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What’s the Latest in Ovarian
Cancer?
Report Back from SGO 2024
May 1, 2024
Elena Pereira, MD
Assistant Professor
Division of Gynecologic Oncology
Lenox Hill Hospital, NY
Ovarian Cancer
• Ovarian and Fallopian Tube cancers are the second
most common gynecologic malignancy, with an
incidence of 26,000 annually (1 in 70 women.)
• Epithelial ovarian are the most common subtype of
ovarian cancer and constitute approximately 90% of
the malignant ovarian neoplasms.
• Ovarian and Fallopian Tube cancers spread along the
surfaces of the abdominal cavity and implant on
organs like the small and large intestines.
Management of Ovarian Cancer
Adjuvant
Chemotherapy
PRIMARY CYTOREDUCTION
Neoadjuvant
Chemotherapy
DIAGNOSTIC LAPAROSCOPY
INTERVAL DEBULKING
Chemo
New
Diagnosis
Resectable Disease
Unresectable Disease
Indeterminate
BIOPSY
Recurrence
Chemotherapy
Targeted Tx
Surgery
Chemotherapy
• The combination of carboplatin and paclitaxel is the currently the standard
backbone of treatment.
• 70% of women with advanced ovarian cancer will achieve complete clinical
remission after initial surgery and platinum-based chemotherapy.
• For patients with certain inherited mutations targeted therapies, such as
PARP inhibitors can significantly improve outcomes.
Cell Cycle
Cancers 2021, 13(6), 1298; https://doi.org/10.3390/cancers13061298
Bevacizumab
• Binds to circulating vascular endothelial growth factor (VEGF)
interfering with endothelial cell proliferation and blocking
angiogenesis
PARP Inhibitors
Cancers 2023, 15(14), 3642; https://doi.org/10.3390/cancers15143642
FRONT LINE TREATMENT
Cancers 2021, 13(6), 1298; https://doi.org/10.3390/cancers13061298
Treatment of Recurrence
Cancers 2021, 13(6), 1298; https://doi.org/10.3390/cancers13061298
Understanding Clinical Trials
• Progression Free Survival
• Time from completion of treatment to recurrence
• Can be expressed in months as median progression free survival (time that it
takes 50% of patients to recur) OR as a percentage of patients who have not
recurred at a specific time point.
• Overall Survival
• Time from completion of treatment to death from disease.
• Can be expressed in months as median overall free survival (time that it takes
50% of patients to die from disease) OR as a percentage of patients who have not
died at a specific time point.
• Hazard Ratio
• Expressed as a decimal and gives an indication of how much better or worse the
experimental arm is.
• Example: a HR of 0.60 means that patients on the experimental drug are 40%
less likely to have their cancer return. A HR of 1.4 would mean that a patient is
40% more likely to have their cancer return with the experimental drug.
Interim Post-Progression Data and Updated Survival in Patients with Newly Diagnosed
Advanced Ovarian Cancer in ATHENA-MONO
BRCA +
BRCA-
JCO
June 2022
Mirvetuximab Soravtansine
Mirvetuximab Soravtansine: Side Effects
• Eye problems: eye problems are common and can also be severe
including blurred vision, dry eyes, sensitivity to light, eye pain, eye
redness, or new or worsening vision changes.
• Lung problems (pneumonitis): can cause severe or life-threatening
inflammation of the lungs that may lead to death. Tell your healthcare
provider right away if you get new or worsening symptoms, including
trouble breathing, shortness of breath, cough, or chest pain.
• Peripheral neuropathy: peripheral neuropathy is common during
treatment and can also be severe. Your healthcare provider will monitor
you for signs and symptoms of nerve problems. Tell your healthcare
provider if you get new or worsening numbness, tingling, burning
sensation or pain in your hands or feet or muscle weakness.
Conclusions
• R-Dxd is the first CDH6-directed ADC to demonstrate promising efficacy in
heavily pretreated patient with ovarian cancer.
• Efficacy does not seem to be dependent on the level of CDH6 expressed by
the cancer cells.
• ORR was 48.6 %, including 1 complete response and 17 partial responses.
• Median duration of response was 11.2 months
• Median progression free survival was 8.1 months
• Toxicities appear to be manageable.
• Phase 2/3 has been initiated globally- REJOICE OVARY 01
Summary
• PARP Inhibitors continue to show the most profound improvement in
outcomes for patients with ovarian cancer (most significantly in patients with
BRCA mutation)
• Bevacizumab remains an important targeted therapy, especially in the
maintenance and platinum resistant setting.
• Mirvetuximab-Soravtansine: improves PFS and OS when compared to single-
agent chemotherapy in patients with platinum resistant ovarian cancer.
• R-DXd demonstrates promising efficacy in heavily pretreated patients, and is
moving to Phase 2/3 development- REJOICE-Ovarian01 Trial.
• We continue to explore the potential role of immunotherapy in ovarian
cancers.
Thank you!

