GU trials - AF Flashcards
VESPER (Bladder)
Phase 3, JCO 2022, NEOADJUVANT
P - Nonmetastatic muscle-invasive bladder cancer
I- 6 cycles ddMVAC (methotrexate, vinblastine, doxorubicin, cisplatin) q 2 weeks neoadjuvantly or adjuvantly
C - 4 cycles GC (cisplatin, gemcitabine)
O- Organ-confined response (less than ypT3, N0) was observed more frequently
with ddMVAC than GC (77% vs. 63%). PFS at 3 years was also significantly higher among those who received neoadjuvant ddMVAC (66% vs. 56%, HR 0.7). A
higher pCR rate for neoadjuvant ddMVAC than GC (42% vs. 36%). Reported
toxicity was similar, at around 50%. Grade 3 or higher AEs that were more
frequently observed with ddMVAC included gastrointestinal disorders (P = .003)
and asthenia (P = .001).
CheckMate 274 (Bladder)
Phase 3, NEJM 2021, ADJUVANT
P - MIBC patients who received cisplatin-based NAT with ypT2-ypT4a or ypN+ OR cisplatin ineligible or refused cisplatin-based NAT
I - Nivolumab 240mg IV q 2 weeks x 1 year
C - Placebo q 2 weeks
O- DFS (Primary), ITT - 20.8m v. 10.8m. Rate @ 6m - 74.9% v. 60.3% (HR 0.7, p <0.001).
DFS Rate PD-L1 > 1%: 74.5% v 55.7% (HR 0.55, P<0.001). Gr. 3 AEs 17.9% in Nivo group.
POUT (Upper Tract UC)
Phase 3, Lancet 2020, ADJUVANT
P - pT2-4 or N1-3, M0 UTUC post nephroureterectomy
I - Adjuvant gem + cis/carbo within 90 days of surgery
C - Surveillance
O - 3- year DFS (Primary): 71% v . 46% (HR 0.45, p = 0.0001). 44% Gr. 3 AEs, typical for regimen. Not powered for OS.
Javelin 100 (Bladder)
Phase 3, NEJM 2020, FIRST-LINE MAINTENANCE
P - Unresectable or metastatic UC who did not have disease progression with first-line chemotherapy
I - Avelumab 10mg/kg IV q 2 weeks
C - BSC
O - Median OS in ITT @ 3 years follow up (Primary) - 24m v. 15m (HR 0.76). PD-L1+ mOS: 31m v. 19m (HR 0.69)
Von der Masse (Bladder)
Phase 3, JCO 2000, First-line metastatic
P – Metastatic bladder cancer, previously untreated (N=405)
I – GC (gemcitabine 1,000 mg/m2 days 1, 8, and 15; cisplatin 70 mg/m2 day 2) 3 week cycle
C – MVAC (methotrexate 30 mg/m2 on days 1, 15, and 22; vinblastine 3 mg/m2 on days 2, 15, and 22; doxorubicin 30 mg/m2 on day 2; and cisplatin 70 mg/m2) 4 week cycle
O:
○ No significant differences in outcomes with GC vs MVAC
○ Patients experienced less weight loss, better performance status and less
fatigue with GC compared to MVAC as well as less serious toxicity
including neutropenia, neutropenic sepsis and mucositis
Keynote 045 (Bladder)
Phase 3, NEJM 2017, Second-line metastatic
P – Metastatic bladder cancer after progression on platinum-based
chemotherapy. No prior IO therapy. (N=542)
I – Pembrolizumab (200mg every 3 weeks) for up to 2 years.
