Ovarian Cancer...Ovarian Cancer Incidence/Mortality 5 year overall survival \ 伀匀尩 rate of pts...
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Transcript of Ovarian Cancer...Ovarian Cancer Incidence/Mortality 5 year overall survival \ 伀匀尩 rate of pts...
Ovarian Cancer Incidence/Mortality
Presenter
Presentation Notes
5 year overall survival (OS) rate of pts across ALL stages of ovarian cancer: 48% But if diagnosed with advanced disease, only 28% 5-year survival rate Before we high five ourselves there are disparities and not all groups are headed in the right direction 1975/1989/2014 all/white/black Ovary 36 38 48/ 35 38 47 /42 34 39
Improvement in 5 Year Survival:
Race 1975 1989 2014
All 36% 38% 47%
White 35% 38% 48%
African American 42% 34% 39%
Noone AM, Howlader N, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975-2015, National Cancer Institute, Bethesda, MD, www.seer.cancer.gov/csr/1975_2015/, based on November 2017 SEER data submission, posted to the SEER website April 2018.
Presenter
Presentation Notes
Just a reminder of the stats as they are….. Most likely due to more lines of therapy rather than better 1L therapy Still a 11% improvement in 40 years? We have a lot of room for improvement but as we all know,
Ovarian Cancer Facts and Figures
-5 year overall survival (OS) rate across ALL stages of ovarian cancer: 47%
-If diagnosed with advanced disease: 28%
Presenter
Presentation Notes
5 year overall survival (OS) rate of pts across ALL stages of ovarian cancer: 48% But if diagnosed with advanced disease, only 28% 5-year survival rate Before we high five ourselves there are disparities and not all groups are headed in the right direction 1975/1989/2014 all/white/black Ovary 36 38 48/ 35 38 47 /42 34 39
Ovarian Cancer Risk
Factors
Not a comprehensive list of risk factors for ovarian cancer; BRCA = breast cancer susceptibility gene; BMI = body mass index; HRT = hormone replacement therapy.
1. What are the risk factors for ovarian cancer?. Atlanta, GA: American Cancer Society. Last revised February 4, 2016. http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-risk-factors. Accessed July 24, 2017. 2. Wei JJ, et al. Int J Gynecol Pathol. 2011;30:553-568.
• Age• Obesity• Genetics
• Family history (1st degree relatives)• BRCA• Lynch syndrome• Peutz-Jeghers syndrome• Cowden syndrome
• Endometriosis• Medications
• Hormone replacement therapy
• Protective factors:• Birth control pills, childbirth before age 26,
tubal ligation
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Presentation Notes
Positive Risk Factors Largely a disease of menopausal women Those with BRCA tend to develop younger Lynch syndrome – hereditary nonpolyposis colorectal cancer increases OC risk by 12% (40-60% for uterine cancer) Peutz-Jeghers syndrome – rare genetic disorder that develops polyps in the stomach and intestine Cowden disease – mutation in PTEN gene; increases risk of thyroid cancer, breast cancer but also OC Talcum powder – applied to genital area or on sanitary napkin can be carcinogenic Negative RF Reproductive history: women who give birth < 26yo lower risk of OC Birth control use – risk is lower the longer the pills are used
~20%–22% of patients with ovarian cancer 14%–15% are associated with hereditary germline BRCA1 or BRCA2
mutations (gBRCAmut)1
~6%–7% are associated with somatic BRCA mutations (sBRCAmut)1
Risk of Ovarian Cancer among BRCA carriers:
39% of BRCA1 develop ovarian cancer by age 703,4
11%–17% of BRCA2 develop ovarian cancer by age 703,4
1% lifetime risk for the general female population1
BRCA Mutations
Konstantinopoulos PA et al. Cancer Discov. 2015;5:1137-54; Liu JF et al. Gynecol Oncol. 2014;133:362-369; Antoniou A et al. Am J Hum Genet. 2003;72:1117-1130; Chen S, Parmigiani G. J Clin Oncol. 2007;25:1329-1333.
