Endometrial Cancer Flashcards
CONSORT Aim
To investigate whether the addition of systematic PLND to standard surgery improved OS and DFS in pts with peri-operative stage I EC
CONSORT results
5yr DFS 81% (LND) vs 81.7% (no LND)
OS 85.9% (LND) vs 90% (no LND)
CONSORT conclusion
The addition of systematic pelvic LND to hyst/BSO did not improve DFS or OS compared to no LND (aka no therapeutic benefit of LND)
ASTEC aim
To assess therapeutic benefit of pelvic LND in EC confined to the corpus
ASTEC inclusion
LR= IA, IB, and G1, G2
Intermediate/HR=IA or IB w/ high grade (G3, serous, CC)
Advanced=spread beyond the corpus
ASTEC results
Sx only= 802, Sx+LND=701
5yr OS 81% (sx) vs 80% (sx+LND)
5yr RFS 79% vs 73%
ASTEC conclusion
There is no evidence of a benefit for systematic LND for EC in terms of OS, RFS, and cannot be recommended for therapeutic purposes
LAP2 aim
To compare perioperative morbidity and mortality between laparoscopy and laparotomy for the stating of uterine cancer
LAP2 Inclusion
Stage I to IIA uterine cancer (1988 staging)
LAP2 results
TLH= 1630, TAH=886
-25.8% converstion to TAH
-op time longer in TLH
-no differences in complications, readmit, reoperation
-1.14% difference in recurrence at 3yrs
-0.24% trocar site recurrence (3 of 4 had advanced dz)
-5yr OS 89.8% in both
-5yr recurrence 11.61% (TAH) vs 13.68% (TLH)
LAP2 Results
Laparoscopic comprehensive surgical staging for uterine cancer is feasible and has an improved safety profile compared to laparotomy
SENTI-ENDO aim
To assess detection rate and diagnostic accuracy of SLN in predicting the pathological pelvic node status in patients with early stage EC (using tech-99)
SENTI-ENDO inclusion
Stages I and II EC
SENTI-ENDO results
at least one SLN in 111/125 (88.8%)
-B/l mapping in 62%
-for hemipelvis: NPV 100%, sensitivity 100%
-for patient: NPV 97%, sensitivity 84%
-FN rate 6%
-SLN upstaged 10% of LR and 15% of IR
SENTI-ENDO conclusion
SLN biopsy could be a trade off between systematic LND and no dissection in patients at low and IR and could provide important data to tailor adjuvant therapy
FIRES aim
To estimate the sensitivity and NPV of SLN mapping using RA-fluorescence imaging of the tracer indocyanine green in detecting lymphatic mets in pts with EC
FIRES inclusion
documented EC of ANY histology from endometrial sampling, clinical stage I
FIRES results
-86% successful mapping of at least 1SLN
-b/l mapping 52%
-sensitivity 97.2%, NPV 99.6%
-FN rate 2.8%
-1pt w/ FN had serous papillary
FIRES conclusion
SLN mapping with ICG can safely replace LND.