C – Dealer’s choice chemo (paclitaxel, docetaxel, vinflunine)
O:
○ Improved mOS = 10.1 v 7.3 months (HR 0.70)
○ Similar mPFS = 2.1 v 3.3 months (HR 0.96)
EV301 (Bladder)
Phase 3, NEJM 2021, 3rd-line metastatic
P – Phase III, locally advanced or metastatic urothelial carcinoma who had previously received platinum-containing chemotherapy and had disease progression during or after treatment with a PD-1 or PD-L1 inhibitor (3rd line) (N=608)
I – EV (1.25 mg/kg on days 1, 8, 15 of 28-day cycle)
C – Dealer’s choice chemo (paclitaxel, docetaxel, vinflunine)
O – mOS 12.9 vs. 9.0 months; HR 0.70
○ PFS 5.6 vs 3.7 months, HR 0.6
○ Toxicity: peripheral neuropathy, rash, hyperglycemia
BLC2001 (Bladder)
Phase 2, NEJM 2019, Second/Third-line metastatic
P – FGFR 2/3 mutation+, PD after at least one course of chemotherapy (or within 12 months of adjuvant/neoadjuvant chemotherapy). Prior immunotherapy was allowed. (N=99)
I – Erdafitinib (8mg/day, continuously)
C – none (phase II)
O:
○ 40% ORR o mPFS 5.5 months, mOS 13.8 months
○ SE: hyperphosphatemia, hyponatremia, stomatitis, GI, LE, cytopenia, paronychia, central serous retinopathy, arrhythmia
■ Require ophthalmology baseline (and on study had ophtho exams
monthly)
■ Patients need to be on a low Phosphate diet
TROPHY-U-01 (Bladder)
Phase 2, JCO 2021, 3rd-line
P – Patients with advanced urothelial carcinoma, previously treated with
platinum-based chemotherapy and immunotherapy (N= 113)
I – Sacituzumab Govitecan 10mg/kg (days 1 and 8 every 21 days)
C – none (phase II)
O:
○ ORR 27%
○ mPFS = 5 months
○ mOS = 11 months
○ AE: neutropenia, anemia, diarrhea, febrile neutropenia
KEYNOTE 564 (RCC)
Phase 3, NEJM 2021, ADJUVANT
P - Locoregional clear cell RCC, nephrectomy <= 12w prior. 3 risk categories of patients:
■ Int/high risk (pT2, nuclear grade 4, sarcomatoid or cc, N0/M0 OR
pT3 any grade, N0/M0); ~86% of patients in this trial
■ High risk (pT4 any grade, N0/M0 OR any T any grade, N+/M0);
~8% of patients in this trial
■ M1 with NED after primary tumor and soft tissue metastases were
completely resected <1 year from nephrectomy; ~6% of patients in trial.
I - Pembro 200mg IV q 3w up to 1 year
C- placebo
O- Median DFS NR v NR HR 0.68
24m DFS rate 77.3% v 68.1% across all 3 risk categories
mOS NR v NR HR 0.54. 24m OS 96.6% v 93.5%
Gr. 3 tox rate of 32% v 17.7%
S-TRAC (RCC)
Phase 3, NEJM 2016, ADJUVANT
P- locoregional higher risk ccRCC (stage ≥3, regional LN+, or both), no
previously treatment, R0/R1 resection and no metastases post
nephrectomy
I- sunitinib (50 mg PO daily 4 weeks on, 2 weeks off) x1 year
C- placebo
O
■ Primary
● Median DFS 6.8 vs 5.6 yrs, HR 0.76 (sig)
● 3 yr DFS rates 64.9% vs 59.5%
■ Secondary
● Investigator assessed median DFS 6.5 vs 4.5 yrs, HR 0.81
(NOT sig)
○ Investigators called relapse earlier than BICR more
often in patients on sunitinib vs placebo
● OS data were immature, but HR 1.01
● TRAE 99.7% vs 88.5%
LITESPARK-004 (VHL-RCC)
Phase 2, NEJM 2021, Early-stage
P - Germline VHL alteration with at least one measurable RCC tumour. None greater than 3cm necessitating immediate surgical intervention.