CA125
Best known marker in ovarian cancer Present in 79%
90% of advanced cases
50% of early cases
Also elevated in benign conditions Endometriosis, benign breast changes,
inflammatory conditions Can be elevated in other cancers
Presenter
Presentation Notes
CA-125 has limited specificity for ovarian cancer because elevated CA-125 levels can be found in individuals without ovarian cancer. For example, while CA-125 is best known as a marker for ovarian cancer,[24] it may also be elevated in other cancers, including endometrial cancer, fallopian tube cancer, lung cancer, breast cancer and gastrointestinal cancer.[4] CA-125 may also be elevated in a number of relatively benign conditions, such as endometriosis,[25] several diseases of the ovary, menstruation[22] and pregnancy.[26] It also tends to be elevated in the presence of any inflammatory condition in the abdominal area, both cancerous and benign.[27] Thus, CA-125 testing is not perfectly specific for ovarian cancer and often results in false positives.[22] The specificity of CA-125 is particularly low in premenopausal women because many benign conditions that cause fluctuations in CA-125 levels, such as menstruation, pregnancy, and pelvic inflammatory disease, are seen in this population.[21] CA-125 testing is also not perfectly sensitive for detecting ovarian cancer because not every patient with cancer will have elevated levels of CA-125 in their blood.[28] For example, 79% of all ovarian cancers are positive for CA-125, whereas the remainder do not express this antigen at all.[29] Also, only about 50% of patients with early stage ovarian cancer have elevated CA-125 levels.[30] Since many patients with early stage ovarian cancer do not have elevated levels of CA-125, this biomarker has poor sensitivity for ovarian cancer, especially before the onset of symptoms.[22] Soooooo… does this marker have much to offer?
Screening?
Screening?
NCCN=National Comprehensive Cancer NetworkAmerican Congress of Obstetricians and Gynecologists (ACOG) Committee Opinion. http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Gynecologic-Practice/The-Role-of-the-Obstetrician-Gynecologist-in-the-Early-Detection-of-Epithelial-Ovarian-Cancer. Accessed March 24, 2015.
The FDA, US Preventative Services Task Force, American Collegeof Obstetrics and Gynecologists, Society of Gynecologic Oncology,
and NCCN recommend AGAINST ovarian cancer screening
Presenter
Presentation Notes
No test is sensitive enough to use in screening So, the earliest detection is from symptoms
Signs and Symptoms:
American Society of Clinical Oncology. https://www.cancer.net/cancer-types/ovarian-fallopian-tube-and-peritoneal-cancer/symptoms-and-signs
Most Common Symptoms• Bloating • Pelvic or abdominal pain
or pressure • Trouble eating or feeling full
quickly • Urinary symptoms
(urgency or frequency)
Other Nonspecific Symptoms• Fatigue • Upset stomach • Back pain • Constipation • Pain with intercourse • Menstrual changes • Abdominal swelling • Weight loss
Presenter
Presentation Notes
As we all know: S/S of ovarian cancer are often difficult to link to the diagnosis Vague Often attributed to other causes
Diagnostic Work-up
CA-125 = cancer antigen 125; CT = computed tomography; MRI = magnetic resonance imaging; PET = positron emission tomography. 1. American Society of Clinical Oncology. https://www.cancer.net/cancer-types/ovarian-fallopian-tube-and-peritoneal-cancer/symptoms-and-signs. Accessed Oct 21,2019;
Imaging1
• Transvaginal ultrasound• CT or MRI scan• PET-CT scan • Chest imaging• Pelvic or abdominal
ultrasonography
CA-1251
• Serum tumor marker• Low predictive value for
detecting ovarian cancer in women without special risk factors2
• Nonspecific for ovarian cancer3
• Along with other tumor markers (e.g. CA 19-9) can be used to aid diagnosis
Summary1
• Ovarian cancer has largely nonspecific symptoms3
• Initial diagnosis is made by: 1. Physical exam 2. Tumor markers3. Laboratory tests 4. Radiology imaging
• Biopsy usually done at time of first surgery
• Staging is done at the time of surgery
Physical Exam• Abdominal / pelvic exam
• Mass• Ascites• Distension
Presenter
Presentation Notes
Interesting: Biopsy most commonly not done until first surgery Perform staging at time of surgery!!