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Report Back from SGO: What’s the Latest in Ovarian Cancer?

  • 1. What’s the Latest in Ovarian Cancer? Report Back from SGO 2024 May 1, 2024 Elena Pereira, MD Assistant Professor Division of Gynecologic Oncology Lenox Hill Hospital, NY
  • 2. Ovarian Cancer • Ovarian and Fallopian Tube cancers are the second most common gynecologic malignancy, with an incidence of 26,000 annually (1 in 70 women.) • Epithelial ovarian are the most common subtype of ovarian cancer and constitute approximately 90% of the malignant ovarian neoplasms. • Ovarian and Fallopian Tube cancers spread along the surfaces of the abdominal cavity and implant on organs like the small and large intestines.
  • 3. Management of Ovarian Cancer Adjuvant Chemotherapy PRIMARY CYTOREDUCTION Neoadjuvant Chemotherapy DIAGNOSTIC LAPAROSCOPY INTERVAL DEBULKING Chemo New Diagnosis Resectable Disease Unresectable Disease Indeterminate BIOPSY Recurrence Chemotherapy Targeted Tx Surgery
  • 4. Chemotherapy • The combination of carboplatin and paclitaxel is the currently the standard backbone of treatment. • 70% of women with advanced ovarian cancer will achieve complete clinical remission after initial surgery and platinum-based chemotherapy. • For patients with certain inherited mutations targeted therapies, such as PARP inhibitors can significantly improve outcomes.
  • 6. Cancers 2021, 13(6), 1298; https://doi.org/10.3390/cancers13061298
  • 7. Bevacizumab • Binds to circulating vascular endothelial growth factor (VEGF) interfering with endothelial cell proliferation and blocking angiogenesis
  • 8. PARP Inhibitors Cancers 2023, 15(14), 3642; https://doi.org/10.3390/cancers15143642
  • 9. FRONT LINE TREATMENT Cancers 2021, 13(6), 1298; https://doi.org/10.3390/cancers13061298
  • 10. Treatment of Recurrence Cancers 2021, 13(6), 1298; https://doi.org/10.3390/cancers13061298
  • 11. Understanding Clinical Trials • Progression Free Survival • Time from completion of treatment to recurrence • Can be expressed in months as median progression free survival (time that it takes 50% of patients to recur) OR as a percentage of patients who have not recurred at a specific time point. • Overall Survival • Time from completion of treatment to death from disease. • Can be expressed in months as median overall free survival (time that it takes 50% of patients to die from disease) OR as a percentage of patients who have not died at a specific time point. • Hazard Ratio • Expressed as a decimal and gives an indication of how much better or worse the experimental arm is. • Example: a HR of 0.60 means that patients on the experimental drug are 40% less likely to have their cancer return. A HR of 1.4 would mean that a patient is 40% more likely to have their cancer return with the experimental drug.
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  • 13. Interim Post-Progression Data and Updated Survival in Patients with Newly Diagnosed Advanced Ovarian Cancer in ATHENA-MONO
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  • 27. Mirvetuximab Soravtansine: Side Effects • Eye problems: eye problems are common and can also be severe including blurred vision, dry eyes, sensitivity to light, eye pain, eye redness, or new or worsening vision changes. • Lung problems (pneumonitis): can cause severe or life-threatening inflammation of the lungs that may lead to death. Tell your healthcare provider right away if you get new or worsening symptoms, including trouble breathing, shortness of breath, cough, or chest pain. • Peripheral neuropathy: peripheral neuropathy is common during treatment and can also be severe. Your healthcare provider will monitor you for signs and symptoms of nerve problems. Tell your healthcare provider if you get new or worsening numbness, tingling, burning sensation or pain in your hands or feet or muscle weakness.
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  • 33. Conclusions • R-Dxd is the first CDH6-directed ADC to demonstrate promising efficacy in heavily pretreated patient with ovarian cancer. • Efficacy does not seem to be dependent on the level of CDH6 expressed by the cancer cells. • ORR was 48.6 %, including 1 complete response and 17 partial responses. • Median duration of response was 11.2 months • Median progression free survival was 8.1 months • Toxicities appear to be manageable. • Phase 2/3 has been initiated globally- REJOICE OVARY 01
  • 34.
  • 35. Summary • PARP Inhibitors continue to show the most profound improvement in outcomes for patients with ovarian cancer (most significantly in patients with BRCA mutation) • Bevacizumab remains an important targeted therapy, especially in the maintenance and platinum resistant setting. • Mirvetuximab-Soravtansine: improves PFS and OS when compared to single- agent chemotherapy in patients with platinum resistant ovarian cancer. • R-DXd demonstrates promising efficacy in heavily pretreated patients, and is moving to Phase 2/3 development- REJOICE-Ovarian01 Trial. • We continue to explore the potential role of immunotherapy in ovarian cancers.

