PDL1 testing in GU cancers
GU cancer
a. Adjuvant:
-Non muscle invasive BCG resistant bladder cancer: Keytruda in those who progressed on BCG and declined cystectomy. KEYNOTE 057. CR41%, Duration of response 16months.
-T3/T4 or node positive patients who did not get cisplatin Neoadjuvant and declined it post op or were ineligible, could go on to get nivolumab which showed improved DFS in all comers including PDL1>1%. Study Checkmate 274.
What group of patients should get adjuvant cisplatin after cystectomy and what is the benefit? T3/T4, N+ if no NACT, should get cisplatin based on a metaanalysis. HR 0.75. 3 yr OS benefit 9%.
b. Neoadjuvant: PURE-01 study showed 42% PT0 in patients with PDL1> 10% with keytruda. vast majority were cisplatin eligible. I would not change my practice based on this.
c. Metastatic:
-Front line single agent pembro or atezo if PDL1 positive only if patient not eligible for cisplatin ( FDA label) or carboplatin. Or progression in less than 12 months of neoadjuvant chemo.
Very important negative data for IO: pembro in combination with chemo front line did not show any survival benefit. Therefore combo therapy i.e IO +chemo front line not useful in metastatic urothelial.
Atezo: IMvigor 130: showed PFS benefit for atezo front line with chemo. OS data not mature
DANUBE: Durva with tremelimumab was suggestive of OS benefit but overall neg.
-Second line: the median OS is 6-7months after progression on a platinum based chemo. Keytruda HR 070, 30% improvement, 3 month improvement over chemo in PDL1 positive and negative patients.
d. Maintenance: in the first line after platinum chemo-->Avelumab ( JAVELIN) patients with locally advanced or metastatic urothelial carcinoma whose disease has not progressed after 4-6 cycles of first-line platinum-containing chemotherapy
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