WHO = World Health Organization.1. Ehdaivand S. WHO classification of ovarian neoplasms. Pathology Outlines. Revised May 19, 2016. http://www.pathologyoutlines.com/topic/ovarytumorwhoclassif.html. Accessed August 17, 2017. 2. Bodurka DC, et al. Cancer. 2012;118(12):3087-3094. 3. Prat J. Ann Oncol. 2012;23(Suppl 10):x111-117.
Histological Subtypes
Germ cells
Epithelium
Stroma
• WHO histological typing of ovarian cancer is based on cell lineage1
– Epithelial cells– Germ cells – Sex chord and stromal cells
Endometrioid 10%
Clear-Cell 10%
Epithelial Ovarian Carcinoma Subtypes
High-grade Serous 70%
Mucinous 3%Low-grade Serous <5%
Other 2%
Ovarian tumor cell lineage
Serous ovarian tumors are typically graded using a 2-tier system2
FIGO Staging
FIGO=International Federation of Gynecology and Obstetrics.1. Society of Gynecologic Cancer. https://www.sgo.org/wp-content/uploads/2012/09/FIGO-Ovarian-Cancer-Staging_1.10.14.pdf. Accessed July 12, 2016; 2. College of American Pathologists. http://www.cap.org/ShowProperty?nodePath=/UCMCon/Contribution%20Folders/WebContent/pdf/cp-ovary-fallopian-16protocol-1000.pdf. Accessed July 12, 2016.
Histologic grade is included as criteria for staging of all subtypes except clear cell and serous ovarian cancer2
FIGO Stage1 Description
I The cancer is confined to the ovaries or fallopian tube(s)
II The cancer is in one or both of the ovaries and has spread below the pelvis
IIIThe cancer is in one or both of the ovaries and has spread in the peritoneal area outside of the pelvis and surrounding nodes
IV The cancer has spread to organs beyond the ovaries and the peritoneal area
Presenter
Presentation Notes
Staging of Ovarian Cancer Is Done at the Time of Surgery or by Sampling Tumor Tissue or Ascitic Fluid Key points: Stage I ovarian or fallopian tube cancer is confined to the ovaries or the fallopian tubes and peritoneal fluid/washings. Key points: Stage II is defined as extension or metastasis to extraovarian/extratubal pelvic organs and may include curable tumors that have directly extended to adjacent organs but have not yet metastasized, as well as tumors that have seeded the pelvic peritoneum by metastasis. Key points: Most ovarian cancers are high-grade serous carcinomas that usually present in stage III, with the vast majority stage IIIC. Key points: Stage IV is defined as distant metastasis and includes patients with parenchymal liver/splenic metastases and extra-abdominal metastases. Distant metastasis beyond peritoneal metastases Pleural effusion with positive cytology Parenchymal metastases and metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside of the abdominal cavity)
5 Year Survival by Stage
Surveillance, Epidemiology, and End Results (SEER) Program Cancer Statistics Factsheets: Ovary Cancer. Bethesda, MA: National Cancer Institute, 2017. http://seer.cancer.gov/statfacts/html/ovary.html. Accessed August 18, 2017.
Majority of ovarian cancer cases are diagnosed at an advanced stage*
Stage at Diagnosis 5-Year Survival by Stage
0
10
20
30
40
50
60
70
Perc
ent o
f Ova
rian
Ca
ncer
Ca
ses b
y St
age
(%)
15 19
6
60
0
10
20
30
40
50
60
70
80
90
100
Stage I Stage II StageIII/IV
Unstaged
Perc
enta
ge o
fPa
tient
s Sur
vive
d
Stage
Survival rate declines as stage at diagnosis increases
92.5
73.0
28.9 25.1
Despite advances in treatment 85% of those diagnosed with
advanced stage Ovarian Cancer will recur.
