Lec 5: Ovarian Cancer Flashcards
Background on ovarian cancer …types and goal of therapy
Types:
- Epithelial (90%) - what we will be focusing on !
- Germ cell
- Stromal carcinomas
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Goal of therapy:
- Stage I-II: Cure
- Stage III-IV: Cure (but not always possible with unresectable or stage IV disease)
Molecular testing
Ideal to pursue during the start of initial therapy to help direct subsequent therapy options!
- Germline +/- somatic BRCA1/2 evaluation
- Homologous recombination deficiency (HRD)
- Patients with BRCA1/2 mutation will have HRD
…… However, about a third of patient will not have BRCA1/2 mutation but with have HRD which adds some treatment options
Initial Therapy options: Localization options
Initial Therapy options: Role of neoadjuvant therapy
- Only considered for bulky stage III-IV disease who are unlike to be optimally cytoreduced (<1 cm) and/or poor surgical candidate
- After neoadjuvant therapy, the surgeon reassesses the ability to achieve optimal cytoreduction with imaging and determines plan for surgery
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Options: - Any of the IV chemo regimens used in Stage II-IV disease (does not include intraperitoneal chemo)
- Bevacizumab use with caution due to MOA
Initial Therapy options: Initial adjuvant/primary chemotherapy
- Stage 1A and 1B (grade 1): surgery then observation
- Stage 1A and 1B (grade 2): observation vs platinum-based chemo
- Stage 1A and 1B (grade 3) or stage 1C: platinum-based chemo
- Stages II-IV: platinum-based chemo
NOTE:
- Available regimens vary based on staging
- A taxane + platinum are the standard of care
Initial Therapy options
Stage 1: Chemotherapy… preferred options? other options?
Preferred:
- Paclitaxel/carboplatin q3weeks x 3 cycles
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Other options:
- Carboplatin/liposomal doxorubicin
- Docetaxel/carboplatin
Initial Therapy options
Stage II-IV: Chemotherapy… preferred options? other options?
Initial Therapy options
Intraperitoneal (IP) chemotherapy
Initial Therapy options
Frontline maintenance therapy
- Following adjuvant/primary therapy
- Patient must have complete (CR) or partial response (PR) from primary therapy
- Duration: depends on the regimen some are up to 24-36 months, others are until disease progression
Initial Therapy options
PARP inhibitors in ovarian cancer…what are the 3? and what is the one you should know info about?
Olaparib (Lynparza)
Niraparib (Zejula)
Rucaparib (Rubraca)
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Niraparib dosing
- Initial dosing studied: 300 mg PO once daily (~70% of patient required a dose reduction)
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- Initial dose adjustment for certain higher risk patients: < 77 kg or with a plt count <150,000/mm3
——- Start at 200 mg PO daily
——– After 2-3 months without hematologic toxicity can consider dose increase to 300 mg PO daily
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- If both patient’s weight ≥ 77 kg and plt ≥ 150,000/mm3
——- Start at 300 mg PO daily
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NOTE: Weekly labs require for monitoring all new starts
Initial Therapy options
Bevacizumab (Avastin) for ovarian cancer…MOA, side effects, dosing, etc
- MOA: Vascular Endothelial Growth Factor (VEGF) inhibitor
- Dosing: 15 mg/kg IV q3weeks (or 10 mg/kg IV q2weeks)
- Many biosimilars
- Common side effects: proteinuria, hypertension
- Hold for ≥6 weeks prior to surgery to reduce post-operative healing complications
Switching gears to Recurrence ovarian cancer (NOT initial anymore!)…goal? importance?
- Goal of therapy: No longer curable, new goal is to improving quality of life and reduce symptoms
. - Platinum free interval: time between completed chemotherapy to recurrence
1.) > 6 months (more than 6 months) = platinum sensitive disease
—- Recommendation to continue with platinum backbone (carboplatin or cisplatin)
—- Can consider secondary cytoreduction or maintenance therapies
2.) < 6 months (less than 6 months)= platinum resistant disease - No standard of care for regimen selection outside of determining platinum sensitivity
Platinum-sensitive: maintenance following
recurrence treatment
- Bevacizumab monotherapy (if previously treated with chemo + bevacizumab)
. - PARPi: Olaparib, Rucaparib, Niraparib
Summary of PARPi in ovarian cancer
