SACT Flashcards
Management of metastatic endometrial cancer?
Endocrine is preferred for low-grade slowly progressive disease. Repeat biopsies to confirm receptor status if recurrence. Progestogens (medroxyprogesterone acetate 200-300mg and megestrol acetate 160mg) are recommended.
Alternatives: AI; tamoxifen; fulvesterant.
Endocrine treatment results in response rates of 55%, with: slow growing/ HR+ patients/long interval between relapse being good prognostic factors for response to hormones.
Further treatment depends on MMR status.
pMMR: 1st + 2nd line Carbo/Taxol and Len/Pem. Then either weekly paclitaxel or caelyx or rechallenge platinum
dMMR: 1st line: Dostarlimab + Carbo/Taxol, or Len/Pem.
2nd line: Dostarlimab, or Pembro, or Len/Pem (whichever hasn’t been used yet.).
3rd line: Carbo/Caelyx, Caelyx, weekly paclitaxel, or Carbo/Taxol (if not yet used in metastatic/advanced setting).
Rechallenge platinum doublet viable option (interval > 6 months)
Stage IA - pelvic nodes 6-9%; 5yr OS 90%
Stage IB - G1 10% pelvic nodes; G3 15%; 5yr OS 81%
Stage II - 20% nodes; 5yr OS 66%
Stage IIIA - 71% nodes; 5yr OS 60%
Stage IIIB - 57% nodes: 5yr OS 52%
Stage IIIC1 - 5yr OS 52%
Stage IIIC2 - 5yr OS 40%
Stage IVA - 5yr OS 17%
Management of metastatic cervical cancer?
First line: Pembro (If CPS >1, look at KM below) + paclitaxel 175mg/m2 + carboplatin AUC5 (consider 6 if GFR>60) 3 weekly x6 + bevacizumab 15mg/kg 3 weekly (no maintenance). Don’t give bevacizumab if bowel obstruction. Smoking increases risk, recommend cessation.
In trial, carbo/taxol had the highest response rate (29%, PFS 5.8 months, OS 12.8 months) amongst chemo agents (prior to advent of bev).
Second line: topotecan 0.75mg/m2 D1-3 + cisplatin 50mg/m2 D1 3 weekly x6 or to PD
Relevant trials:
GOG-240: adding Bev to platinum doublet. PFS extended, 16.8 vs 13.3 months. More hypertension, more VTE and more fistulas >G2 (8.6% vs 1%)
Keynote 526, Pembro + standard vs standard (bev included at physicians discretion). PFS 10 vs 8 months in CPS-1, 53% vs 47% alive at 28 months
Stage IA1 - 5yr OS 100%
Stage IB1 - 5yr OS 85-90%
Stage IB2 - 5yr OS 85-90%
Stage IIA1-2 - 5yr OS 85-90%
Stage IIB - 5yr OS 75%
Stage IIIA - 5yr OS 70-75%
Stage IIIB - 5yr OS 50-70%
Stage IVA - 5yr OS 20-40%
Stage IVB - 5yr OS 5-10%
Management of ca cervix in pregnant women (1st trimester)?
1) Carbo/taxol (safe in pregnancy)
2) Vaginal delivery c/i (risk of haemorrhage, perforation, infection and disease being implanted in the episiotomy scar) > C-Section
metastatic vaginal cancer?
First line: paclitaxel 175mg/m2 + carboplatin AUC5 (consider 6 if GFR>60) 3 weekly x6
5 year Stage IV survival 25%
Management of metastatic bladder ca?
First-line: cisplatin or carboplatin/gemcitabine then maintenance avelumab 10mg/kg 2 weekly for up to 5 years - OS 21.4m vs 14 (JAVELIN bladder 100 study, chemo vs chemo + maintenance IO).
Second line: atezoliumab 1200mg 3 weekly first line if PD-L1 >5%) or 1680mg 4 weekly. Based on inferiority in IMvigor 130.
Third line: paclitaxel/carboplatin or gemcitabine
EV-302 / KEYNOTE A39. EV (enfortumab-vedotin, directed against nectin-4, Antibody-drug conjugate) + pembro VS carbo/cis combination chemo. PFS 12 vs 6, OS 31 vs 16. New SOC internationally.