Presenter
Presentation Notes
Typically diagnosed with advanced dz Despite surgical advances and good treatment 85% will have recurrence With each recurrence the PFS or CTFI becomes shorter and shorter We have a real need in this disease to improve outcomes or, at very least move the chains on that interval
Adapted from Ovarian Cancer National Alliance. http://www.ovariancancer.org/about/treatment/. Accessed July 13, 2016.Ushijima K. J Oncol. 2010;2010:497429.
0
10
20
30
40
50
60
70
80
90
100
I II III IV
Perc
ent (
%)
Stage
10
30
70-9090-95
Recurrence Rates by Stage of Diagnosis
• ~70% of all patients diagnosed with ovarian cancer (all stages) will have a recurrence1
• Recurrent ovarian cancer is treatable but not curable
After Each Subsequent Treatment, Median Progression-Free Survival (PFS) Shortens During Watchful Waiting
*PFS was calculated from the day of randomization (day of first cycle of chemotherapy) to the first disease progression.PFS = progression-free survival; L = line. Hanker LC, et al. Ann Onc. 2012;23:2605-2612. Lorusso D, et al. Int J Surg Oncol. 2012;2012:613980.
1L
RECURRENCE
Diagnosed with ovarian cancer
2L
6L
3L4L
5L
RECURRENCE RECURRENCE RECURRENCE RECURRENCE
Median PFS~18 mo
Median PFS*10.2 mo (9.6–
10.7) Median PFS*6.4 mo(5.6–7.0) Median PFS*
5.6 mo(4.8–6.2) Median
PFS*4.4 mo (3.7–4.9)
Median PFS*
4.1 mo (3.0–5.1)
Ovarian cancer recurs, receives active line of treatment
Presenter
Presentation Notes
Data from meta-analysis of multiple phase 3 trials: see references for more information 90% of women will have recurrence within 2 years
Overview of Ovarian Cancer Treatment
Systemic Treatment -before surgery (neoadjuvant)
GoalReduce tumor burden
prior to surgery
Surgery-Staging-Primary debulking surgery (PDS)-Interval debulking surgery (pre and post chemo)
Goal-Curative intent-Reduce tumor burden
Systemic Treatment-First-line/adjuvant therapy -Recurrence therapy-Maintenance therapy-Clinical trials
Goal-Curative intent-Control symptoms-improve QOL
Supplemental Therapy -Observation – “watch and wait” -Maintenance therapy
GoalExtend platinum –sensitivityExtend chemotherapy-free interval-Extend disease-free int.
National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer (Version 2.2019). Accessed Oct. 2019.
Presenter
Presentation Notes
The type of surgical procedure is based on the extent of the disease Residual disease <1 cm defines optimal cytoreduction Complete cytoreduction is defined as no visible residual disease Interval cytoreduction can be performed after ≤4 cycles of neoadjuvant chemotherapy; consultation with a gynecologic oncologist is recommended Fertility-sparing surgery: USO can be considered for�early-stage disease; refer to reproductive endocrinologist for evaluation and consultation, as clinically needed Secondary cytoreduction: can be considered in patients with recurrent disease ≥6–12 months after initial surgery if isolated or limited foci without ascites
NCCN Guidelines: First-line Treatment
*Stage IA or IB, Grade 1; †Stage IA or IB, Grade 3 or Stage IC, any grade. Stage IA or IB, Grade 2 has choice of either no treatment (observation) or adjuvant chemotherapy.Chemo=chemotherapy; CR=complete response; NCCN=National Comprehensive Cancer Network; PD=progressive disease; PR=partial response; SD=stable disease; SOC=standard of care.National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer (Version 2.2018)
Ovarian cancer classificationCurrent SOCLess commonly used
Clinical trial
Observation
OR
Achieved CR
OR
Persistent or Recurrent Disease
PR, SD or PD
Clinical relapse
SurgeryNeoadjuvant therapy
Locally Advanced
Stages II & III
MetastaticStage IV
Primary (adjuvant)
chemo
“Interval debulking”
Surgery
Adjuvant chemo
No treatment (observation)Low
grade*
High grade†
LocalizedStage I
Monitoring & follow-up
Maintenancetherapy
Surgery