SLN mapping will not identify 3% of patients with nodal dz, but will expose fewer patients to the morbidity of complete LND
SENTOR aim
To evaluate the performance of SLN using ICG in patients with stage 1 dz, with IR and high grade subtypes
SENTOR inclusion
Clinical stage IG2 endometrioid
High grade (G3, serous, CC, carcinosarcoma, undiff/dediff)
SENTOR results
n=156
-all had PLND, 80% had PALND
-SLN detection rate: 97.4%/pt, 87.5%/hemipelvis, 77.6% b/l
-NPV 99.1%
-sensitivity 96%, FN 4%
-2/27 had single metastatic SLN identified outside of traditional PLN boundaries
PORTEC-1 Aim
To establish the role of post operative pelvic RT in Stage 1 EC
PORTEC-1 inclusion
All cell types
Stage IG1 w/ >50% MI
G2 w/ an MI
G3 w/ <50% MI
PORTEC-1 results
5yr OS 81% (RT) vs 85% NAT
Locoregional relapse 4% (RT) vs 14% (NAT)
PORTEC-1 conclusion
Postoperative RT improves locoregional control, but not OS
Whole pelvic RT should be reserved with HR patients
GOG 99 Aim
To establish whether RT improves RFI in patients with HIR EC
GOG 99 inclusion
HIR
-At least 70yo + 1RF
-at least 50yo + 2RF
-any age + 3 RF
RF= G2 or G3, outer 1/3 involvement, LVSI
GOG 99 results
-24mo recurrence: 3% RT vs 12% NAT
-HIR 6% vs 26%
-Local recurrence: 1.6% vs 8.9%
-distant recurrence: 5.3% vs 6.4%
-4yr OS: 92% (RT) vs 86% (NAT) p=0.557
GOG 99 conclusion
Whole pelvic RT reduces risk of recurrence by 58% but does not impact OS
Tx with RT should be limited to patients who fit HIR category
PORTEC-2 Aim
Whether VBT=EBRT in reduction of vaginal recurrence of EC
PORTEC-2 inclusion
HIR
PORTEC-2 Results
5yr OS 82.1% (EBRT) vs 86.2% (VBT)
5yr DFS 80.2% vs 84.5%
PORTEC-2 Conclusion
VBT is effective in ensuring local control and OS + DFS are similar to EBRT. Should be tx of choice for HIR EC
GOG 249 aim
Whether VBT/CT vs VBT alone has better RFS in women with HR, early stage EC
GOG 249 inclusion
GOG 99 HIR
Stage II (cvx) regardless of other RF
Serous or CC stage 1-2 w/ neg peritoneal cytology
GOG 249 results
5yr RFS 76% in both
5yr OS 87% (RT) vs 85% (VBT/CT)
no difference in rate of vaginal cuff recurrences
-PALN and pelvic recurrence: 4% vs 9%
-Distant recurrence: 2.5% vs 18%
RTOG 9708 Aim
Establish the safety and toxicity of RT and CT for endometrial cancer following surgery
RTOG 9708 inclusion
No metastatic dz outside the pelvis
-G2 or 3 w/ >50% MI
-stromal invasion of cervix
-extrauterine dz confined to pelvis and/or positive peritoneal cytology
RTOG 9708 arms
One arm observational
Pelvic RT 45Gy + Cis 50 day 1 and 28
VBT– LDR 20Gy or HDR 18Gy
After RT –> cis/taxol x4C
RTOG9708 Results
4yr pelvic recurrence 2%
4yr regional recurrence 19%
OS 85%, DFS 81%
Stage 3 pts: OS 77%, DFS 72%
No recurrences for stage IC, IIA, IIB
GOG 258 Aim
To evaluate the use of concurrent tumor volume directed EBRT and CT compared with CT alone
GOG 258 inclusion
Stage III or IVA EC of any type, surgical stage I or II CC, serous and positive washings
GOG 258 Arms
Arm 1: cis 50 w/ EBRT (45Gy, VBT PRN) followed by C/T x 4C
Arm 2: Carbo 6 AUC + taxol 175
GOG 258 results
n=370 (CT), n=366 (CRT)
5yr RFS 58% vs 59%
Vag recurrence: 7% vs 2%
Node recurrence: 20% vs 11%
Distant recurrence: 21% vs 27%
GOG 258 conclusion
The combined regimen of CRT is not superior to CT alone in prolonging RFS, but locoregional relapses were less frequent than with CT alone.
PORTEC 3 Aim
To evaluate the benefit of CRT vs RT alone on HR endometrial cancer
PORTEC 3 inclusion
Stage IAG3 w/ LVSI, IBG3, Stage II, Stage IIIA-C
Serous or CC stage IA w/ invasion, IB, II, or III
PORTEC 3 arms
CRT: Cis 50 x2 + 48Gy –> C/T x4C
RT: 4860 cGy (VBT 14Gy PRN)
PORTEC 3 results
5yr OS 81.8% (CRT) vs 76.7% (RT)
5yr FFS 75% vs 68.6%
PORTEC 3 Post hoc
Stage 3: 5yr OS 78.5% (CRT) vs 68.5% (RT)
Serous: OS 71.4% (CRT) vs 52.8% (RT)
PORTEC 3 conclusion
Combination of CT and RT does not significantly improve OS.
