Management of recurrent EOC Flashcards
There are three biologies for HGS recurrent ovarian cancer. What are they?
What are treatment options for platinum sensitive recurrence?
-Also give the treatment options
Platinum + Paclitaxel
- ICON4: PFS 12 months vs 9 months (platinum only); survival advantage (OS 29 vs 24 months)
Carboplatin + gemcitabine
- AGO: PFS 8.6 months vs 5.8 months (carbo only)
PLD + Trabectedin
- OVA-301: PFS 9.2 vs 7.5 months (PLD only)
Carboplatin + PLD
- CALYPSO: PFS 11.3 vs 9.4 months (Carbo+taxol)
Carbo/Gem/Bev
- OCEANS: PFS: 12.4 vs 8.4 months (Carbo/Gem)
Carbo/Taxol/Bev
- GOG 213: PFS 13.8 vs 10.4 months (carbo/taxol); survival advantage (OS 42.2 vs 37.3 months)
Platinum/Paclitxel/Cediranib (concurrent +/- maintenance)
- ICON6: PFS 11.1 (chemo + cediranib + maintenance cediranib) vs 10.1 (chemo + cediranib) vs 8.7 months (platinum/taxol); survival advantage between maintenance vs chemo (OS 26.3 vs 20.3 months)
Discuss AURELIA and the results
Methods
Eligibility
- Platinum-resistant ovarian cancer
- <3 prior lines
- No refractory disease, hx bowel obstruction
Investigator selected chemotherapy
- pegylated liposomal doxorubicin
- weekly taxol
- topotecan
Randomized +/- bev until progression, unacceptable toxicity, or consent withdrawal.
Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone.
The primary end point was PFS.
Secondary end points included ORR, OS, safety, and PROs.
Results
ORR:11.8% vs 27.3% (P = .001).
OS
- HR: 0.85 (95% CI, 0.66 to 1.08; P < .174)
- mOS: 13.3 vs 16.6 months, respectively
Safety
- Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab.
- GI perforation occurred in 2.2% of bevacizumab-treated patients.
Summary slide of treatment options for platinum-resistant recurrence
What was AGO Desktop III?
what were the results?
- RCT
- Eligibility: 1st relapse, Plat-sensitive OVCA, AGO score +ve
- 2ndary cyto + platinum-based chemo vs platinum-based chemo only
- Results
- Survival advantage with surgery (see figure)
What are considerations for treatment planning for patients who recur?
- Treatment free interval
- Residual toxicity from prior therapy
- Volume of disease at the time of relapse
- Serologic relapse (CA-125)
What was SOC-1 and the design?
Was there any difference in the primary outcomes?
Prelim results show no difference in OS:
- surgery (58 mo) vs no surgery (54 mo)
- HR 0.82 (0.57 - 1.19)
PFS was added as a primary outcome:
- mPFS 17.4 (surgery) vs 11.9 (no surgery) months
- HR: 0.58 (95% CI 0.45 - 0.74; p <0.0001)
imodel score was based on 6 variables:
- FIGO stage
- residual disease after PCS
- PFS
- ECOG
- CA-125 at recurrence
- Presence of ascites at recurrence
Source: Tian WJ, Ann Surg Oncol 2012,19(2):597-604
What’s the role of bevacizumab in platinum-sensitive recurrence for maintenance therapy?
Therapies when platinum is not an option?
- Weekly paclitaxel (+/- bevacizumab)
- Pegylated liposomal doxorubicin (PLD) (+/- bevacizumab)
- Cisplatin and gemcitabine, gemcitabine alone
- Topotecan (+/- bevacizumab)
- Pemetrexed
- Metronomic cyclophosphamide
- PARP inhibition (HR Deficient)
What is the definition of platinum-sensitivity?
- The 6-months timeframe as a definition for platinum-sensitive vs platinum-resistant ovarian cancer patients is primarily for clinical trial purposes.
- Sensitivity and resistance to platinum is better viewed as a continuum.
- The definitions shown here for sensitivity were developed based on measurable ovarian cancer at first relapse and did not take into account CA-125 levels.
What are the endpoints and goals for treatment of platinum-recurrent OVCA?
- Treatment to progression
- Unacceptable toxicity
- Complete clinical remission
- Goal of palliation
How does platinum-free interval (PFI) correlate with second-line therapy efficacy?
Longer the PFI –> Better Response, better OS/PFS
Summary Slide trial designs of GOG-213 vs Desktop III vs SOC-1
What are treatment options for ovarian cancer patients with relapse after 6 months following frontline therapy?
- Depends on radiographic/and or clinical relapse vs biochemical relapse (CA-125 elevated with no radiologic evidence of disease)
- Treatment options
- Consider secondary cytoreduction
- Combination-platinum based chemo
- Clinical trial
- Consider delay treatment until clinical relapse if only biochemical relapse
- Best supportive care (unlikely)
- Combination of methods
What is the AGO-score?
AGO-score +ve if contains all 3:
- PS ECOG 0
- ascites ≤500 ml
- complete resection at initial surgery
What are the takeaways from GOG-213 vs Desktop III vs SOC-1?
What’s the bottom line about secondary cytoreduction?
- Takeaways
- Criteria for patient selection was reasnable across studies (>=66 CGR) but better with validated tools
- Impact of surgery of PFS and OS remarkably consistent across all 3 trials
- Desktop III and SOC-1 have similarly performing control arms
- Desktop III prognostically more favorable
- Outlier is GOG-213’s control arm
- Much higher use of bevacizumab (demonstrated in several trials to be superior to chemotherapy alone)
- Bottom line
- Secondary cytoreduction
- clear selection criteria are necessary
- Goal should always be R0
- Bevacizumab is the great equalizer
- Secondary cytoreduction
When do patients with advanced EOC recur?
Most patients recur between 18 - 24 months
Summary of survival outcomes of GOG-213 vs Desktop III vs SOC-1
For the current FDA-approved treatment options for platinum-sensitive recurrence:
- median PFS range?
- CR rate and duration?
- Platinum-based doublets and treatments to consider the most?
- 8.4 - 12 months
- 20% with >50% more than 6 months DOR
- Platinum-based doubles with PLD, Gemcitabine, and Paclitaxel; bevacizumab for most
What was GOG 213?
what were the results?
GOG 213 (n = 485)
- RCT to assess 2ndary cytoreduction in platinum-sensitive recurrent OVCA
- Investigator-determined resectable disease (to R0)
- adjuvant chemo carbo/taxol +/- bev (investigator-discretion)
- 2ndary cytoreduction + chemo vs chemo only
- Primary Endpoint = OS
- Results
- R0 in 67% of patients
- F/U 48.1 months
- Bev in 84% of patients overall
- No difference in OS/PFS
What are surgical trials for recurrent ovarian cancer?
What were their endpoints?
PFI is now replaced with what?
- Platinum-free interval is no longer the only factor to consider when selecting therapy
- The historical definition of using platinum-free interval (PFI) to categorize patients as having platinum-sensitive or resistant disease is now replaced by therapy-free interval (TFI)
- Patients for whom platinum is an option (formerly platinum-sensitive)
- Patients for whom platinum is not an option (formerly platinum-resistant)
1) What proportion of patients with advanced EOC will recur after initial therapy?
A) Overall?
B) they initially have large-volume advanced disease?
C) What about small-volume advanced disease?
2) What if they have limited disease?
A) high-risk limited disease?
B) low-risk limited?
1)
A) 60 - 80%
B) 80 - 95%
C) 60 - 70%
2)
A) 20%
B) 10%
What proportion of advanced EOC patients will have persistent disease or be refractory to frontline therapy?
20%