Should be considered
for all stages
By a Gyn oncologist
Type of procedure is based on
extent of disease
Goal: no visible
residual disease
Presenter
Presentation Notes
The type of surgical procedure is based on the extent of the disease Residual disease <1 cm defines optimal cytoreduction Complete cytoreduction is defined as no visible residual disease Interval cytoreduction can be performed after ≤4 cycles of neoadjuvant chemotherapy; consultation with a gynecologic oncologist is recommended Fertility-sparing surgery: USO can be considered for�early-stage disease; refer to reproductive endocrinologist for evaluation and consultation, as clinically needed Secondary cytoreduction: can be considered in patients with recurrent disease ≥6–12 months after initial surgery if isolated or limited foci without ascites
Chemotherapy
NeoadjuvantAdjuvantMetastaticIntraperitoneal
First-line Treatment: Stage I
Intraperitoneal/Intravenous Regimen
Level of Evidence/Recommendation
Intravenous regimens
Paclitaxel + Carboplatin day 1. Repeat q3wk × 3-6 cycles (preferred) Category 2A
Carboplatin + pegylated liposomal doxorubicin every 4 weeks for 3-6 cycles Category 2A
Docetaxel + Carboplatin day 1. Repeat q3wk × 6 cycles Category 2A
NCCN=National Comprehensive Cancer Network; IV=intravenous; IP=intraperitoneal; q3wk=every 3 weeks. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer (Version 2.2018)
First-line Treatment: Stage II-IVIntraperitoneal/Intravenous Regimen
Level of Evidence/Recommendation
Intraperitoneal/Intravenous regimensPaclitaxel IV day 1; Cisplatin IP day 2 after IV Paclitaxel; Paclitaxel IP day 8. Repeat q3wk × 6 cycles
Category 2A
Intravenous regimensPaclitaxel + Carboplatin day 1. Repeat q3wk × 6 cycles Category 2A
Dose-dense Paclitaxel days 1, 8, and 15, followed by Carboplatin day 1.Repeat q3wk × 6 cycles
Category 2A
Paclitaxel + Carboplatin day 1. Weekly for 18 weeks Category 2A
Docetaxel + Carboplatin day 1. Repeat q3wk × 6 cycles Category 2A
Carboplatin + pegylated liposomal doxorubicin every 4 weeks for 6 cycles Category 2A
Bevacizumab-containing regimens per ICON-7 and GOG-218Paclitaxel IV + Carboplatin IV + bevacizumab IV day 1. Repeat q3wk × 5–6 cycles. Continue bevacizumab up to 12 additional cycles for maintenance
Category 2A
Paclitaxel IV + Carboplatin IV day 1. Repeat q3wk × 6 cycles Starting day 1 of cycle 2, give bevacizumab IV q3wk up to 22 cycles
Category 2A
NCCN=National Comprehensive Cancer Network; IV=intravenous; IP=intraperitoneal; q3wk=every 3 weeks. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer (Version 2.2018)
Intraperitoneal chemotherapy HIPEC - Hyperthermic
Most of OC have spread to peritoneum by the time of diagnosis Intraperitoneal (IP) chemotherapy prolonged survival time and
reduced the risk of death. Higher rate of adverse events and the frequency of
discontinuation hampered adoption Abdominal pain, Nausea, Vomiting, Fatigue, Infection, Ileus
Hyperthermia enhanced cancer cell destruction HIPEC-based regimens might PFS and OS for patients with
advanced primary ovarian cancer. Benefit still under debate
Zhang, G., Zhu, Y., Liu, C. et al. The prognosis impact of hyperthermic intraperitoneal chemotherapy (HIPEC) plus cytoreductive surgery (CRS) in advanced ovarian cancer: the meta-analysis. J Ovarian Res 12, 33 (2019) doi:10.1186/s13048-019-0509-1
Presenter
Presentation Notes
Meta analysis of 13 studies After every cycle of IP chemotherapy finished, the risk of death decreased by 12% [3] Hyperthermia produced an increased lysosomal enzyme activity; enhanced cancer cell destruction
Definition of Response to First-Line Chemotherapy: NCCN Guidelines
CT=computed tomography; ULN=upper limit of normal.National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer (Version 2.2018); Nishino M et al. AJR Am J Roentgenol. 2010;195:281-289.