Should consider CRT for stage III and serous cancers, due to statistically significant increase in OS in post hoc analysis
GOG 107 Aim
To compare doxorubicin as a single agent against combo of doxorubicin + cisplatin
GOG 107 inclusion
Stage III, IV, or recurrent EC after surgery or RT
GOG 107 arms
Singlet: Doxorubicin 60mg/m2 q3wk
Doublet: Doxo 60 + cist 50 q3wk
GOG 107 results
PFS: 5.7mo (DC) vs 3.8 mo (D)
OS: 9mo vs 9.2mo
Overall response: 42% (DC) vs 25% (D)
GOG 107 conclusion
Response rate and PFS is significantly improved when cis is added to doxorubicin, but OS is not improved and there is more toxicity
GOG 163 aim
To determine whether 24hr paclitaxel plus doxorubicin is superior to cis/dox in patients with advanced EC
GOG 163 inclusion
Stage III or IV, or recurrent EC
GOG 163 arms
Standard: Doxo 60 + cis 50 x7C
Exp: Doxo 50 + taxol 150
GOG 163 results
OR: 40% (DC) vs 43% (DP)
PFS: 7.2mo vs 6mo
OS: 12.6mo vs 13.6mo
GOG 163 conclusion
Doxorubicin + taxol is not superior to doxorubicin + cis in advanced EC
GOG 177 aim
To compare TAP (taxol, doxorubicin, cis) to AP (doxorubicin, cis) in terms of RR, PFS, and OS
GOG 177 inclusion
Stage III, IV, or recurrent EC
GOG 177 arms
AP: Doxo 60 + cis 50
TAP: doxo 45 + cis 50 + taxol 160
7C, q 3 weeks
GOG 177 results
OR: 57% (TAP) vs 34% (AP)
PFS: 8.3mo vs 5.3mo (SS)
OS: 15.3mo vs 12.3mo (SS)
GOG 177 conclusion
TAP significantly improves RR, PFS, and OS compared with AP. There is an increased risk of peripheral neuropathy
GOG 122 aim
To compare WAI to doxo-cis in patients with advanced EC
GOG 122 inclusion
Stage III or IV of any histology
GOG 122 arms
RT: 30Gy WAI, 15Gy pelvis +/- PALN boost
CT: Doxorubicin 60 + Cis 50 q3wks x 8C
GOG 122 results
5yr PFS 42% (CT) vs 38% (RT)
5yr OS 53% vs 42%
Gross residual disease associated with significantly shorter PFS but not OS
GOG 209 aim
To determine if carboplatin and taxol could replace TAP as first line treatment in advanced or recurrent EC based on non-inferior efficacy
GOG 122 conclusion
In advanced EC, CT significantly improves PFS and OS compared to RT, but causes more frequent and severe acute toxicity
GOG 209 inclusion
Measurable and non measurable primary stage III, IV, or recurrent EC
GOG 209 arms
AP: Doxo 45 + cis 50 + taxol 160
TC: carbo AUC 6 + taxol 175
both q3 wks, up to 7C
GOG 209 results
TAP=656, CT+672
PFS 14mo (TAP) vs 13mo (TC)
OS 41mo vs 37mo
OR 52% for both
GOG 209 conclusion
Carbo/taxol is not inferior to TAP and should be considered first line therapy for advanced or recurrent EC
Fader et al Aim
To quantify the benefit conferred by adding trastuzumab to C/T in women with uterine serous whose tumors overexpress HER2/neu in primary and recurrent dz
Fader inclusion
primary advanced (III or IV) or recurrent (any stage) HER2+ serous, optimal or suboptimal debulk, no more than 3 prior chemos
Fader arms
Control: carbo 5AUC + taxol 175 q21d x 6C
Exp: C/T + trastuzumab 8mg/kg first dose, 6mg/kg subsequent, q21 days x 6 C w/ 6mg/kg maintenance until progression or unacceptable tox
Fader results
control=28, exp= 30
-71% with advanced dz, 29% w/ recurrent
-PFS 8mo (control) vs 12.6mo (exp)
-primary tx: 9.3mo vs 17.9mo
-recurrent: 6mo vs 9.2om