How is castration-resistant (progressive on ADT), non-metastatic (ie no visible disease) managed?
Apalutamide or daralutamide: Darolutamide 600mg od (3yr OS 83% vs. 77%), or Apalutamide 240mg od (SPARTAN trial). PSAdt <10months to be eligible.
How is castration-sensitive, metastatic prostate cancer managed?
Options:
1) enzalutamide + ADT (ENZAmet trial)
2) triplet therapy if well (docetaxel, daralutamide and ADT): ARASENS trial
3) ADT alone
4) BSC
How does one manage castrate-resistant, metastatic prostate cancer?
1) Enzalutamide + ADT (ENZAMET trial)
2) Abiraterone + olaparib + ADT if not well enough for ARSI (PROpel trial,
3) Palliative XRT 55 Gy in 20 fractions in low volume disease (STAMPEDE (2018): Newly diagnosed metastatic prostate cancer. ADT/ADT+docetaxel +/- prostate RT 55Gy/20# or 36Gy/6# weekly. For all-comers no improvement in OS. For low metastatic burden 3yr OS 73% vs. 81% with RT.)
4) Docetaxel, cabazitaxel and Radium-223 (remember that visceral mets are contraindicated, and to stop abiraterone for risk of fractures) are other options
Management of low or intermediate IMDC score renal cancer?
IMDC score: a point each for:
- <1 year since progression
- raised platelets
- raised neutrophils
- raised calcium
- KPS <80
- Hb <120
Low risk:
- sunitinib OR Avelumab/Axitinib
-2nd line cabozantinib or tivozanib or everolimus / lenvatinib
IMDC intermediate/poor renal cancer?
1st line:
- len/pen
-ipi/nivo
- cabozantinib/ nivolumab
2nd line:
- cabozantinib/sunitinib/tivozanib
Management of metastatic melanoma?
BRAF V600 mutation? (oncogene hyperactivated will trigger the RAF-MEK-ERK pathway)
1st: Dab (BRAF-inhibitor) +Tram (MEK inhibitor) / enco + bini > combination reduces b-raf driven toxicity like cSCC and also reduces paradoxical hyperactivation/resistance through MEK pathway
2nd: Ipi (CTLA-4 inhibitor) /Nivo vs Pembro (PD-1 inhibitor) vs Nivolumab (PD-1 inihibitor) + Relatlimab (LAG-3 inhibition)
BRAF WT?
Same as above, just skip the dab/tram step
management of metastatic cutaneous SCC?
1) Cemiplimab (PD-1 inhibitor) 3 weekly for up to 24 months (~50% RR, 16% complete response)
2) Cis/5-FU second-line
When does thyroid ca (glandular) become iodine-refractory?
-Disease that does not take up radioiodine
-Disease that loses avidity for radioiodine
-Disease with mixed uptake of radioiodine
-Disease with iodine avidity but continues to progress
-FDG avid disease
Important as significantly reduced 10 year survival rates in advanced DTC.
-Iodine avid: 60% vs lodine non-avid: 10%
- median survival once iodine refractory 3-5 yrs
It is worth checking iodine refractory status
-adequate preparation with sufficiently raised TSH, low iodine diet, iv contrast agents
How is iodine-refractory thyroid ca managed?
Sorafenib (DECISION trial), PFS 10.8 months vs placebo
Lenvatinib (SELECT trial), 18 months vs 3 placebo
Genetics: NTRK (larotrectinib), BRAF (dabrafenib), RET (pralsetinib/selpercatinib) testing for targeted therapies
management of metastatic anaplastic thyroid cancer?
Bloods including NM GFR
No role for RAI/TSH suppression
BRAF wt: First line carboplatin AUC 5/paclitaxel 175mg/m2 3 weekly. PFS benefit. Response in 10-15%.
BRAF mt: Dabrafenib 150mg bd and trametinib 2mg od continuous. Pyrexia, retinal pigment epithelial dystrophy , pneumonitis, decreased LVEF
management of metastatic medullary thyroid ca?
First line: cabozantinib 140mg od continuous. Diarrhoea is common. PPE. Can get long QT. ECG pre-treatment. BP. Urine dip - proteinuria.