Complete response (CR): Negative physical
exam
Negative CA-125
Negative CT with <1cm lymph nodes
Partial response (PR): ≥ 30% reduction in
the sum of diameters compared to baseline
Persistence of 1 or more non-target lesions
AND/OR CA-125 above ULN
Progressive disease (PD): ≥ 20% increase in the
sum of diameters of target lesions
The sum must demonstrate an absolute increase of ≥ 5mm
OR Appearance of one
or more new lesions
Presenter
Presentation Notes
nl CA125 = 0-35
Then what???
BRCA mutation in Ovarian Cancer
BRCA is tumor suppressor gene involved in repair of DNA double strand breaks
When mutated that mechanism is damaged Germ-line BRCA (gBRCAmut) improved PFS and OS In relapse setting: improved response to 2nd line therapy even if early
relapse Platinum and non platinum
Non gBRCAmut who respond to multiple lines likely to have somatic BRCA mutation (sBRCAmut) or other mutations
Presenter
Presentation Notes
Germline BRCA good or bad? Patients carrying germ-line mutations had improved rates of progression-free and overall survival. In the relapse setting, patients carrying mutations more frequently responded to both platin- and nonplatin-based regimens than mutation-negative patients, even in patients with early relapse after primary treatment. Mutation-negative patients who responded to multiple cycles of platin-based treatment were more likely to carry somatic BRCA1/2 mutations. J Clin Oncol. 2012 Jul 20; 30(21): 2654–2663. Published online 2012 Jun 18. doi: 10.1200/JCO.2011.39.8545 PMCID: PMC3413277 PMID: 22711857 BRCA Mutation Frequency and Patterns of Treatment Response in BRCA Mutation–Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group Kathryn Alsop, Sian Fereday, Cliff Meldrum, Anna deFazio, Catherine Emmanuel, Joshy George, Alexander Dobrovic, Michael J. Birrer, Penelope M. Webb, Colin Stewart, Michael Friedlander, Stephen Fox, David Bowtell, and Gillian Mitchell
Genetic Mutations Beyond BRCA Mutations May Lead to Homologous Recombination Deficiency (HRd)
OTHER (may be HR deficient via upregulation of miRNAs or other mechanisms)
HR DEFICIENT
HR PROFICIENT
POSSIBLY HR DEFICIENT
HR=homologous recombination; NER=nucleotide excision repair; MMR=mismatch repair; PTEN=phosphatase and tensin homolog.Konstantinopoulos PA et al. Cancer Discov. 2015;5:1137-54; Liu JF et al. Gynecol Oncol. 2014;133:362-369; Antoniou A et al. Am J Hum Genet. 2003;72:1117-1130; Chen S, Parmigiani G. J Clin Oncol. 2007;25:1329-1333.