Editor's Notes

  1. For many women, the cancer will stay confined to the peritoneal cavity throughout the disease course
  2. An extensive body of retrospectively and prospectively acquired data has demonstrated that removal of all implants larger than 1 to 2 cm is associated with a dramatically increased survival.[10] This has been demonstrated even in patients with stage IV disease.
  3. The cell cycle is represented here. Rapidly dividing cells, such as cancer, are constantly in the active phase of the cell cycle while many of our normal cells are at rest and in the G0 phase. Chemotherapy targets these rapidly dividing cells by acting on different parts of the cell cycle. The idea is that the cancer cells are more sensitive to the chemotherapy and our normal cells are less sensitive. However, our bodies also have normal cells in the active phase of the cell cycle, such as our hair and bone marrow. This is what leads to the side effects of chemotherapy. The reason I wanted to spend a few minutes on this is because I think it is important to understand what makes our newer “targeted” treatments different from chemotherapy.
  4. Chemotherapy was all we had for a long time. It wasn’t until 2011 that we started adding these more targeted treatments to the carboplatin/paclitaxel backbone. This is a busy slide that highlights just how many studies and FDA approvals there were over that subsequent decade. The take away is that in the 10 years represented here, the two major advances were in the addition of bevacizumab and PARP inhibitors to the carbo/taxol backbone, which remains the standard of treatment.
  5. Fast growing tumors quickly outgrow their blood supply and in response to an overall hypoxic state, mechanisms are initiated for recruitment of blood vessels (angiogenesis). Avastin blocks this mechanism.
  6. PARP inhibitors are another interesting targeted therapy. For some patients, ovarian cancer development is driven by certain gene mutations commonly referred to as BRCA mutations, but also referred to as HRD mutations in the literature. Basically cells have several ways of repairing the mistakes in DNA that can occur during cell division. BRCA mutated genes are missing one of these mechanisms, so they rely on the PARP pathway to repair DNA. If you use a PARP inhibitor to also block that DNA repair mechanism, the DNA cannot be repaired and the cancer cell cannot survive. This is considered targeted therapy because all of the other cells in this patient’s body have normally functioning BRCA genes so they can repair themselves via the BRCA pathway and are not affected by the PARP inhibitor.
  7. Another important trial that belongs here is the Athena trial, which looked at the PARP inhibitor rucaparib in the upfront setting. New data from that trial was presented this year at SGO so I will discuss that one in more detail in a few slides.
  8. I just want to spend a few minutes on how we, as the gyn oncologists, review these studies and how we determine which new treatments could be beneficial to our patients.
  9. This year’s Society of Gynecologic Oncology meeting was in San Diego. My goal today was to really bring you the highlights in ovarian cancer from this year’s meeting.
  10. This is another PARP inhibitor trial for maintenance in the upfront setting. That means the patient is given standard carbo/taxol and is continued on the PARP inhibitor for up to 2 years. All patients included regardless of HRD status. Of note, this study also included nivolumab, an immunotherapy agent. The MONO study (which only had the PARP inhibitor) and the COMBO study (which included both the PARP and the immunotherapy) were calculated separately and the results reported separately. The COMBO data is not mature yet.
  11. The conclusion from this preliminary data was that Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.
  12. From this the Authors Conclusions • With 3 years of follow-up, ATHENA-MONO TFST and PFS2 interim data suggest that rucaparib benefit continues beyond completion of treatment and first progression • Analyses of TFST and PFS2 suggested there was greater clinical benefit with rucaparib versus placebo for the HRD and ITT populations • The second interim analysis of OS at 35% maturity for ITT showed hazard ratio <1 in the HRD (25% maturity) and ITT populations favoring rucaparib • Estimated median OS was not reached at the time of data cutoff, except for the placebo arm of the ITT group
  13. Mirvetuximab soravtansine-gynx (Elahere) is an antibody-drug conjugate (ADC) that targets folate receptor alpha (FRα). FRα is highly expressed in epithelial ovarian cancer (EOC), making it a promising target for treating this disease. The folate receptor doesn’t drive the cancer growth, and therefore it is not itself a target, but it is something that these drugs can latch onto in order to get into the cancer cells.
  14. People treated with ELAHERE can develop eye-related side effects, which can be severe. These may include blurred vision, dry eyes, sensitivity to light, eye pain, eye redness, or new or worsening vision changes. Tell your doctor if you have a history of vision or eye problems. Avoid wearing contact lenses throughout your treatment with ELAHERE unless your doctor tells you that you can. Your doctor will also have you meet with an eye doctor (optometrist or ophthalmologist) before your first infusion and periodically throughout your treatment. You will receive instructions for eye drops to use during your treatment. Be sure to use them as directed. Explore the Eye Drop Tracker While on treatment, use this tool to help track your eye drop use, notes to share with your doctor, and upcoming appointments 1% of people in the study stopped treatment because of eye problems
  15. This is another antibody drug conjugate.
  16. REJOICE is currently open in Japan, but has been assigned a GOG trial number so hopefully that means it will open in the US soon.