I - Belzutifan 120mg PO daily
C- N/A
O- ORR in RCC tumours
- Median exposure 21m
- ORR 49% (30 partial response)
- 30 pts stable disease
- 2 progressive
- 24m PFS 96%
- AE = anemia, fatigue, H/A, dizziness, 9 patients Gr 3 + TRAE
- Unique toxicity of belzutifan = HYPOXIA, stop if SpO2 < 92%
Cytoreductive nephrectomy in mRCC
Phase 3, NEJM 2018, METASTATIC
P- ccRCC with metastatic disease, be a surgical candidate for
nephrectomy and eligible for sunitinib
I- sunitinib 50 mg PO daily, 4 weeks on, 2 weeks off (no nephrectomy)
C- nephrectomy followed by sunitinib (as above, started 3-6 weeks
post-surgery)
O-
■ Primary
● mOS 18.4 vs 13.9 mos, HR 0.89, NOT sig
● Updated analysis- mOS 19.8 mos vs 15.6 mos, HR 0.97,
NON-INFERIOR
○ intermediate risk- mOS 23.9 vs 13.3 mos
○ poor risk mOS 19 vs 10.2 mos
■ Secondary
● mPFS 8.3 vs 7.2 mos, HR 0.82 ORR 29.1% vs 27.4%
CheckMate 214 (RCC)
Phase 3, NEJM 2018, First-line metastatic
P- previously untreated ccRCC, KPS ≥70, excluded if CNS mets, ICI
contraindications or taking GC/immunosuppressed
I- nivolumab 3 mg/kg + ipilimumab 1 mg/kg q3 weeks x4 🡪 nivolumab
maintenance at 3 mg/kg q2 weeks
C- sunitinib 50 mg PO daily (4 weeks on, 2 weeks off)
O- Int/Poor Risk: ORR 42% v 26% (CR 10% v 1.4%). Sarcomatoid ORR 60%
mPFS 11.6m v 8.4m HR 0.82 (HR 0.75 @ 42m update)
mOS NR v 26m HR 0.63 (HR 0.66 @ 42m update)
Favourable Risk: mOS favoured sunitinib (HR 1.45)
Gr3/4 46% v 63%
Keynote 426 (RCC)
Phase 3, NEJM 2019, First-line metastatic
P- previously untreated advanced ccRCC. Excluded if uncontrolled HTN,
contraindications to ICI, immunosuppression, CHF or history of an ischemic event
■ ~30% were favorable, ~56% intermediate and ~13% poor risk
■ PDL1 CPS ≥1 in ~60% of patients
I- pembrolizumab 200 mg IV q3 weeks (max 35 cycles) + axitinib 5 mg PO BID
C- sunitinib 50 mg PO daily, 4 weeks on, 2 weeks off
O- Primary
mOS NR vs NR 🡪 42 mos update 45.7 vs 40.1 mos, HR
0.73 (sig)
42 mos OS rates 57.5% vs 48.5% (I vs C), HR 0.53, sig
ORR 60% v 40%
Benefit seen across all risk groups regardless of PD-L1 CPS
Gr3+ AE 76% v 71%
CheckMate 9ER (RCC)
Phase 3, NEJM 2021, First-line metastatic
P- advanced ccRCC, previously untreated, all IMDC risk groups
■ Excluded if >10 mg/day prednisone equivalents or other
immunosuppression within 14 days of randomization, and
contraindications to ICI
■ ~22% favorable, ~58% intermediate and ~20% poor risk
■ 75% had PDL1 TPS <1%
I- nivolumab 240 mg IV q 2 weeks (max 2 years) + cabozantinib 40 mg PO daily
C- sunitinib 50 mg PO daily, 4 weeks on, 2 weeks off
O-
■ Primary
● mPFS 16.6 vs 8.3 mos, HR 0.51, sig
■ Secondary
● mOS HR: 0.70
● mOS 37.7 vs 34.3 mo
● ORR 56% vs 28%
■ Benefit was present across all subgroups and PDL1 statuses (and
whether or not there were bone metastases)
■ Grade 3+ AE 65% vs 54%