Presenter
Presentation Notes
HRD can result from BRCA1/2 mutations There are also many other HRD types of mutations
Homologous Recombination (HRd)DNA errors in replication commonDNA damage repair through the highest
fidelity mechanism = homologous recombination
HRd or HRp In BRCAmut: part of the mechanism is
absent = HRdPARPs required
Presenter
Presentation Notes
Replicate millions of cells, errors inevitably happen, i.e. manually transcribing a million numbers When errors occur a couple of ways that DNA gets repaired. Most accurate is HR. Spots the errors Recruits PARP enzymes and others to assist in repair Remember BRCA is a tumor repair gene, “anti- oncogene”, helps in DNA repair. If BRCA mut that helper is already missing
PARP inhibitors
Poly ADP ribose polymerase - enzymes involved in DNA repair through HR
Single strand DNA breaksPARP inhibitors block the ability of PARPs to
participate in DNA damage repairMost effective in BRCAmut and HRdOral agents: dosed qd or bid
PARP inhibitors
QOL similar between PARP and placeboSide effects depend on which PARP
Nausea / vomitingFatigueThrombocytopenia, neutropenia, anemia
HRd
HRp HRd HRd + PARP
Maintenance Avastin in maintenance if used with 1L PARPs Previously indicated after recurrence and subsequent
chemotherapy Stretched the PFS after 2L in special populations
Some for gBRCA
Some for gBRCA or tBRCA (same as sBRCA)
Some for HRd
Some showed activity in HRp
Newest data shows advantage in 1L maintenance Goal: to maintain platinum sensitivity, increase PFS
Presenter
Presentation Notes
Lots of Buzz this year at SGO, ASCO, most recently ESMO 1L New enough not to be in NCCN guidelines yet. SOLO 1 trial early this year maintenance in gBRCA pts after a response to plat signif increased PFS
Goal: Increase PFS with each subsequent line
*PFS was calculated from the day of randomization (day of first cycle of chemotherapy) to the first disease progression.PFS = progression-free survival; L = line. Hanker LC, et al. Ann Onc. 2012;23:2605-2612. Lorusso D, et al. Int J Surg Oncol. 2012;2012:613980.
1L
Diagnosed with ovarian cancer
2L
3L
RECURRENCE RECURRENCE
Median PFS
Median PFS*
Ovarian cancer recurs, receives active line of treatment
Presenter
Presentation Notes
Increase PFS after 1L, 2L, even 4L
NCCN Guidelines: Maintenance Therapy
†Pazopanib is recommended as single-agent maintenance therapy if complete clinical remission following primary therapy for stage II-IV disease, if no prior bevacizumab (category 3).*Rucaparib, Olaparib, Niraparib are approved in the US for a non-maintenance indication.
Ledermann JA, Raja FA, Fotopoulou C, et al. Annals of Oncology. 2013;24(Supp 6):vi24-vi32; Ledermann JA, Sessa C, Colombo N. eUpdate-Ovarian Cancer Treatment Recommendations. Updated on: Sep. 21, 2016; http://www.esmo.org/Guidelines/Gynaecological-Cancers/Non-Epithelial-Ovarian-Cancer/eUpdate-Treatment-Recommendations; National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer (Version 2.2018).
For those with platinum-sensitive disease who have completed two or more lines of platinum-based therapy, consider niraparib maintenance therapy if partial or complete response
For those with BRCA1/2 mutations who have completed one or more lines of platinum-based therapy, consider olaparib maintenance therapy if partial or complete response
For platinum-sensitive recurrent disease, if response after chemotherapy, bevacizumab can be continued as maintenance therapy until disease progression or unacceptable toxicity
Niraparib Olaparib Bevacizumab
For those with platinum-sensitive disease who have completed two or more lines of platinum-based therapy, consider rucaparib maintenance therapy if partial or complete response
Rucaparib*
Presenter
Presentation Notes
These are not all maintenance: please modify the slide
Clinicaltrials.gov
2,498 Ovarian Cancer Trials764 Phase I1,011 Phase II233 Phase III
Presenter
Presentation Notes
This is the only way we make any strides in this disease
What about check point inhibitors?
Ovarian Cancer Clinical Trials
Ovarian cancer thought to be “cold” tumor Can it be “warmed up”? Combination trials with PARPi + immunotherapy agents Combination trials of avastin + PARPi Trials on rechallenging with a PARP +
Presenter
Presentation Notes
2,498 ovarian trials
Paradigm Shift
2011: 2 trials showed benefit of bevacizumab with first line therapy 2018: SOLO1 trial showed benefit of PARPi in gBRCAmut in 1L
maintenance Only 44% adopted
2019: ESMO – 3 trials showing benefit of PARPi in 1L maintenance in various populations (high risk, HRd, HRp, adding to chemo upfront and then following with maintenance, adding to bev) “PARPs Made the biggest splash”
“Game changer”
PARPs in 1L treatment, 1L maintenance, 2L maintenance, 3+L treatment.
Thank You!
