Bladder articles

Question 1

BCa Lit

EV 302

6

Answer 1

• EV+ P improves OS by 15 months in untreated UC
• Enfortumab is a antibody to Nectin-4 and vedotin is a payload drug
• RCT 886pts with unresectable for locally advanced UC +/- M1
• EV+ P vs G/C or Gem/Carbo
• mOS 31.5 vs 16.1 months, PFS 12.5 vs 6.3 months
• 67% ORR and 29% CR

JCO 2024

Powles, Thomas et al. “Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer.” The New England journal of medicine vol. 390,10 (2024): 875-888. doi:10.1056/NEJMoa2312117

Question 2

BCa lit

RAZOR

4

Answer 2

• Robotic cystectomy is non-inferior to open cystectomy
• RCT 350 pts; open vs robotic RC
• 2y PFS was 72%
• AEs in 69% vs 67% (UTI and Ileus)

Lancet 2018

Question 3

BCa lit

SWOG 8710

Answer 3

• NAC MVAC before RC improves OS
• Occult micrometastases are a major problem, 7 negative NAC trials
• RCT 300 pts with cN0M0 with RC vs NAC MVAC
• 38% pT0, 5y OS 57% vs 43%
• ~33% pre-op AEs, no change in post-op AEs

NEJM 2003

Question 4

BCa lit

VESPER

4

Answer 4

• ddMVAC vs Gem/Cis as peri-op chemo for MIBC
• RCT 500 pts; ddMVAC vs G/C (88% NAC)
• ypT0 42% vs 36% for ddMVAC
• similar toxicity but GI and fatigue were worse with ddMVAC

JCO 2020

Question 5

BCa lit

IMvigor 210

4

Answer 5

• Atezolizumab for cis-ineligible pts with advanced UC
• Single arm Phase 2, 123 pts
• ORR 23%, CR 9%
• mOS 16m

Lancet 2017

Question 6

BCa lit

KEYNOTE 052

4

Answer 6

• Pembro is first line for cis-ineligible pts with advanced UC
• Single arm Phase 2, 370 pts
• ORR 24%, CR 20%
• mOS 11.3m

Lancet Onc 2017

Question 7

BCa lit

KEYNOTE 045

5

Answer 7

• Pembro is option for progression through platinum chemo
• RCT 542 pts with advanced US that progressed or recurred after platinum
• Pembro vs 2nd line chemo
• OS 10m vs 7m, higher if PDl-1 score over 10%
• fewer AEs

NEJM 2017

Question 8

BCa lit

BLC 2001

4

Answer 8

• Erdafitinib is option for progression through chemo +/- ICI
• Alterations in FGFR may be associated with lower sensitivity to ICI
• Phase 2, 99pts with progression AND alterations of FGFR gene
• 40% ORR, mOS 14m

NEJM 2019

Question 9

BCa lit

JAVELIN Bladder

Answer 9

• Avelumab maintenance prolongs survival after G/C for advanced US
• RCT 700 pts with advanced or unresectable UC (SD during G/C)
• Avelumab maintenance vs observation
• OS at 1y 71 vs 58% with 60% in PDL1 pts

NEJM 2020

Question 10

BCa lit

EV 301

6

Answer 10

• EV improves OS by 4 months in UC that progressed through chemo and ICI
• Enfortumab is a antibody to Nectin-4 and vedotin is a payload drug
• RCT 608pts with unresectable for locally advanced UC +/- M1
• EV vs additional chemo
• mOS 13 vs 9 months, PFS 3.7 vs 2 months
• 44% ORR and 12% CR

NEJM 2021

Question 11

BCa lit

CheckMate 274

5

Answer 11

• Adjuvant Nivolumab improved DFS after RC +/- NAC for MIBC
• RCT 709 pts with MIBC s/p RC (44% NAC)
• Adjuvant nivo vs placebo
• mDFS 21 vs 11m with 6m DFS 75 vs 60%
• G3 AEs 18 vs 7% with 2 ICI deaths

NEJM 2021

Question 12

BCa lit

IMvigor 010

6

Answer 12

• Adjuvant atezolizumab only improved DFS and OS in HR pts with ctDNA after RC or NUx
• RCT 809 HRpts with UC s/p RC or NUx +/- NAC
• adjuvant atezolizuman vs placebo
• negative trial
• 214pts with ctDNA mDFS 5.9 vs 4.4 and mOS 26 vs 16
• first trial to used ctDNA as biomarker for adjuvant therapy

Nature 2021