under investigation in patients with ovarian cancer.

The phase 2 innovaTV 208 trial (NCT03657043) is investigating the tissue factor–directed antibody-drug conjugate (ADC) tisotumab vedotin-tftv (Tivdak) in patients with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer. This trial is evaluating the ADC in a safety run-in portion, as well as in 3 study groups. Group 1 (part A) will receive the agent once every 3 weeks. Groups 2 (part A) and 3 (part B) will receive the ADC once weekly for 3 weeks on followed by 1 week off. The safety run-in portion of the trial is evaluating the number of patients with dose-limiting toxicities. The primary end point of part B is confirmed overall response rate (ORR). Secondary end points in part B include the number of patients with adverse effects, CA-125 response rate, duration of response (DOR), disease control rate, time to response, progression-free survival (PFS), and overall survival (OS). The final publication of findings from this trial is pending, and these data may influence future clinical practice, Crafton says. 

HER2 is another emerging target in ovarian cancer research, having gained prominence as an important prognostic biomarker in several cancers, Crafton explains. For instance, the phase 2 DESTINY-PanTumor02 trial (NCT04482309) is investigating the efficacy and safety of the ADC fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with HER2-expressing cancers, such as ovarian, endometrial, cervical, biliary tract, bladder, and pancreatic cancers. At a median follow-up of 12.75 months, the ORR in the overall study population was 37.1% (95% CI, 31.3%-43.2%), and responses were observed in all patient cohorts. Furthermore, the median DOR was 11.3 months (95% CI, 9.6-17.8), and the median PFS and OS were 6.9 months (95% CI, 5.6-8.0) and 13.4 months (95% CI, 11.9-15.5), respectively.

HER2-targeted ADCs can produce greater efficacy than monoclonal antibodies, such as trastuzumab (Herceptin), according to Crafton. The development of HER2-directed ADCs will continue in ovarian cancer and other cancers, Crafton concludes.

Sarah Crafton, MD, discusses novel therapeutic targets under investigation in patients with ovarian cancer.

Sarah Crafton, MD, gynecologic oncologist, Allegheny Health Network, discusses the personalized choice of undergoing secondary cytoreduction for patients with ovarian cancer.

Assessing the role of secondary cytoreduction has to be a personalized choice based on objective data from studies as well as patient preference, explains Crafton. Typically, these patients previously would undergo a primary cytoreductive surgery that may either influence them positively or negatively about aspiring to a second surgery, says Crafton. Therefore, a personalized conversation with the patient should take place.

The randomized phase III AGO DESKTOP III/ENGOT ov20 trial found a clinically meaningful progression-free survival (PFS) and time to first subsequent therapy (TFST) improvement with surgery over second-line chemotherapy in patients with first-relapse, AGO-positive ovarian cancer who had a platinum-free interval of ≥6 months. The median PFS was 19.6 months compared with 14.0 months (HR, 0.66; 95% CI, 0.52-0.83; 

 <.001), and median TFST was 21.0 months versus 13.9 months (HR, 0.61; 95% CI, 0.48-0.77; 

 <.001), showing results in favor of surgery. Data from this trial provide some criteria that can be used to direct counseling and patient selection for secondary cytoreduction, concludes Crafton.

Sarah Crafton, MD, discusses the personalized choice of undergoing secondary cytoreduction for patients with ovarian cancer.

Dr. Crafton on Considerations for Secondary Cytoreduction in Ovarian Cancer

Sarah Crafton, MD, gynecologic oncologist, Allegheny Health Network, discusses the impact of PARP inhibitors on patients with recurrent ovarian cancer.

PARP inhibitors have transformed the recurrent ovarian cancer setting because as a novel agent in terms of its basic science, mechanism, and application, it also allows patients to take it orally in pill form versus intravenous chemotherapy, explains Crafton. Many patients feel liberated by this change in delivery, although they still need to visit their physician regularly, have their symptoms monitored, and receive regular lab evaluation, says Crafton.

 mutation or have homologous recombination deficiency, PARP inhibitors have revolutionized care for recurrent ovarian cancer by increasing the amount of time between systemic chemotherapy treatments, concludes Crafton.

Sarah Crafton, MD, discusses the impact of PARP inhibitors on patients with recurrent ovarian cancer.

Dr. Crafton on the Impact of PARP Inhibitors in Recurrent Ovarian Cancer

Sarah Crafton, MD, gynecologic oncologist, Allegheny Health Network, discusses secondary surgical cytoreduction in recurrent ovarian cancer.

Two large, randomized, controlled trials evaluated the role of surgical cytoreduction in recurrent ovarian cancer, says Crafton. However, the trials have conflicting results. The phase III AGO DESKTOP III/ENGOT ov20 trial demonstrated that patients who have a good performance status, low-volume ascites, and had an optimal initial primary cytoreduction could be good candidates for secondary surgery. Notably, data from the trial demonstrated a progression-free survival (PFS) benefit with secondary cytoreductive surgery.

However, data from the phase III GOG-0213 trial that was recently published in 

 showed no PFS or overall survival advantage in patients who had surgery and chemotherapy versus chemotherapy alone.

Dr. Crafton on Secondary Surgical Cytoreduction in Ovarian Cancer

Sarah Crafton, MD, gynecologic oncologist, Allegheny Health Network, discusses optimizing treatment selection in recurrent ovarian cancer.

Platinum-sensitivity should be used to guide treatment selection in the recurrent setting, says Crafton. Notably, a variety of platinum-based therapies and targeted therapies are available to patients with platinum-sensitive disease. and platinum-resistant disease.

The National Comprehensive Cancer Network publishes a list of available agents for patients with platinum-sensitive and platinum-resistant disease. The decision of which treatment to pursue should be based on previous toxicities, disease-related symptoms, prior platinum status, and current functional status, concludes Crafton.