-2020 update: OS 24.4mo vs 29.6mo (exp)– most notable in primary tx of III-IV dz
Fader conclusion
The addition of C/T to HER2 positive uterine serous results in a 56% decrease in risk of progression relative to C/T alone
MITO END-2 aim
To compare C/T to combo C/T/Bev in patients with advanced or recurrent EC
MITO END-2 inclusion
Stage III, IV, or recurrent EC (endometrioid, serous, or CC), measurable disease
MITO END-2 arms
Control: Carbo 5AUC+ taxol 175
Exp: C/T + bev 15mg/kg –> Q21 bev maintenance
Both arms 6-8 cyclesM
MITO END-2 results
C/T= 49, Bev= 47
60% recurrent, 50% G3, 15% serous or CC
-PFS 10.5mo (CT) vs 13.7mo (CTB) (SI)
-OS 29.7mo vs 40mo (SI)
MITO END-2 conclusion
Bev combined with carboplatin and taxol in advanced or recurrent EC failed to show significant increase in PFS
Keynote 775 aim
To compare the efficacy and safety of len/pem with physicians choice of doxorubicin or paclitaxel chemo
Keynote 775 inclusion
Advanced, recurrent, metastatic EC of any histology, dz progression after 1 prior platinum based chemo, no hx VEGF or PD1 meds, up to 2 lines prior CT, measurable dz
Keynote 775 Arms
control: doxorubicin 60 mg/m2 q3wks or taxol 80mg/m2 weekly
Exp: lenvima 20mg PO QD + pembro 200mg IV q3 weeks up to 35 doses of pembro
Keynote 775 results
n=827, pMMR=697, dMMR=130
pMMR–PFS 3.8mo (CT) vs 6.6 (LP)
pMMR– OS 12mo vs 17.4mo
Overall: PFS 3.8mo vs 7.2mo
Overall: OS 11.4mo vs 18.3mo
Response rate: 14.7% vs 31.9%
pMMR RR: 15.1% vs 30.3%
Keynote 775 conclusion
Treatment with len/pem led to significantly longer PFS and OS in the pMMR, and overall population
RUBY (part 1) Aim
To assess efficacy and safety of dostarlimab in combo with C/T in patients with primary advanced or recurrent EC
RUBY (P1) inclusion
primary advanced or recurrent stage IIIA-IIIC1 EC w/ measurable dz
IIIC2-IV EC regardless of measurable dz
primary advanced IIIC1 w/ UCS, CC, USC, or mixed histology regardless of measurable dz
RUBY (P1) arms
Control: C/T AUC 5 + Taxol 175 q3wk x 6C
Exp: as above + dostarlimab 500mg–> 1000mg q6wks up to 3 years maintenance
RUBY (P1) results
control=249, exp=245
18% stage 3, 33% stage 4, 47.8% recurrent
54.7% endometrioid, 20.6% serous, 8.9% UCS
PFS: 61.4% (dMMR) vs 15.7% (CT)
PFS: 36.1% (overall) vs 18.1% (CT)
OS: 71.3% (drug) vs 56% (placebo)
OS: dMMR 83.3% vs 58.7%
–pMMR PFS 28.4% (D) vs 18.8% (CT)
–pMMR OS 67.7% (D) vs 55.1% (CT) (SI)
RUBY (P1) conclusion
The combination of dostarlimab, carboplatin, and taxol significantly improved outcomes for patients with newly diagnosed primary advanced or recurrent EC, with substantial benefit seen in dMMR tumors
GY018 Aim
To evaluate standard chemo of C/T + pembro + pembro maintenance vs placebo
GY018 Inclusion
Advanced stage metastatic or recurrent endometrial of any histology (except UCS)
Stage III or IV (measurable dz)
hx RT or HT permitted
GY018 Arms
Control: Carbo 5AUC + taxol 175 x6C + placebo
Exp: C/T + pembro 200mg q3wks + 400mg q6 weeks up to 20 cycles
GY018 Results
dMMR: 70% lower risk of dz progression w/ pembro
pMMR: PFS 8.7mo (CT) vs 13.1mo (P)
GY018 conclusion
Incorporation of immunotherapy into first line treatment of patients with advanced or recurrent EC translates into improved oncologic outcomes regardless of histology or MMR status
